In the United States, we have three vaccines approved or under emergency use authorization for COVID-19: the vaccines known as Moderna (mRNA-1273), Pfizer (BNT162b2), and Johnson & Johnson (Ad26COVS1). However, there are eight COVID-19 vaccines that have gained emergency use listing from the World Health Organization (WHO) at this point in the pandemic, and two are likely to be approved in the US soon, so I wanted to go over the details of these two vaccines.
For one thing, do we need additional vaccines? I think we do, for two reasons. One is that there is still a segment of the US population that is hesitant to take the mRNA or DNA vaccines. In fact, the US (with a 67% full vaccination rate) has lower rates of COVID-19 vaccination than many Latin American and European countries. The mRNA and DNA vaccine technologies use genetic material coding for part of the spike protein of SARS-CoV-2. After receiving the vaccine, the human host translates that genetic material into the spike protein and raises an immune response to the protein, and the genetic material and spike protein both degrade, leaving behind a powerful immune arsenal of T cells, B cells, and antibodies. Because of misinformation in the US on these vaccines, alternative vaccines that use more "traditional" designs than mRNA or DNA technology may boost our vaccine uptake.
The second reason is the emergence of variants of concern in SARS-CoV-2 that include many mutations across the spike protein. With the variants, boosters that show the host a wider piece of the spike protein or the entire virus may be useful to generate a broader immune response against variants.
The Novavax (NVX-CoV2373) vaccine will be reviewed by the US Food and Drug Administration (FDA) Vaccines and Available Biological Products Advisory Committee on June 7, 2022, and is expected to gain emergency use authorization status. NVX-CoV2373 contains a recombinant SARS-CoV-2 nanoparticle vaccine, constructed from the full-length wild-type SARS-CoV-2 spike protein, including the piece of the protein that binds directly to the host cell — the receptor binding domain (RBD). The RBD tends to be more conserved (stable) across the variants. The Novavax vaccine comes co-formulated with a Matrix-M1 adjuvant, which is an ingredient added to the vaccine to generate a stronger immune response. In the early-phase trials of the Novavax vaccine, strong T-cell (CD4 and CD8) and antibody responses were raised in response to the vaccine.
Novavax is a more traditional vaccine — a protein subunit vaccine similar to those used to protect against influenza, pertussis (whooping cough), diphtheria, and tetanus. A more traditional vaccine could overcome hesitancy in some of our populations in the US. In the first phase 3 trial of Novavax published in The New England Journal of Medicine, two doses of the vaccine were 89.7% protective against symptomatic infection and 100% protective against severe disease. In a later phase 3 study in the time when the Alpha variant was circulating conducted in the US and Mexico, the vaccine was 90.4% effective against symptomatic infection and 100% protective against severe disease. Although more study in the Delta and Omicron variant eras is needed, Novavax was approved by the WHO, has been approved in the UK, Europe, and Canada and is likely to be authorized in the US after this week
The Covaxin vaccine may be the next vaccine approved in the United States if all goes well with a current trial. There are currently three vaccines on the WHO list that are inactivated whole virus vaccines combined with different adjuvants: Sinopharm and Sinovac (both made in China) and Covaxin. Covaxin was originally developed in India by a company named Bharat Pharmaceuticals but now has a US manufacturer named Ocugen. Of these three, Covaxin seems to be the most capable of creating a strong immune response with just two doses, since the WHO recommends a third shot in populations receiving Sinopharm and Sinovac. Covaxin's advantage over the two Chinese-made vaccines is probably due to a more powerful adjuvant used in the compound, an adjuvant developed with funding by the US National Institutes of Health.
Because Covaxin shows the immune system the entire virus in an inactivated form, the vaccine elicits a broad immunologic response against not only the spike protein but also the RBD, the nucleocapsid protein of SARS-CoV-2, and other parts of the virus. The vaccine also elicits strong cellular immune responses, which is vital for long-term protection from the vaccine. Because these immune responses are so broad, they are active against all known variants.
The original phase 3 study of this vaccine showed a high protective efficacy against SARS-COV-2, with the protection against severe disease being 93.4%. Healthcare workers in India who received Covaxin well into the Delta variant era continued to be highly protected. While the two mRNA vaccines we have in the US showed reduced vaccine effectiveness against Omicron (for mild disease) because the Omicron BA1 variant has 32 mutations across its spike protein that distinguish it from the ancestral strain, immune responses from the Covaxin vaccine continued to neutralize the Omicron variant.
Another major advantage of Covaxin is that it has been tested in a younger cohort of participants 2-18 years of age. A phase 2/3, open-label, multicenter study was conducted in India from May to July 2021, to evaluate the safety, reactogenicity, and immunogenicity of the vaccine in this group and found excellent immune responses across the entire cohort.
Moreover, among the 526 participants in the pediatric clinical trial, no serious adverse effects, including myocarditis or pericarditis, were reported. Safety evaluations in adults after the administration of millions of doses have similarly found no major adverse effects. Given that our rate of two-dose vaccination in the United States among children aged 5-11 is still only 39%, the approval of an alternative vaccine formulation for younger children in the United States may boost uptake.
As we continue to manage SARS-COV-2 into the future, because the virus does not have properties that portend its eradication (eg, it has animal reservoirs), a booster that shows us the whole virus may be helpful for managing variants. In fact, data have shown that a Covaxin booster after receiving other vaccines neutralizes the Delta and Omicron variants. Ocugen's original application for the 2- to 18-year-old age group was denied by the FDA on March 4, 2022, because the vaccine has mainly been administered in India and not in US populations. Therefore, Ocugen launched a phase 2/3 trial in the US among 400 adults in February, which is currently recruiting. If Covaxin is safe and boosts antibodies in this US-based population, the vaccine should be authorized later this year.
On a personal note, I am going to India in July and plan to get a Covaxin vaccine to boost my three-dose mRNA vaccine series, which will hopefully be a strategy widely available to all Americans later this year or next.
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Cite this: Monica Gandhi. Novavax and Covaxin: What You Need to Know - Medscape - Jun 06, 2022.