Scientists at the U.S. Food and Drug Administration (FDA) showed that if an effective vaccine were available, its use in drug user populations has the potential to reduce hepatitis C virus (HCV) transmission and reduce new hepatitis C infections in this population, even if the virus replicates at low levels in the vaccinated users.

The FDA study is important because HCV can cause liver disease that can be fatal, and the major cause of HCV transmission in the U.S. is injection drug use, by sharing needles or syringes. Moreover, vaccines under development have not been able to completely block infection following exposure to the virus. Development of effectives vaccines for hepatitis C has been difficult for a variety of reasons, including challenges with developing a relevant animal model, viral diversity and determining the immune responses that correlate with immunity and protection.

Specifically, the study showed that reducing the amount of virus remaining in the dead space of the needle used to inject drugs could reduce the risk of HCV transmission from an infected to an uninfected user. Dead space is the area where blood from the infected user can remain after the rest of the blood is expelled from the needle. (Drug users draw up blood into the needle to verify that it is inside a vein, then push it back out of the needle.) When another person shares the syringe and needle, blood in the dead space is transferred to that individual.

The FDA scientists suggest that a vaccine that significantly reduced the amount of HCV in an injecting drug user could result in such a small amount of virus remaining in the dead space of the needle that the subsequent temporary, low-level replication of virus would significantly reduce the risk of that individual transmitting the virus to anyone sharing a syringe. This reduction in risk of transmission could contribute to the overall effectiveness of a vaccine program among injecting drug users. Such a vaccine might also overcome barriers to the successful treatment of injecting drug users with anti-HCV drugs, such as cost, difficulties in identifying infected individuals, and risk of reinfection.

The FDA scientists based their study on a mathematical model they developed to determine the probability of HCV transmission from an infected to an uninfected individual who shared a syringe and needle.

The scientists calculated that the risk of HCV transmission from sharing syringes increased about 10 times as the amount of virus in the syringe increased 25 times. However, for individuals with pre-existing immunity that rapidly controlled HCV, the risk decreased to 1-25% depending on HCV titer and syringe type. Thus, the FDA model suggests that HCV vaccination could reduce transmission among people sharing syringes, even if there is a brief period of viral replication following exposure to the virus during injection drug use.

The findings of the FDA study could be used to support development of comprehensive modeling approaches aimed at understanding how reduced HCV levels, reduced periods of infection, and multiple syringe sharing can impact the spread and long-term prevalence of HCV.

TITLE

Modeling of patient virus titers suggests that availability of a hepatitis C vaccine could reduce HCV transmission among injecting drug users

Science Translational Medicine

AUTHORS

Marian Major¹*, Alexander Gutfraind^2,3#, Louis Shekhtman^2,4#, Qingwen Cui¹, Alla Kachko¹, Scott J Cotler², Behzad Hajarizadeh⁵, Rachel Sacks-Davis^6,7, Kimberly Page⁸, Basmattee Boodram³, and Harel Dahari²*

¹Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 20993 USA;
²The Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Chicago, Maywood, IL, 60153 USA;
³Epidemiology & Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, 60612 USA;
⁴Department of Physics, Bar-Ilan University, Ramat Gan, 52990 Israel
⁵The Kirby Institute, UNSW Australia, Sydney, 2052 Australia
⁶Disease Elimination Program, Burnet Institute, Melbourne, 3004 Australia
⁷Department of Medicine, University of Melbourne, Parkville, 3010 Australia
⁸Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 USA

*To whom correspondence should be addressed: [email protected] or [email protected]