Moderna vaccine
Study Shows Benefits of COVID-19 Vaccines and Boosters
Posted on by Lawrence Tabak, D.D.S., Ph.D.
As colder temperatures settle in and people spend more time gathered indoors, cases of COVID-19 and other respiratory illnesses almost certainly will rise. That’s why, along with scheduling your annual flu shot, it’s now recommended that those age 5 and up should get an updated COVID-19 booster shot [1,2]. Not only will these new boosters guard against the original strain of the coronavirus that started the pandemic, they will heighten your immunity to the Omicron variant and several of the subvariants that continue to circulate in the U.S. with devastating effects.
At last count, about 14.8 million people in the U.S.—including me—have rolled up their sleeves to receive an updated booster shot [3]. It’s a good start, but it also means that most Americans aren’t fully up to date on their COVID-19 vaccines. If you or your loved ones are among them, a new study may provide some needed encouragement to make an appointment at a nearby pharmacy or clinic to get boosted [4].
A team of NIH-supported researchers found a remarkably low incidence of severe COVID-19 illness last fall, winter, and spring among more than 1.6 million veterans who’d been vaccinated and boosted. Severe illness was also quite low in individuals without immune-compromising conditions.
These latest findings, published in the journal JAMA, come from a research group led by Dan Kelly, University of California, San Francisco. He and his team conducted their study drawing on existing health data from the Veterans Health Administration (VA) within a time window of July 2021 and May 2022.
They identified 1.6 million people who’d had a primary-care visit within the last two years and were fully vaccinated for COVID-19, which included receiving a booster shot. Almost three-quarters of those identified were 65 and older. Nearly all were male, and more than 70 percent had another pre-existing health condition that put them at greater risk of becoming seriously ill from a COVID-19 infection.
Over a 24-week follow-up period for each fully vaccinated individual, 125 per 10,000 people had a breakthrough infection. That’s about 1 percent. Just 8.9 in 10,000 fully vaccinated people—less than 0.1 percent—died or were hospitalized from COVID-19 pneumonia. Drilling down deeper into the data:
• Individuals with an immune-compromising condition had a very low rate of hospitalization or death. In this group, 39.6 per 10,000 people had a serious breakthrough infection. That translates to 0.3 percent.
• For people with other preexisting health conditions, including diabetes and heart disease, hospitalization or death totaled 0.07 percent, or 6.7 per 10,000 people.
• For otherwise healthy adults aged 65 and older, the incidence of hospitalization or death was 1.9 per 10,000 people, or 0.02 percent.
• For boosted participants 65 or younger with no high-risk conditions, hospitalization or death came to less than 1 per 10,000 people. That comes to less than 0.01 percent.
It’s worth noting that these results reflect a period when the Delta and Omicron variants were circulating, and available boosters still were based solely on the original variant. Heading into this winter, the hope is that the updated “bivalent” boosters from Pfizer and Moderna will offer even broader protection as this terrible virus continues to evolve.
The Centers for Disease Control and Prevention continues to recommend that everyone stay up to date with their COVID-19 vaccines. That means all adults and kids 5 and older are encouraged to get boosted if it has been at least two months since their last COVID-19 vaccine dose. For older people and those with other health conditions, it’s even more important given their elevated risk for severe illness.
What if you’ve had a COVID-19 infection recently? Getting vaccinated or boosted a few months after you’ve had a COVID-19 infection will offer you even better protection in the future.
So, if you are among the millions of Americans who’ve been vaccinated for COVID-19 but are now due for a booster, don’t delay. Get yourself boosted to protect your own health and the health of your loved ones as the holidays approach.
References:
[1] CDC recommends the first updated COVID-19 booster. Centers for Disease Control and Prevention. September 1, 2022.
[2] CDC expands updated COVID-19 vaccines to include children ages 5 through 11. Centers for Disease Control and Prevention, October 12, 2022.
[3] COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention.
[4] Incidence of severe COVID-19 illness following vaccination and booster with BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Kelly JD, Leonard S, Hoggatt KJ, Boscardin WJ, Lum EN, Moss-Vazquez TA, Andino R, Wong JK, Byers A, Bravata DM, Tien PC, Keyhani S. JAMA. 2022 Oct 11;328(14):1427-1437.
Links:
COVID-19 Research (NIH)
Dan Kelly (University of California, San Francisco)
NIH Support: National Institute of Allergy and Infectious Diseases
How COVID-19 Immunity Holds Up Over Time
Posted on by Lawrence Tabak, D.D.S., Ph.D.
More than 215 million people in the United States are now fully vaccinated against the SARS-CoV-2 virus responsible for COVID-19 [1]. More than 40 percent—more than 94 million people—also have rolled up their sleeves for an additional, booster dose. Now, an NIH-funded study exploring how mRNA vaccines are performing over time comes as a reminder of just how important it will be to keep those COVID-19 vaccines up to date as coronavirus variants continue to circulate.
The results, published in the journal Science Translational Medicine, show that people who received two doses of either the Pfizer or Moderna COVID-19 mRNA vaccines did generate needed virus-neutralizing antibodies [2]. But levels of those antibodies dropped considerably after six months, suggesting declining immunity over time.
The data also reveal that study participants had much reduced protection against newer SARS-CoV-2 variants, including Delta and Omicron. While antibody protection remained stronger in people who’d also had a breakthrough infection, even that didn’t appear to offer much protection against infection by the Omicron variant.
The new study comes from a team led by Shan-Lu Liu at The Ohio State University, Columbus. They wanted to explore how well vaccine-acquired immune protection holds up over time, especially in light of newly arising SARS-CoV-2 variants.
This is an important issue going forward because mRNA vaccines train the immune system to produce antibodies against the spike proteins that crown the surface of the SARS-CoV-2 coronavirus. These new variants often have mutated, or slightly changed, spike proteins compared to the original one the immune system has been trained to detect, potentially dampening the immune response.
In the study, the team collected serum samples from 48 fully vaccinated health care workers at four key time points: 1) before vaccination, 2) three weeks after the first dose, 3) one month after the second dose, and 4) six months after the second dose.
They then tested the ability of antibodies in those samples to neutralize spike proteins as a correlate for how well a vaccine works to prevent infection. The spike proteins represented five major SARS-CoV-2 variants. The variants included D614G, which arose very soon after the coronavirus first was identified in Wuhan and quickly took over, as well as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529).
The researchers explored in the lab how neutralizing antibodies within those serum samples reacted to SARS-CoV-2 pseudoviruses representing each of the five variants. SARS-CoV-2 pseudoviruses are harmless viruses engineered, in this case, to bear coronavirus spike proteins on their surfaces. Because they don’t replicate, they are safe to study without specially designed biosafety facilities.
At any of the four time points, antibodies showed a minimal ability to neutralize the Omicron spike protein, which harbors about 30 mutations. These findings are consistent with an earlier study showing a significant decline in neutralizing antibodies against Omicron in people who’ve received the initial series of two shots, with improved neutralizing ability following an additional booster dose.
The neutralizing ability of antibodies against all other spike variants showed a dramatic decline from 1 to 6 months after the second dose. While there was a marked decline over time after both vaccines, samples from health care workers who’d received the Moderna vaccine showed about twice the neutralizing ability of those who’d received the Pfizer vaccine. The data also suggests greater immune protection in fully vaccinated healthcare workers who’d had a breakthrough infection with SARS-CoV-2.
In addition to recommending full vaccination for all eligible individuals, the Centers for Disease Control and Prevention (CDC) now recommends everyone 12 years and up should get a booster dose of either the Pfizer or Moderna vaccines at least five months after completing the primary series of two shots [3]. Those who’ve received the Johnson & Johnson vaccine should get a booster at least two months after receiving the initial dose.
While plenty of questions about the durability of COVID-19 immunity over time remain, it’s clear that the rapid deployment of multiple vaccines over the course of this pandemic already has saved many lives and kept many more people out of the hospital. As the Omicron threat subsides and we start to look forward to better days ahead, it will remain critical for researchers and policymakers to continually evaluate and revise vaccination strategies and recommendations, to keep our defenses up as this virus continues to evolve.
References:
[1] COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention. February 27, 2022.
[2] Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection. Evans JP, Zeng C, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Sci Transl Med. 2022 Feb 15:eabn8057.
[3] COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Feb 2, 2022.
Links:
COVID-19 Research (NIH)
Shan-Lu Liu (The Ohio State University, Columbus)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Heart, Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development
Accelerating COVID-19 Vaccine Testing with ‘Correlates of Protection’
Posted on by Dr. Francis Collins
With Omicron now on so many people’s minds, public health officials and virologists around the world are laser focused on tracking the spread of this concerning SARS-CoV-2 variant and using every possible means to determine the effectiveness of our COVID-19 vaccines against it. Ultimately, the answer will depend on what happens in the real world. But it will also help to have a ready laboratory means for gauging how well a vaccine works, without having to wait many months for the results in the field.
With this latter idea in mind, I’m happy to share results of an NIH-funded effort to understand the immune responses associated with vaccine-acquired protection against SARS-CoV-2 [1]. The findings, based on the analysis of blood samples from more than 1,000 people who received the Moderna mRNA vaccine, show that antibody levels do correlate, albeit somewhat imperfectly, with how well a vaccine works to prevent infection.
Such measures of immunity, known as “correlates of protection,” have potential to support the approval of new or updated vaccines more rapidly. They’re also useful to show how well a vaccine will work in groups that weren’t represented in a vaccine’s initial testing, such as children, pregnant women, and those with certain health conditions.
The latest study, published in the journal Science, comes from a team of researchers led by Peter Gilbert, Fred Hutchinson Cancer Research Center, Seattle; David Montefiori, Duke University, Durham, NC; and Adrian McDermott, NIH’s Vaccine Research Center, National Institute of Allergy and Infectious Diseases.
The team started with existing data from the Coronavirus Efficacy (COVE) trial. This phase 3 study, conducted in 30,000 U.S. adults, found the Moderna vaccine was safe and about 94 percent effective in protecting people from symptomatic infection with SARS-CoV-2 [2].
The researchers wanted to understand the underlying immune responses that afforded that impressive level of COVID-19 protection. They also sought to develop a means to measure those responses in the lab and quickly show how well a vaccine works.
To learn more, Gilbert’s team conducted tests on blood samples from COVE participants at the time of their second vaccine dose and again four weeks later. Two of the tests measured concentrations of binding antibodies (bAbs) that latch onto spike proteins that adorn the coronavirus surface. Two others measured the concentration of more broadly protective neutralizing antibodies (nAbs), which block SARS-CoV-2 from infecting human cells via ACE2 receptors found on their surfaces.
Each of the four tests showed antibody levels that were consistently higher in vaccine recipients who did not develop COVID-19 than in those who did. That is consistent with expectations. But these data also allowed the researchers to identify the specific antibody levels associated with various levels of protection from disease.
For those with the highest antibody levels, the vaccine offered an estimated 98 percent protection. Those with levels about 1,000 times lower still were well protected, but their vaccine efficacy was reduced to about 78 percent.
Based on any of the antibodies tested, the estimated COVID-19 risk was about 10 times lower for vaccine recipients with antibodies in the top 10 percent of values compared to those with antibodies that weren’t detectable. Overall, the findings suggest that tests for antibody levels can be applied to make predictions about an mRNA vaccine’s efficacy and may be used to guide modifications to the current vaccine regimen.
To understand the significance of this finding, consider that for a two-dose vaccine like Moderna or Pfizer, a trial using such correlates of protection might generate sufficient data in as little as two months [3]. As a result, such a trial might show whether a vaccine was meeting its benchmarks in 3 to 5 months. By comparison, even a rapid clinical trial done the standard way would take at least seven months to complete. Importantly also, trials relying on such correlates of protection require many fewer participants.
Since all four tests performed equally well, the researchers say it’s conceivable that a single antibody assay might be sufficient to predict how effective a vaccine will be in a clinical trial. Of course, such trials would require subsequent real-world studies to verify that the predicted vaccine efficacy matches actual immune protection.
It should be noted that the Food and Drug Administration (FDA) would need to approve the use of such correlates of protection before their adoption in any vaccine trial. But, to date, the totality of evidence on neutralizing antibody responses as correlates of protection—for which this COVE trial data is a major contributor—is impressive.
Neutralizing antibody levels are also now being considered for use in future coronavirus vaccine trials. Indeed, for the EUA of Pfizer’s mRNA vaccine for 5-to-11-year-olds, the FDA accepted pre-specified success criteria based on neutralizing antibody responses in this age group being as good as those observed in 16- to 25-year-olds [4].
Antibody levels also have been taken into consideration for decisions about booster shots. However, it’s important to note that antibody levels are not precise enough to help in deciding whether or not any particular individual needs a COVID-19 booster. Those recommendations are based on how much time has passed since the original immunization.
Getting a booster is a really good idea heading into the holidays. The Delta variant remains very much the dominant strain in the U.S., and we need to slow its spread. Most experts think the vaccines and boosters will also provide some protection against the Omicron variant—though the evidence we need is still a week or two away. The Centers for Disease Control and Prevention (CDC) recommends a COVID-19 booster for everyone ages 18 and up at least six months after your second dose of mRNA vaccine or two months after receiving the single dose of the Johnson & Johnson vaccine [5]. You may choose to get the same vaccine or a different one. And, there is a place near you that is offering the shot.
References:
[1] Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.
Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, Zhou H, Houchens CR, Martins K, Jayashankar L, Castellino F, Flach B, Lin BC, O’Connell S, McDanal C, Eaton A, Sarzotti-Kelsoe M, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Huynh C, Miller J, El Sahly HM, Baden LR, Baron M, De La Cruz L, Gay C, Kalams S, Kelley CF, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Carpp LN, Pajon R, Follmann D, Donis RO, Koup RA; Immune Assays Team§; Moderna, Inc. Team§; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team§; United States Government (USG)/CoVPN Biostatistics Team§. Science. 2021 Nov 23:eab3435.
[2] Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group. N Engl J Med. 2021 Feb 4;384(5):403-416.
[3] A government-led effort to identify correlates of protection for COVID-19 vaccines. Koup RA, Donis RO, Gilbert PB, Li AW, Shah NA, Houchens CR. Nat Med. 2021 Sep;27(9):1493-1494.
[4] Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. Walter EB, Talaat KR, Sabharwal C, Gurtman A, Lockhart S, Paulsen GC, Barnett ED, Muñoz FM, Maldonado Y, Pahud BA, Domachowske JB, Simões EAF, Sarwar UN, Kitchin N, Cunliffe L, Rojo P, Kuchar E, Rämet M, Munjal I, Perez JL, Frenck RW Jr, Lagkadinou E, Swanson KA, Ma H, Xu X, Koury K, Mather S, Belanger TJ, Cooper D, Türeci Ö, Dormitzer PR, Şahin U, Jansen KU, Gruber WC; C4591007 Clinical Trial Group. N Engl J Med. 2021 Nov 9:NEJMoa2116298.
[5] COVID-19 vaccine booster shots. Centers for Disease Control and Prevention. Nov 29, 2021.
Links:
COVID-19 Research (NIH)
Combat COVID (U.S. Department of Health and Human Services)
Peter Gilbert (Fred Hutchison Cancer Research Center)
David Montefiori (Duke University, Durham, NC)
Adrian McDermott (National Institute of Allergy and Infectious Diseases/NIH)
NIH Support: National Institute of Allergy and Infectious Diseases
Feeling Grateful This Thanksgiving for Biomedical Research
Posted on by Dr. Francis Collins
Yes, we can all agree that 2021 has been a tough year. But despite all that, Thanksgiving is the right time to stop and count our many blessings. My list starts with my loving wife Diane and family, all of whom have been sources of encouragement in these trying times. But also high up on the list this Thanksgiving is my extreme gratitude to the scientific community for all the research progress that has been made over the past 23 months to combat the pandemic and return our lives ever closer to normal.
Last year, we were busy learning how to celebrate a virtual Thanksgiving. This year, most of us are feeling encouraged about holding face-to-face gatherings once again—but carefully!—and coordinating which dishes to prepare for the annual feast.
The COVID-19 vaccines, developed by science in record time and with impressive safety and effectiveness, have made this possible. The almost 230 million Americans who have chosen to receive at least one dose of a COVID-19 vaccine have taken a critical step to protect themselves and others. They have made this season a much safer one for themselves and those around them than a year ago. That includes almost all adults ages 65 and up. While vaccination rates aren’t yet as high as they need to be in younger age groups, about 70 percent of Americans ages 12 and up are now fully vaccinated.
But with evidence that the effectiveness of the vaccines can wane over time and with the continued threat of the Delta variant, I was happy to see the recent approval by both FDA and CDC that all adults 18 and over are now eligible to receive a booster. That is, provided you are now more than 6 months past your initial immunization with the Moderna or Pfizer or 2 months past your immunization with the Johnson & Johnson vaccine. I recently got my Moderna booster and I’m glad for that additional protection. Don’t wait—the booster is the best way to defend against a possible winter surge.
Children age 5 and up are also now eligible to get the Pfizer vaccine, a development that I know brought a sense of relief and gratitude for many parents with school-aged children at home. It will take a little time for full vaccination of this age group. But more than 2.5 million young kids around the country already have rolled up their sleeves and have some immunity against COVID-19. These children are on track to be fully vaccinated before Christmas.
I’m also extremely grateful for all the progress that’s been made in treating COVID-19. Developing new treatments typically takes many years, if not decades. But NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) initiative, a public-private partnership involving 20 biopharmaceutical companies, academic experts, and multiple federal agencies, has helped lead the way to this rapid progress.
We’ve seen successes in the use of monoclonal antibodies and in the repurposing of existing drugs, such as blood thinning treatments, to keep folks hospitalized with COVID-19 from becoming severely ill and needing some form of organ support. Now it looks as though our hopes for safe and effective oral antiviral medicines to reduce the risk of severe illness in individuals just diagnosed with COVID-19 could soon be realized, too.
To combat COVID-19, rapid and readily accessible testing also is key, and NIH’s Rapid Acceleration of Diagnostics (RADx®) initiative continues to speed innovation in COVID-19 testing. RADx® also recently launched a simple online calculator tool to help individuals make critical decisions about when to get a test [1]. Meanwhile, a new initiative called Say Yes! COVID Test (SYCT) is exploring how best to implement home-testing programs in our communities.
More research progress is on the way. But, until the pandemic is history, please remember to stay safe this holiday season. The best way to do so is to get fully vaccinated [2]. As I noted above, most adults who got vaccinated earlier this year are now eligible for a booster shot to ensure they remain well protected. Go to vaccines.gov to find the site closest to you that can provide the shot.
The best way to protect young children who aren’t yet eligible or fully vaccinated and others who may be at higher risk is by making sure you and others around them are vaccinated. It’s still strongly recommended to wear a well-fitting mask over your nose and mouth when in public indoor settings, especially if there’s considerable spread of COVID-19 in your community.
If you are gathering with multiple households or people from different parts of the country, consider getting tested for COVID-19 in advance and take extra precautions before traveling. By taking full advantage of all the many scientific advances we’ve made over the last year, we can now feel good about celebrating together again this holiday season. Happy Thanksgiving!
References:
[1] When to Test offers free online tool to help individuals make informed COVID-19 testing decisions. National Institutes of Health. November 3, 2021.
[2] Safer ways to celebrate holidays. Centers for Disease Control and Prevention. October 15, 2021.
Links:
COVID-19 Research (NIH)
Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) (NIH)
Rapid Acceleration of Diagnostics (RADx®) (NIH)
When To Test (Consortia for Improving Medicine with Innovation & Technology, Boston)
The Latest on COVID-19 Boosters
Posted on by Dr. Francis Collins
More than 180 million Americans, including more than 80 percent of people over age 65, are fully vaccinated against the SARS-CoV-2 virus responsible for COVID-19. There’s no question that full vaccination is the best way to protect yourself against this devastating virus and reduce your chances of developing severe or long-lasting illness if you do get sick. But, to stay ahead of this terrible virus, important questions do remain. A big one right now is: How soon will booster shots be needed and for whom?
The answers to this question will continue to evolve as more high-quality data become available. But here’s what we know right now for the Pfizer-BioNTech booster. Late last week, Dr. Rochelle Walensky, the Director of the Centers for Disease Control and Prevention (CDC), recommended that:
- Those 65 years and older and residents in long-term care settings should receive a booster shot at least 6 months after being fully vaccinated with the Pfizer-BioNTech vaccine,
- People aged 50–64 years with underlying medical conditions should receive a booster shot at least 6 months after being fully vaccinated with the Pfizer-BioNTech vaccine,
- Individuals aged 18–49 years with underlying medical conditions may receive a booster shot at least 6 months after getting fully vaccinated with their Pfizer-BioNTech vaccine, based on their individual benefits and risks.
- Frontline workers who received the Pfizer-BioNTech vaccine may receive a booster. This group includes anyone age 18 through 64 whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of COVID-19. [1]
Taken together, these CDC recommendations are in line with those issued two days earlier by the Food and Drug Administration (FDA) [2].
Some of the most-compelling data that was under review came from an Israeli study, published recently in the New England Journal of Medicine, that explored the benefit of booster shots for older people [3]. Israel, with a population of around 9 million, has a national health system and one of the world’s highest COVID-19 vaccination rates. That country’s vaccination campaign, based solely on Pfizer-BioNTech, was organized early in 2021, and so its experience is about three months ahead of ours here in the U.S. These features, plus some of the world’s largest integrated health record databases, have made Israel an important source of early data on how the Pfizer-BioNTech mRNA vaccine can be expected to work in the real world over time.
Earlier this year, Israeli public health officials noted evidence for an increased number of breakthrough infections, some of which were severe. So, at the end of July 2021, Israel approved the administration of third doses, or “boosters,” of the Pfizer-BioNTech vaccine for people ages 60 and up who had received their second dose at least five months before.
To find out how well these booster shots worked to bolster immune protection against COVID-19, researchers looked to more than 1.1 million fully vaccinated people who were at least 60 years old. They compared the rate of confirmed COVID-19 infection and severe illness from the end of July to the end of August among people who’d received a booster at least 12 days earlier with those who hadn’t gotten boosters.
Nearly 13,500 older individuals who’d been fully vaccinated before March 2021, got a breakthrough infection during the two months of study. Importantly, the rate of confirmed infection in the group that got boosters was 10 times lower on average than in the group that didn’t get boosters. The data on severe illness looked even better. Of course, there could be other factors at play that weren’t accounted for in the study, but the findings certainly suggest that a third Pfizer shot is safe and effective for older people.
Though the Israeli studies on booster shots are a little ahead of the international pack, we are starting to see results from the research underway in the U.S. Last week, for example, Johnson & Johnson announced new data in support of boosters to improve and extend immune protection in those who received its single-dose COVID-19 vaccine [4]. For people who received the Moderna mRNA vaccine, the company has already submitted its data to the FDA for booster authorization. A decision is expected soon.
As the critical evidence on boosters continues to emerge, the most important way to avoid another winter surge of COVID-19 is to follow all public health recommendations. Most importantly, that includes getting fully vaccinated if you haven’t already, and encouraging others around you to do the same. If you’re currently eligible for a booster shot, they are available at 80,000 locations across the nation, and can help you stay healthy and well for the coming holiday season.
For others eager to do everything possible to protect themselves, their families, and their communities against this terrible virus—but who are not yet eligible for a booster—sit tight for now. The data on booster shots are still coming in for folks like me who were immunized with the Moderna or Johnson & Johnson vaccines. It’s likely that the FDA and CDC will widen their recommendations in the coming weeks.
In the meantime, the Delta variant is still out there and circulating. That makes it critical to maintain vigilance. Wear a mask in indoor spaces, keep a physical distance from others, and remember to wash your hands frequently. We are all really tired of COVID-19, but patience is still required as we learn more about how best to stay ahead of this virus.
References:
[1] CDC statement on ACIP booster recommendations. Centers for Disease Control and Prevention news release. September 24, 2021
[2] FDA authorizes booster dose of Pfizer-BioNTech COVID-19 vaccine for certain populations. Food and Drug Administration news release. September 22, 2021
[3] Protection of BNT162b2 vaccine booster against Covid-19 in Israel. Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, Mizrahi B, Alroy-Preis S, Ash N, Milo R, Huppert A. N Engl J Med. 2021 Sep 15.
[4] Johnson & Johnson announces real-world evidence and Phase 3 data confirming strong and long-lasting protection of single-shot COVID-19 vaccine in the U.S. Johnson & Johnson. September 21, 2021.
Links:
COVID-19 Research (NIH)
Breakthrough Infections in Vaccinated People Less Likely to Cause ‘Long COVID’
Posted on by Dr. Francis Collins
There’s no question that vaccines are making a tremendous difference in protecting individuals and whole communities against infection and severe illness from SARS-CoV-2, the coronavirus that causes COVID-19. And now, there’s yet another reason to get the vaccine: in the event of a breakthrough infection, people who are fully vaccinated also are substantially less likely to develop Long COVID Syndrome, which causes brain fog, muscle pain, fatigue, and a constellation of other debilitating symptoms that can last for months after recovery from an initial infection.
These important findings published in The Lancet Infectious Diseases are the latest from the COVID Symptom Study [1]. This study allows everyday citizens in the United Kingdom to download a smartphone app and self-report data on their infection, symptoms, and vaccination status over a long period of time.
Previously, the study found that 1 in 20 people in the U.K. who got COVID-19 battled Long COVID symptoms for eight weeks or more. But this work was done before vaccines were widely available. What about the risk among those who got COVID-19 for the first time as a breakthrough infection after receiving a double dose of any of the three COVID-19 vaccines (Pfizer, Moderna, AstraZeneca) authorized for use in the U.K.?
To answer that question, Claire Steves, King’s College, London, and colleagues looked to frequent users of the COVID Symptom Study app on their smartphones. In its new work, Steves’ team was interested in analyzing data submitted by folks who’d logged their symptoms, test results, and vaccination status between December 9, 2020, and July 4, 2021. The team found there were more than 1.2 million adults who’d received a first dose of vaccine and nearly 1 million who were fully vaccinated during this period.
The data show that only 0.2 percent of those who were fully vaccinated later tested positive for COVID-19. While accounting for differences in age, sex, and other risk factors, the researchers found that fully vaccinated individuals who developed breakthrough infections were about half (49 percent) as likely as unvaccinated people to report symptoms of Long COVID Syndrome lasting at least four weeks after infection.
The most common symptoms were similar in vaccinated and unvaccinated adults with COVID-19, and included loss of smell, cough, fever, headaches, and fatigue. However, all of these symptoms were milder and less frequently reported among the vaccinated as compared to the unvaccinated.
Vaccinated people who became infected were also more likely than the unvaccinated to be asymptomatic. And, if they did develop symptoms, they were half as likely to report multiple symptoms in the first week of illness. Another vaccination benefit was that people with a breakthrough infection were about a third as likely to report any severe symptoms. They also were more than 70 percent less likely to require hospitalization.
We still have a lot to learn about Long COVID, and, to get the answers, NIH has launched the RECOVER Initiative. The initiative will study tens of thousands of COVID-19 survivors to understand why many individuals don’t recover as quickly as expected, and what might be the cause, prevention, and treatment for Long COVID.
In the meantime, these latest findings offer the encouraging news that help is already here in the form of vaccines, which provide a very effective way to protect against COVID-19 and greatly reduce the odds of Long COVID if you do get sick. So, if you haven’t done so already, make a plan to protect your own health and help end this pandemic by getting yourself fully vaccinated. Vaccines are free and available near to you—just go to vaccines.gov or text your zip code to 438829.
Reference:
[1] Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Antonelli M, Penfold RS, Merino J, Sudre CH, Molteni E, Berry S, Canas LS, Graham MS, Klaser K, Modat M, Murray B, Kerfoot E, Chen L, Deng J, Österdahl MF, Cheetham NJ, Drew DA, Nguyen LH, Pujol JC, Hu C, Selvachandran S, Polidori L, May A, Wolf J, Chan AT, Hammers A, Duncan EL, Spector TD, Ourselin S, Steves CJ. Lancet Infect Dis. 2021 Sep 1:S1473-3099(21)00460-6.
Links:
COVID-19 Research (NIH)
Claire Steves (King’s College London, United Kingdom)
mRNA Vaccines May Pack More Persistent Punch Against COVID-19 Than Thought
Posted on by Dr. Francis Collins
Many people, including me, have experienced a sense of gratitude and relief after receiving the new COVID-19 mRNA vaccines. But all of us are also wondering how long the vaccines will remain protective against SARS-CoV-2, the coronavirus responsible for COVID-19.
Earlier this year, clinical trials of the Moderna and Pfizer-BioNTech vaccines indicated that both immunizations appeared to protect for at least six months. Now, a study in the journal Nature provides some hopeful news that these mRNA vaccines may be protective even longer [1].
In the new study, researchers monitored key immune cells in the lymph nodes of a group of people who received both doses of the Pfizer-BioNTech mRNA vaccine. The work consistently found hallmarks of a strong, persistent immune response against SARS-CoV-2 that could be protective for years to come.
Though more research is needed, the findings add evidence that people who received mRNA COVID-19 vaccines may not need an additional “booster” shot for quite some time, unless SARS-CoV-2 evolves into new forms, or variants, that can evade this vaccine-induced immunity. That’s why it remains so critical that more Americans get vaccinated not only to protect themselves and their loved ones, but to help stop the virus’s spread in their communities and thereby reduce its ability to mutate.
The new study was conducted by an NIH-supported research team led by Jackson Turner, Jane O’Halloran, Rachel Presti, and Ali Ellebedy at Washington University School of Medicine, St. Louis. That work builds upon the group’s previous findings that people who survived COVID-19 had immune cells residing in their bone marrow for at least eight months after the infection that could recognize SARS-CoV-2 [2]. The researchers wanted to see if similar, persistent immunity existed in people who hadn’t come down with COVID-19 but who were immunized with an mRNA vaccine.
To find out, Ellebedy and team recruited 14 healthy adults who were scheduled to receive both doses of the Pfizer-BioNTech vaccine. Three weeks after their first dose of vaccine, the volunteers underwent a lymph node biopsy, primarily from nodes in the armpit. Similar biopsies were repeated at four, five, seven, and 15 weeks after the first vaccine dose.
The lymph nodes are where the human immune system establishes so-called germinal centers, which function as “training camps” that teach immature immune cells to recognize new disease threats and attack them with acquired efficiency. In this case, the “threat” is the spike protein of SARS-COV-2 encoded by the vaccine.
By the 15-week mark, all of the participants sampled continued to have active germinal centers in their lymph nodes. These centers produced an army of cells trained to remember the spike protein, along with other types of cells, including antibody-producing plasmablasts, that were locked and loaded to neutralize this key protein. In fact, Ellebedy noted that even after the study ended at 15 weeks, he and his team continued to find no signs of germinal center activity slowing down in the lymph nodes of the vaccinated volunteers.
Ellebedy said the immune response observed in his team’s study appears so robust and persistent that he thinks that it could last for years. The researcher based his assessment on the fact that germinal center reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades, which gives them the capacity to respond multiple times to the same infectious agent.
This study raises some really important issues for which we still don’t have complete answers: What is the most reliable correlate of immunity from COVID-19 vaccines? Are circulating spike protein antibodies (the easiest to measure) the best indicator? Do we need to know what’s happening in the lymph nodes? What about the T cells that are responsible for cell-mediated immunity?
If you follow the news, you may have seen a bit of a dust-up in the last week on this topic. Pfizer announced the need for a booster shot has become more apparent, based on serum antibodies. Meanwhile, the Food and Drug Administration and Centers for Disease Control and Prevention said such a conclusion would be premature, since vaccine protection looks really good right now, including for the delta variant that has all of us concerned.
We’ve still got a lot more to learn about the immunity generated by the mRNA vaccines. But this study—one of the first in humans to provide direct evidence of germinal center activity after mRNA vaccination—is a good place to continue the discussion.
References:
[1] SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, Lei T, Thapa M, Chen RE, Case JB, Amanat F, Rauseo AM, Haile A, Xie X, Klebert MK, Suessen T, Middleton WD, Shi PY, Krammer F, Teefey SA, Diamond MS, Presti RM, Ellebedy AH. Nature. 2021 Jun 28. [Online ahead of print]
[2] SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, Schmitz AJ, Hansen L, Haile A, Klebert MK, Pusic I, O’Halloran JA, Presti RM, Ellebedy AH. Nature. 2021 May 24. [Online ahead of print]
Links:
COVID-19 Research (NIH)
Ellebedy Lab (Washington University, St. Louis)
NIH Support: National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences
How Immunity Generated from COVID-19 Vaccines Differs from an Infection
Posted on by Dr. Francis Collins
A key issue as we move closer to ending the pandemic is determining more precisely how long people exposed to SARS-CoV-2, the COVID-19 virus, will make neutralizing antibodies against this dangerous coronavirus. Finding the answer is also potentially complicated with new SARS-CoV-2 “variants of concern” appearing around the world that could find ways to evade acquired immunity, increasing the chances of new outbreaks.
Now, a new NIH-supported study shows that the answer to this question will vary based on how an individual’s antibodies against SARS-CoV-2 were generated: over the course of a naturally acquired infection or from a COVID-19 vaccine. The new evidence shows that protective antibodies generated in response to an mRNA vaccine will target a broader range of SARS-CoV-2 variants carrying “single letter” changes in a key portion of their spike protein compared to antibodies acquired from an infection.
These results add to evidence that people with acquired immunity may have differing levels of protection to emerging SARS-CoV-2 variants. More importantly, the data provide further documentation that those who’ve had and recovered from a COVID-19 infection still stand to benefit from getting vaccinated.
These latest findings come from Jesse Bloom, Allison Greaney, and their team at Fred Hutchinson Cancer Research Center, Seattle. In an earlier study, this same team focused on the receptor binding domain (RBD), a key region of the spike protein that studs SARS-CoV-2’s outer surface. This RBD is especially important because the virus uses this part of its spike protein to anchor to another protein called ACE2 on human cells before infecting them. That makes RBD a prime target for both naturally acquired antibodies and those generated by vaccines. Using a method called deep mutational scanning, the Seattle group’s previous study mapped out all possible mutations in the RBD that would change the ability of the virus to bind ACE2 and/or for RBD-directed antibodies to strike their targets.
In their new study, published in the journal Science Translational Medicine, Bloom, Greaney, and colleagues looked again to the thousands of possible RBD variants to understand how antibodies might be expected to hit their targets there [1]. This time, they wanted to explore any differences between RBD-directed antibodies based on how they were acquired.
Again, they turned to deep mutational scanning. First, they created libraries of all 3,800 possible RBD single amino acid mutants and exposed the libraries to samples taken from vaccinated individuals and unvaccinated individuals who’d been previously infected. All vaccinated individuals had received two doses of the Moderna mRNA vaccine. This vaccine works by prompting a person’s cells to produce the spike protein, thereby launching an immune response and the production of antibodies.
By closely examining the results, the researchers uncovered important differences between acquired immunity in people who’d been vaccinated and unvaccinated people who’d been previously infected with SARS-CoV-2. Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.
These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.
It’s not entirely clear why these differences in vaccine- and infection-elicited antibody responses exist. In both cases, RBD-directed antibodies are acquired from the immune system’s recognition and response to viral spike proteins. The Seattle team suggests these differences may arise because the vaccine presents the viral protein in slightly different conformations.
Also, it’s possible that mRNA delivery may change the way antigens are presented to the immune system, leading to differences in the antibodies that get produced. A third difference is that natural infection only exposes the body to the virus in the respiratory tract (unless the illness is very severe), while the vaccine is delivered to muscle, where the immune system may have an even better chance of seeing it and responding vigorously.
Whatever the underlying reasons turn out to be, it’s important to consider that humans are routinely infected and re-infected with other common coronaviruses, which are responsible for the common cold. It’s not at all unusual to catch a cold from seasonal coronaviruses year after year. That’s at least in part because those viruses tend to evolve to escape acquired immunity, much as SARS-CoV-2 is now in the process of doing.
The good news so far is that, unlike the situation for the common cold, we have now developed multiple COVID-19 vaccines. The evidence continues to suggest that acquired immunity from vaccines still offers substantial protection against the new variants now circulating around the globe.
The hope is that acquired immunity from the vaccines will indeed produce long-lasting protection against SARS-CoV-2 and bring an end to the pandemic. These new findings point encouragingly in that direction. They also serve as an important reminder to roll up your sleeve for the vaccine if you haven’t already done so, whether or not you’ve had COVID-19. Our best hope of winning this contest with the virus is to get as many people immunized now as possible. That will save lives, and reduce the likelihood of even more variants appearing that might evade protection from the current vaccines.
Reference:
[1] Antibodies elicited by mRNA-1273 vaccination bind more broadly to the receptor binding domain than do those from SARS-CoV-2 infection. Greaney AJ, Loes AN, Gentles LE, Crawford KHD, Starr TN, Malone KD, Chu HY, Bloom JD. Sci Transl Med. 2021 Jun 8.
Links:
COVID-19 Research (NIH)
Bloom Lab (Fred Hutchinson Cancer Research Center, Seattle)
NIH Support: National Institute of Allergy and Infectious Diseases
Meet an Inspiring Researcher Who Helped Create COVID-19 mRNA Vaccines
Posted on by Dr. Francis Collins
More than 170 million Americans already have received COVID-19 vaccines. As this number continues to grow and expand to younger age groups, I’m filled with overwhelming gratitude for all of the researchers who worked so diligently, over the course of decades, to build the scientific foundation for these life-saving vaccines. One of them is Dr. Kizzmekia Corbett, who played a central role in the fact that, in the span of less than a year, we were able to develop safe and effective mRNA-based vaccines to protect against this devastating infectious disease.
As leader of the immunopathogenesis team at NIH’s Dale and Betty Bumpers Vaccine Research Center in Bethesda, MD, Dr. Corbett was ready, willing, and able when the COVID-19 pandemic emerged to take the critical first steps in developing what would become the Moderna and Pfizer/BioNTech mRNA vaccines. Recently, she accepted a position at Harvard University T.H. Chan School of Public Health, Boston, where she will soon open her own viral immunology lab to help inform future vaccine development for coronaviruses and other respiratory viruses.
While she was preparing for her move to Harvard, I had a chance to speak with Dr. Corbett about her COVID-19 research experience and what it was like to get immunized with the vaccine that she helped to create. Our conversation was part of an NIH Facebook Live event in which we connected virtually from our homes in Maryland. Here is a condensed version of our chat.
Collins: You’ve studied SARS, MERS, and other coronaviruses for many years. Then, in early January 2020, like all of us, you heard that something was going on that sounded worrisome in Wuhan, China. What did you think?
Corbett: Well, the story actually began for me on December 31, 2019. My boss Dr. Barney Graham sent me an email at 6 a.m. that said: “Get ready for 2020.” There had been some news of a respiratory virus outbreak in the Wuhan district of China. I honestly wrote it off as probably a strain of the flu. Then, we got back to NIH after the holidays, and it was determined around January 6 that the virus was for certain a coronavirus. That meant our team would be responding to it.
We sat down and planned to monitor the situation very closely. We knew exactly what to do, based on our past work. We would go into full force to make a vaccine—the one now known as “the Moderna vaccine” —as quickly as possible for testing in a clinical trial. The goal was to make the vaccine in 100 days. And so when the genetic sequence of this new virus came out on January 10, I sprung out of bed and so did everyone on the team. It’s been kind of a whirlwind ever since.
Collins: Tell us a little bit more about that. The sequence got posted on the internet by a Chinese scientist. So you have this sequence, and everyone gathers in NIH’s Vaccine Research Center. Then what happens?
Corbett: The cool thing about this type of technology is you don’t even need the lab to design the vaccine. All you need are the letters, or sequence, that encodes the virus’ genetic material displayed on your computer screen. We could actually do the work from our homes, obviously in close conversation with each other.
This sequence is the virus’s genetic code. Just like humans have families—brothers, sisters, cousins—viruses also have families. So, we could see when looking at the sequence of letters, how similar this particular virus was to viruses that we’ve worked with before in the coronavirus family. It was almost like “A-ha! This is the part of the sequence that represents the protein on the surface of the virus.”
We knew that we could take the sequence of that surface protein and use all of the knowledge that we had from previous years to design a vaccine. And that’s what we did. We took that sequence on our computer screen and said we said this is exactly how we want this vaccine to look. The process was as straightforward as that.
Collins: In other words, you already knew that these coronaviruses have spike proteins on their surface and that’s the thing that’s going to be really useful for making an antibody. You’d already taken this approach in developing a vaccine for MERS, right?
Corbett: Exactly, we’d done that for MERS. Vaccines are basically a way to teach your body how to see a pathogen. Over the years, as vaccinology and technology have progressed, different scientists have figured out that you don’t really need the whole virus as a part of the vaccine. You can just take a small portion of that virus to alert your body.
In this case, taking the spike protein and teaching your immune system how to specifically spot and attack it, you can now protect yourself from COVID-19. So, we used the sequence of that spike protein, with some modifications to make it much better as a vaccine. We then deliver that to you as a message—messenger RNA (mRNA) —to get your muscle cells briefly to make the spike protein. Then, your body sees that spike protein hanging out on your cells and makes a really specific immune response to it. That way the next time your body sees the spike protein, if you ever come into contact with the virus, your immune system is armed and ready to attack.
Collins: Say more about this messenger RNA approach. It’s been so revolutionary and one of the reasons that we got vaccines into people’s arms in just 11 months. Had this approach ever been used before?
Corbett: Yes, messenger RNA technologies have been in development from a basic science perspective for over 15 years. A lot of that work was funded by NIH. Soon after I got to NIH, I attended a meeting in London called Transforming Vaccinology. At the time, Moderna was a smaller company that was working to make messenger RNA technologies, mostly centered around cancer therapies. But they had started to test some flu vaccines that used messenger RNA. My question to the presenter was: “Every single time I see you guys present, it looks like mRNA technology has always worked. Can you tell me a time that it hasn’t?” And he said, “I can’t.”
So, our understanding of how this technology works to make really good vaccines predates this pandemic. I think one of the worries that many people have is how fast and how new this technology is. But all science is compounded knowledge—everything builds on itself.
Collins: Right! We only learned about messenger RNA, because back in the 1950s and 1960s, some researchers decided to figure out how the information in our genetic instruction book, our DNA, can ultimately turn into proteins. It turned out that the message that carries that information is made of RNA.
So, you knew which kinds of letters to program into the messenger RNA vaccine. Would you explain how this vaccine, its messenger RNA, produces a spike protein. Where does that step happen?
Corbett: Your cells are machines built for this kind of thing. I like to remind people that, on a day-in, day-out basis, our cells make proteins—all of the hormones and other things our bodies needs to survive. So, we’re not teaching the cells to do anything different than they would normally do. That’s important to understand.
The way that cells do this is by reading the mRNA sequence. As they’re reading that sequence, they chew it up, like eating it, and say, “Okay, this sequence is for this very specific protein.” Then, they make that protein and push it to the surface of your cells. That’s how it happens.
Collins: And for mRNA vaccines, that’s the point when your immune system says “Wait a minute! I don’t recognize that as part of me, so I’ve got to make an antibody to it.” Then you’re off to the races and develop your immunity. Now that this mRNA vaccine strategy has succeeded for COVID-19, could it be applied to other infectious diseases or even non-infectious conditions?
Corbett: Yes, I heard that about 60 new companies have sprouted up in the last year around messenger RNA technology. They have ideas for different types of infectious disease vaccines and cancer therapies. I expect that this technology will be transformative to medicine in general.
Collins: Here’s a question from social media: “Why does it take two shots for the Pfizer and the Moderna mRNA vaccines? Why isn’t one good enough?”
Corbett: The way that these vaccines work is much like an alarm clock. Imagine your immune system is in bed and the first shot is the alarm clock going off to say, “Hey, wake up and get ready.” And just like I did this morning, the immune system pressed snooze and took a little nap. But when you hear the alarm clock the second time, it’s like someone rushing into your room and pouring a cold bucket of water on you. You have no choice but to get out of bed.
That’s what the second dose of the vaccine does. It pushes your immune response to the next level. That’s why you need two shots to get the type of efficacy that you want and be fully protected for the optimal immune response.
Collins: You were a co-leader of the team that created what became the Moderna vaccine—and you ended up getting immunized with the Moderna vaccine. What did that feel like?
Corbett: It was pretty surreal. I cried. At the end of it, I felt a lot of relief after getting my vaccine, particularly after getting the second dose. There was this breath of fresh air. It was also a birthday present. I got my second dose the day before my 35th birthday, as a birthday present to myself.
Collins: I have to admit, I cried a little bit too after my second dose. It’s just the sense of relief and incredible gratitude that we’ve reached this point. Here we are with vaccines that have 95 percent effectiveness and an incredibly good safety record, which is almost better than we could have hoped for. I’m a person of faith, so there were a lot of my prayers that went into this and it sure felt like they got answered.
Corbett: Yes, same.
Collins: You are out there a lot talking to people about the vaccines. There are still about 100 million Americans that have not yet received their first dose. Many of them still unsure about getting vaccinated. What do you say to those who are on the fence?
Corbett: In this past year, I’ve spent a lot of time talking about the vaccine with people in the community. One thing that I realized, is that I don’t need to say anything unless I’m asked. I think it’s important that I listen first, instead of just speaking.
So I do that, and I try to answer people’s inquiries as specifically as possible. But people have some very broad questions. One thing that is happening is people are seeing vaccines being developed right before their eyes. That can be a little confusing. I try to explain the process, how we went from the preclinical stage all the way to the point of getting the vaccine to hundreds of millions of people. I explain how each step along the way is very highly vetted by regulatory agencies and data safety monitoring committees. I also tell them that the monitoring continues. People from the clinical trials are still being evaluated, and there’s monitoring in the real world as the vaccine is being rolled out. I think that all of those things are really important for people to know.
Collins: Another question from social media: “As a successful scientist, what advice would you give to people who are thinking about a career in science?”
Corbett: If you think you’re interested, you just have to start. There are internship programs, there are scholarship programs, there are shadowing programs all over this country and even globally that can help you get your feet wet. I think the first thing that you want to do with any career is to figure out whether or not you like it. The only way that you can do that is to just explore, explore, explore.
Collins: Didn’t you kind of roll up your sleeves and take the plunge at a young age?
Corbett: Yes, at age 16, I went off and did summer internships at the University of North Carolina. I was able to see first-hand the day-to-day life of science and what being a scientist would look like. That was really important for me. That’s what I mean by exploring.
Collins: And a follow-up question: “Is the biomedical research community welcoming to women of color?”
Corbett: Not always, frankly. I was very fortunate to have been under the wings of a lot of mentors and advocates, who have helped to advance my career to where it is now. I had great mentors at NIH. My graduate school mentor was amazing, and my main collaborator in the coronavirus field was on my dissertation committee. Even prior to this pandemic, when I was doing work that was very obscure, he checked on me very often and made sure that he had a sense of where I wanted to go and how he could help me get there, including collaborating with me.
That kind of thing is very important, particularly for women of color or anyone from a marginalized community. That’s because there will be a point where there might be a glass ceiling. Unfortunately, we don’t necessarily have the tools to break those just yet. So, someone else is going to have to break those down, and most often than not, that person is going to have to be a white man. Finding those people who are allies with you and joining in your fight for your career trajectory is very helpful.
I remember when I was choosing a college, it was a very difficult decision for me. I got accepted into Ivy League schools, and I’d gone to all of the scholarship weekends all over the country. When I was making the decision, my dad said, “Kizzy, just always go where there is love.”
That really sticks to me with every single choice that I make around my career. You want to be at a place that’s welcoming, a place that understands you, and a place that fosters the next version of who you are destined to be. You need to make sure to step back outside of the day-to-day stuff and say, “Okay, does this place love me and people like me?” It’s important to remember that’s how you thrive: when you are comfortable in and in love with your environment.
Collins: Yes, we have to move our scientific workforce into a place where it is not necessary for a white man to advocate for a talented Black woman. There’s something very wrong with that particular circumstance. As NIH Director, I want to assure you, we are motivated more than ever to change that, including through a new initiative called UNITE. We’re missing out on welcoming the talents of so many folks who currently don’t see our research agenda as theirs, and we need to change that.
Kizzmekia, this has been a lot of fun. Thank you for giving us a half-hour of your time when you’re in the midst of this crazy two-week period of moving from Bethesda to Boston. We wish you the very best for this next chapter, which I know is going to be just amazing.
Corbett: Thank you so much.
Links:
Video: COVID-19 mRNA Vaccine Q & A – Kizzmekia Corbett and Francis Collins (NIH)
Video: Lead COVID-19 scientist Kizzmekia Corbett to join Harvard Chan School faculty (Harvard University, Boston)
COVID-19 Research (NIH)
Dale and Betty Bumpers Vaccine Research Center (National Institute of Allergy and Infectious Diseases/NIH)
UNITE Initiative (NIH)
Studies Confirm COVID-19 mRNA Vaccines Safe, Effective for Pregnant Women
Posted on by Dr. Francis Collins
Clinical trials have shown that COVID-19 vaccines are remarkably effective in protecting those age 12 and up against infection by the coronavirus SARS-CoV-2. The expectation was that they would work just as well to protect pregnant women. But because pregnant women were excluded from the initial clinical trials, hard data on their safety and efficacy in this important group has been limited.
So, I’m pleased to report results from two new studies showing that the two COVID-19 mRNA vaccines now available in the United States appear to be completely safe for pregnant women. The women had good responses to the vaccines, producing needed levels of neutralizing antibodies and immune cells known as memory T cells, which may offer more lasting protection. The research also indicates that the vaccines might offer protection to infants born to vaccinated mothers.
In one study, published in JAMA [1], an NIH-supported team led by Dan Barouch, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, wanted to learn whether vaccines would protect mother and baby. To find out, they enrolled 103 women, aged 18 to 45, who chose to get either the Pfizer/BioNTech or Moderna mRNA vaccines from December 2020 through March 2021.
The sample included 30 pregnant women,16 women who were breastfeeding, and 57 women who were neither pregnant nor breastfeeding. Pregnant women in the study got their first dose of vaccine during any trimester, although most got their shots in the second or third trimester. Overall, the vaccine was well tolerated, although some women in each group developed a transient fever after the second vaccine dose, a common side effect in all groups that have been studied.
After vaccination, women in all groups produced antibodies against SARS-CoV-2. Importantly, those antibodies neutralized SARS-CoV-2 variants of concern. The researchers also found those antibodies in infant cord blood and breast milk, suggesting that they were passed on to afford some protection to infants early in life.
The other NIH-supported study, published in the journal Obstetrics & Gynecology, was conducted by a team led by Jeffery Goldstein, Northwestern’s Feinberg School of Medicine, Chicago [2]. To explore any possible safety concerns for pregnant women, the team took a first look for any negative effects of vaccination on the placenta, the vital organ that sustains the fetus during gestation.
The researchers detected no signs that the vaccines led to any unexpected damage to the placenta in this study, which included 84 women who received COVID-19 mRNA vaccines during pregnancy, most in the third trimester. As in the other study, the team found that vaccinated pregnant women showed a robust response to the vaccine, producing needed levels of neutralizing antibodies.
Overall, both studies show that COVID-19 mRNA vaccines are safe and effective in pregnancy, with the potential to benefit both mother and baby. Pregnant women also are more likely than women who aren’t pregnant to become severely ill should they become infected with this devastating coronavirus [3]. While pregnant women are urged to consult with their obstetrician about vaccination, growing evidence suggests that the best way for women during pregnancy or while breastfeeding to protect themselves and their families against COVID-19 is to roll up their sleeves and get either one of the mRNA vaccines now authorized for emergency use.
References:
[1] Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women. Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, Chandrashekar A, Patel S, Apraku Bondzie E, Sellers D, Barrett J, Sanborn O, Wan H, Chang A, Anioke T, Nkolola J, Bradshaw C, Jacob-Dolan C, Feldman J, Gebre M, Borducchi EN, Liu J, Schmidt AG, Suscovich T, Linde C, Alter G, Hacker MR, Barouch DH. JAMA. 2021 May 13.
[2] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in pregnancy: Measures of immunity and placental histopathology. Shanes ED, Otero S, Mithal LB, Mupanomunda CA, Miller ES, Goldstein JA. Obstet Gynecol. 2021 May 11.
[3] COVID-19 vaccines while pregnant or breastfeeding. Centers for Disease Control and Prevention.
Links:
COVID-19 Research (NIH)
Barouch Laboratory (Beth Israel Deaconess Medical Center and Harvard Medical School, Boston)
Jeffery Goldstein (Northwestern University Feinberg School of Medicine, Chicago)
NIH Support: National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institute of Child Health and Human Development; National Center for Advancing Translational Sciences; National Institute of Biomedical Imaging and Bioengineering
