Vaccination against SARS-CoV-2, the virus that causes COVID-19, has offered effective protection in both adults and children. Even when Delta became the dominant variant in the U.S., CDC data from April to July 2021 showed that those vaccinated had a five-fold reduction in risk of infection, more than 10-fold reduction in risk of hospitalization, and more than 10 times reduced risk of death compared with people who remained unvaccinated. Furthermore, a COVID-19 vaccine has been reported to be 100% effective in children ages 12 to 15 years after a two-dose course. Nonetheless, the pandemic continues to have a devastating impact in the U.S. and worldwide. The total COVID-19 case count was upwards of 47.5 million in the U.S. and total deaths were over 5.15 million worldwide as of November 19, 2021. The emergence of more transmissible variants (i.e., Delta and Omicron) and persistent vaccine hesitancy has hindered herd immunity, allowing the virus to continue plaguing the world.

Despite the effectiveness of available vaccines, there is scientific evidence of waning immunity in some fully vaccinated populations and breakthrough infections are on the rise, due in part to the Delta variant. The heavily mutated Omicron variant appears to be even more contagious, and it may evade antibodies produced by previous infection or vaccination. 

Vaccine uptake in the U.S. is not universally enthusiastic. The general public’s confidence in the COVID-19 vaccines appears shaky, with about one-third of people saying they believe the vaccines are not working as well as promised. The top reasons cited for why people remain unvaccinated are newness of the currently available COVID-19 vaccines and worries about side effects. Others have an inherent mistrust of the healthcare system that stokes vaccine hesitancy and skepticism among specific populations (e.g., African Americans). This hesitancy is not only impacting adults, but children as well. 

The Food and Drug Administration (FDA) recently authorized a COVID-19 vaccine for the nation’s 28 million children ages 5 to 11 years, which could lower the COVID-19 toll if new, more transmissible coronavirus variants were to emerge. However, uptake of COVID-19 vaccinations in children has been slow, and, as of December 2021, only ~17% of 5- to 11-year-olds have received at least one dose, and a third of parents surveyed said in a poll earlier this year that they would take a “wait and see” approach before getting their children vaccinated.

Being vaccinated is not a new concept for many Americans, as many adults have received immunizations since childhood and have had their children receive standard immunizations. Even so, many Americans still express a desire for more vaccine options when it comes to COVID-19. In a Harris Poll survey conducted in July 2021 in which 65% of Americans surveyed believed they should have more COVID-19 vaccine options to choose from, 40% of parents surveyed whose children were not yet vaccinated for COVID-19 said they would be more likely to get their child vaccinated for COVID-19 if there was an option that was more effective against Delta and future variants. So maybe there is room in the national arsenal for additional vaccines. As immunization is standard for most of the nation, perhaps vaccines that utilize a more familiar technology, such as the one that ended the polio epidemic in the U.S., could provide an additional choice for Americans.

Inactivated whole virus vaccines, such as the polio vaccine, may have an advantage against mutating viruses: they contain all the same protein antigens as the live virus but without the risk of causing disease. Unlike mRNA and viral vectored COVID-19 vaccines, which target the external spike protein of SARS-CoV-2 — the portion of the virus where many of the mutations are occurring — inactivated whole virus vaccines are designed to build immunity to external and internal protein targets of the virus. This broad antigenic recognition could theoretically confer additional protection under circumstances in which the virus is rapidly mutating, but more data are necessary. Importantly, inactivated whole virus vaccines have been traditionally used as the platform of choice for multiple childhood and adult vaccines given their relatively benign side effect profile.

Several developers, such as Sinovac, Sinopharm, Valneva, Bharat Biotech and its partner Ocugen, are all investigating inactivated whole virus vaccines for COVID-19. In the U.S., Ocugen has obtained the rights to an inactivated whole virus COVID-19 vaccine from Bharat Biotech and filed for emergency use authorization for pediatric use. Ocugen’s filing is based on a study demonstrating the effectiveness and safety of its candidate vaccine in 525 children in India. So far, more than 100 million doses of this vaccine have been administered to adults in 17 countries outside the U.S. The World Health Organization has also recently granted Bharat Biotech’s COVID-19 vaccine an emergency use listing for use in adults aged 18 years and older in addition to the COVID-19 vaccines from Sinovac and Sinopharm. It should be noted that even within the inactivated whole virus class of vaccines, there are important differences in makeup. For instance, Bharat Biotech/Ocugen and Valneva both employ adjuvant boosters known as toll-like receptor agonists (TLRs), which are intended to induce a robust immune memory response. While it is unclear if Sinovac and Sinopharm plan on submitting their COVID-19 vaccines for emergency use authorization in the U.S., Ocugen is intending to develop and manufacture its inactivated whole virus candidate in the U.S. 

Looking at the future vaccine landscape, several additional COVID-19 vaccines have been approved in other countries and many vaccines are still in development. Only 42.7% of the population has been fully vaccinated worldwide and the pandemic is not over yet. The vaccine arsenal is not even close to full. There is a need to continue to expand the vaccine arsenal as the world continues to face emerging viral variants, waning immunity, limited or no access to COVID-19 vaccines in some parts of the world, vaccine hesitancy and a lack of interest in personal prevention against COVID-19 in some individuals. The fact of the matter is, as long as the COVID-19 vaccination rate remains suboptimal, and variants continue to emerge, the virus will win.


This article was written by Real Chemistry, in partnership with Ocugen, Inc.