Viruses have triggered numerous outbreaks across the globe, prompting the development of various rapid response measures. Among these are inactivated vaccines, including killed viruses, mRNA-based vaccines, and subunit vaccines. While these approaches have proven effective in reducing the severity of diseases, they often fall short in preventing the spread of the virus, as demonstrated during the SARS-CoV-2 pandemic. In light of these limitations, our efforts are focused on advancing the development of live attenuated vaccines, which hold greater potential for curbing virus transmission.
Leveraging our understanding of virus replication and evolution, we have developed innovative poliovirus vaccine strains aimed at eradicating global poliomyelitis. While live-attenuated polio vaccines, such as the Sabin strains, have significantly reduced polio cases over the past few decades, vaccine-derived polioviruses (VDPVs) remain a major obstacle to complete eradication. To address this challenge, we analyzed poliovirus evolution to create genetically stable, safer, and more immunogenic novel oral polio vaccines (nOPVs) for all three poliovirus types. These advancements represent a critical step toward overcoming the final barriers to a polio-free world (Konopka-Anstadt et al., 2020; Stern et al., 2017; Yeh et al., 2023, 2020). Among them, nOPV1 and nOPV3 are being tested in phase 2 clinical trials. nOPV2 has been granted WHO pre-qualification and over 1 billion doses have been administered in over 35 countries since March 2021. Using lessons learned from nOPVs, we target other enteroviruses to generate promising vaccine strains with manipulated tissue tropism.

Related Publications

Konopka-Anstadt, J.L., Campagnoli, R., Vincent, A., Shaw, J., Wei, L., Wynn, N.T., Smithee, S.E., Bujaki, E., Yeh, M.T., Laassri, M., Zagorodnyaya, T., Weiner, A.J., Chumakov, K., Andino, R., Macadam, A., Kew, O., Burns, C.C., 2020. Development of a new oral poliovirus vaccine for the eradication end game using codon deoptimization. npj Vaccines 5, 26. https://doi.org/10.1038/s41541-020-0176-7

Yeh, M.T., Bujaki, E., Dolan, P.T., Smith, M., Wahid, R., Konz, J., Weiner, A.J., Bandyopadhyay, A.S., Damme, P.V., Coster, I.D., Revets, H., Macadam, A., Andino, R., 2020. Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence. Cell Host Microbe 27, 736-751.e8. https://doi.org/10.1016/j.chom.2020.04.003

Yeh, M.T., Smith, M., Carlyle, S., Konopka-Anstadt, J.L., Burns, C.C., Konz, J., Andino, R., Macadam, A., 2023. Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3. Nature 619, 135–142. https://doi.org/10.1038/s41586-023-06212-3

Stern, A., Yeh, M.T., Zinger, T., Smith, M., Wright, C., Ling, G., Nielsen, R., Macadam, A., Andino, R., 2017. The Evolutionary Pathway to Virulence of an RNA Virus. Cell 169, 35-46.e19. https://doi.org/10.1016/j.cell.2017.03.013