Covid-19 (SARS-CoV-2) Vaccines: Novavax NVX‑CoV2373/SII Covovax

Covid-19 (SARS-CoV-2) Vaccines: Novavax NVX‑CoV2373/SII Covovax

Most vaccines against the Covid-19 (SARS-CoV-2) virus target its spike protein. This protein enables the virus to invade the cell, and is an essential component.

The NVX‑CoV2373 vaccine (being manufactured by Serum Institute of India as Covovax) uses five micrograms (mcg) of recombinant spike protein as nanoparticles in injectable form, together with the Matrix-M1 adjuvant. This recombinant nanoparticle vaccine is created by introducing a spike protein gene into a baculovirus and growing the virus in moth cell cultures. The spike protein chains are extracted, purified, and formulated with the adjuvant Matrix-M1.

Vaccine Technologies

Vector vaccines: Oxford/AstraZeneca vaccine, the Sputnik-V vaccine, the Johnson and Johnson vaccine, a vaccine from CanSino Biological Inc/Beijing Institute of Biotechnology, and a vaccine from Janssen Pharmaceutical Companies.

Whole-cell inactivated vaccines: Covaxin, SinoVac, and Sinopharm.

mRNA-based vaccines: BioNTech/Pfizer vaccine, Moderna/National Institute of Allergy and Infectious Diseases vaccine.

Adjuvanted recombinant protein nanoparticle vaccine: Novovax NVX-CoV2373.

Efficacy- Phase 1 and 2 Studies

The vaccine has been tried in adult volunteers in a two-dose schedule, 21 days apart.

It is effective, generating strong, antigen-specific CD4+ T-cell responses. The antibody response was also potent; neutralizing antibody levels after two doses were about four times those seen in people recovering from moderate to severe Covid-19.

These studies used two doses: 5 mcg and 25 mcg. Since even a single dose of 5 mcg generated a robust antibody response, phase 3 studies used only the 5 mcg dose.

Efficacy- Phase 3 studies

One efficacy study in UK with over 15,000 participants showed 95.6% efficacy against infection by the original strain, and 100% against severe disease. However, the efficacy against the Alpha variant (B.1.1.7 or UK variant) was 86%.

A large study carried out in USA and Mexico recruited 29,960 people for a phase 3 study. NVX-CoV2373 has an efficacy of 90.4% against Covid-19 disease, and 100% protection against moderate or severe disease.

The NVX-CoV2373 vaccine is effective in elderly people, and in those with comorbidities (cardiac and pulmonary conditions, and people with HIV on anti-retroviral treatment).

Tested in the elderly, people with heart and lung disease, and people with HIV

Efficacy Among High-Risk People

Earlier vaccine studies have left out groups of people that are at particularly high risk for Covid-19 infection and for severe disease. The NVX-CoV2373 trial included several of them:

  • People over 65 years of age.
  • People with frequent occupational exposure to Covid-19.
  • People with comorbidities.

Among this population, the efficacy of the vaccine was 91%.


A dose of the vaccine contains 5 mcg of the recombinant spike protein nanoparticles, adjuvanted with 50 mcg Matrix-M.
Two doses are given intramuscularly into the upper arm, 21 days apart.

Safety and Adverse Events

Most local and systemic reactions are mild, and do not last more than two days after the injection. The most common local adverse effect is injection site pain.

Rare adverse events are headache, fatigue, and malaise. A few recipients report fever, joint pain, and tenderness.

There were no events after the first dose that required withholding the second dose. The researchers found no heart problems or blood clots. No severe side effects were reported.

No serious or fatal adverse events reported

Activity Against Covid-19 (SARS-CoV-2) Variants

The Beta variant, also known as B.1.351, was first identified in South Africa. Like the other variants of concern, it demonstrates changes in the spike protein target areas that may render the vaccine-generated antibodies ineffectual.

A study in South Africa was carried out when the predominant strain was B.1351, the Beta variant. Among people without HIV, the vaccine efficacy was 60% against Covid-19 infection and 51% against the B.1.351 variant. The overall efficacy was 49% against Covid-19 and 43% against the B.1.351 variant, when people with HIV were included in the analysis.

In the UK study, the protection against Covid-19 Alpha variant (also called the UK or Kent variant, B.1.1.7) was 89%; but only 85% against severe disease.

Another variant, B.1.429, was first found in California and subsequently in at least 25 countries. The NVX-CoV2373 vaccine is effective against this variant. Against the described variants of concern and variants of interest, this vaccine’s efficacy is 93.2%.

Storage and Transport

NVX-CoV2373 is stable as a liquid formulation at 2°C to 8°C. This allows integration into existing cold chain procedures at most places. It can be stored in refrigerators available at most health facilities.

This is important since some of the Covid-19 vaccines require very low temperatures for storage and transport, making them difficult to deploy in resource-poor settings.

Value of the NVX-CoV2373 Covid-19 Vaccine

The USA already has three effective vaccines, and the country is on course to have enough doses to vaccinate every willing citizen. The FDA has indicated that they may not approve any more EUAs (emergency use authorization) and require full approval instead, which is a longer process.

This vaccine may still be of value for use as boosters when it is available for use. As more and more variants emerge and spread, we may need booster doses to maintain protection.

It may be especially valuable against variants of the Covid-19 virus. The efficacy figure of 90.4% was achieved in the spring, when the Alpha strain (also called B.1.1.7 or UK variant) was the dominant strain in the USA. The mRNA vaccines were both tested in 2020, when the original strain was in circulation.

Novavax has included proteins from the Beta strain ( also called B.1351 or South African variant) in a new version of this vaccine. When used as a booster in primates, it boosted immunity against Alpha, Beta, and the original Covid-19 (Wuhan) strain.

Covid-19 (SARS-CoV-2) has proved to be a formidable foe. The vaccines approved late last year offered a ray of hope of controlling the global pandemic. Unfortunately, the proliferating variants show immune escape, and even fully vaccinated people are developing severe disease.

Though NVX-CoV2373 has been able to complete trials much after the other vaccines, it may be a valuable weapon against the Covid-19 virus. It’s activity against the dominant variants and robust immune response raise hope for the future.


Heath PT et al. Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.1.7 Variant.

Keech C et al. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

Shinde V et al. Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant.

Whooley Sean. Novavax’s COVID-19 vaccine demonstrates 90% efficacy.

Xiaoying Shen et al. Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351

Zimmer Carl. Novavax Offers U.S. a Fourth Strong Covid-19 Vaccine.