Scientists at the U.S. Food and Drug Administration (FDA) have modified a standard laboratory test so that it can evaluate two types of inactivated (killed) poliovirus vaccines (IPV): the conventional one (cIPV) made from wild highly virulent polioviruses and the new one made from safer attenuated Sabin strains (sIPV).

The ability of the FDA test to measure the potency of both cIPV and sIPV is important because it could help meet the increased demand for more IPV that is gradually replacing the use of oral poliovirus vaccine (OPV) worldwide. OPV is trivalent, that is, it is made using polioviruses Types 1, 2, and 3. The trivalent formulation was widely used in countries with limited resources because it is inexpensive and is administered by placing two drops into the mouth of a child, not requiring skilled personnel to do it. However, people who receive OPV may shed the virus and can infect others, especially those who are not vaccinated. In areas with low vaccination rates, the OPV virus can continue to infect new individuals. In rare cases, the OPV virus can accumulate changes over time and become like wild poliovirus (WPV). These new viruses are called vaccine-derived polioviruses (VDPV) and can cause polio disease.

After eradication of wild type 2 polioviruses in 2015 and to prevent the emergence of Type 2 VDPVs, the trivalent OPV was replaced by an OPV that contained only two polioviruses, Types 1 and 3. In order to continue to provide protection against Type 2 poliovirus, the World Health Organization (WHO) directed that OPV administration be supplemented with an IPV that contained Type 2, as well as Types 1 and 3. This additional need for IPV significantly increased the global demand for IPV.

In addition, using the wild strains to make cIPV requires expensive biosafety and biosecurity measures to be taken to prevent accidental release of the virus into the environment, complicating its introduction in resource-limited countries. Therefore, WHO encouraged new manufacturers in developing countries to manufacture IPV from attenuated Sabin strains rather than the wild strains. However, some of the tests used to assess the potency and stability of cIPV are not suitable for assessing sIPV because of the differences between the wild and attenuated of viruses. 

Since the FDA assay works well with both types of vaccine, it could facilitate and speed the development of additional sIPV by assessing vaccine quality and stability by providing accurate results regardless of which type of IPV is being tested.

Unlike previous versions of this type of this test, called an enzyme-linked immunosorbent assay (ELISA) that relied on mouse antibodies, the FDA assay uses human antibodies that better recognize protective antigens of the virus. They were prepared by cloning human lymphocytes and selecting monoclonal antibodies specific to protective D-antigens of each serotype of the virus. They were used to immobilize on the surface the vaccine antigen from either cIPV or sIPV. Another monoclonal antibody that recognizes and binds to all three serotypes of poliovirus was used to detect and quantify the captured protective antigen. The human monoclonal antibodies used in this assay were previously isolated by FDA scientists in collaboration with their colleagues at Lankenau Institute for Medical Research in Philadelphia, PA.

The FDA ELISA offers vaccine manufacturers and national control laboratories responsible for quality control of cIPV and sIPV a sustainable supply of the same monoclonal antibodies, which could standardize the testing in all laboratories worldwide and eliminate the need for them to develop and validate their own reagents.

Title

Universal ELISA for quantification of D-antigen in inactivated poliovirus vaccines

Journal of Virological Methods 276 (2020) 113785
https://doi.org/10.1016/j.jviromet.2019.113785

Authors

Diana Kouiavskaia^a, Rama Devudu Puligedda^b, Scott K. Dessain^b, Konstantin Chumakov^a,c,*

^a FDA Center for Biologics Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States
^b Lankenau Institute for Medical Research, 100 Lancaster Ave, Wynnewood, PA 19096, United States
^c Global Virus Network Center of Excellence, 725 West Lombard St, Baltimore, MD 21201, United States