Adjuvant developed with NIH funding enhances efficacy of India’s COVID-19 vaccine

Dr. Rajesh Jain

3 years ago

Adjuvant developed with NIH funding enhances the efficacy of India’s COVID-19 vaccine.

The adjuvant used in the COVID-19 COVAXIN vaccine, Alhydroxiquim-II, was discovered and tested in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas, with support exclusively from the NIAID Adjuvant Development Program. The adjuvant comprises a small molecule attached in a unique way to Alhydrogel; a substance frequently called alum is the most commonly used adjuvant in vaccines for people. Alhydroxiquim-II travels to lymph nodes, where the small molecule detaches from the alum and activates two cellular receptors. These receptors, TLR7 and TLR8, play a vital role in the immune response to viruses. Alhydroxiquim-II is the first adjuvant in an authorized vaccine against infectious disease to activate TLR7 and TLR8. In addition, the alum in Alhydroxiquim-II stimulates the immune system to search for an invading pathogen.

This scanning electron microscope image shows SARS-CoV-2 (round gold particles) emerging from the surface of a cell cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19.NIAID

Molecules that activate TLR receptors stimulate the immune system powerfully, but the side effects of Alhydroxiquim-II are mild. This is because, after COVAXIN is injected, the adjuvant travels directly to nearby lymph nodes, which contain white blood cells that play an essential role in identifying pathogens and fighting infection. Consequently, only a small amount of Alhydroxiquim-II is needed in each dose of vaccine, and the adjuvant does not circulate throughout the body, thereby averting more widespread inflammation and undesirable side effects.

COVAXIN comprises a disabled form of SARS-CoV-2 that cannot replicate but still stimulates the immune system to make antibodies against the virus. Published results(link is external) from a Phase 2 trial of the vaccine indicate that it is safe and well-tolerated. Safety data from a Phase 3 trial of COVAXIN in 25,800 participants in India will become available later this year. Meanwhile, unpublished interim results from the Phase 3 trial indicate that the vaccine has 78% efficacy against symptomatic disease, 100% efficacy against severe COVID-19, including hospitalization, and 70% efficacy against asymptomatic infection SARS-CoV-2, the virus that causes COVID-19. Results from two(link is external) studies(link is external) of blood serum from people who had received COVAXIN suggest that the vaccine generates antibodies that effectively neutralize the B.1.1.7 (Alpha) and B.1.617 (Delta) variants of SARS-CoV-2, first identified in the United Kingdom and India, respectively.

The NIAID Adjuvant Program has supported the research of the founder and chief executive officer of ViroVax―Sunil David, M.D., Ph.D.―since 2009. His work has focused on searching for novel molecules that activate innate immune receptors and developing them as vaccine adjuvants.

The collaboration between Dr. David and the company that makes COVAXIN, Bharat Biotech International Ltd. of Hyderabad, was initiated during a 2019 meeting in India coordinated by the NIAID Office of Global Research under the auspices of NIAID’s Indo-U.S. Vaccine Action Program. A delegation of five NIAID-funded adjuvant investigators, including Dr. David; two members of the NIAID Division of Allergy, Immunology, and Transplantation; and the NIAID India representative visited four leading biotechnology companies to learn about their work and discuss potential collaborations. The delegation also attended a consultation in New Delhi co-organized by NIAID and India’s Department of Biotechnology and hosted by India’s National Institute of Immunology.

Among the scientific collaborations sparked by these activities, Bharat Biotech signed a licensing agreement with Dr. David to use Alhydroxiquim-II in their candidate vaccines. This license was expanded during the COVID-19 pandemic to include COVAXIN, which has received Emergency Use Authorization in India and more than a dozen other countries. Bharat Biotech developed COVAXIN in collaboration with the Indian Council of Medical Research ‒ National Institute of Virology. The company conducted extensive safety studies of Alhydroxiquim-II and undertook the complex process of scaling up production of the adjuvant under Good Manufacturing Practice standards. Bharat Biotech expects to produce an estimated 700 million doses of COVAXIN by the end of 2021.

NIAID conducts and supports research at NIH throughout the United States and worldwide to study the causes of infectious and immune-mediated diseases and develop better means of preventing, diagnosing, and treating these illnesses. News releases, fact sheets, and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research investigating the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health

Countries around the world are now racing to vaccinate people against SARS-CoV-2, the virus that causes COVID-19. It is one of the most ambitious vaccination programs ever.

Two of the vaccines being used in the U.S.—produced by Pfizer-BioNTech and Moderna—require two doses that are given several weeks apart. Small studies have suggested that people who previously had COVID-19 may get a strong immune response from only one dose of these vaccines. If such people get immunity from a single dose, that could free up more shots for others.

To look at this question in a larger group of people, researchers led by Drs. Jonathan Braun, Susan Cheng, and Kimia Sobhani from Cedars-Sinai Medical Center used blood samples donated by healthcare workers at their hospital. The team measured levels of antibodies in the blood before vaccination and then after each of the two vaccine doses. They compared levels in people with prior COVID-19 infection with those who never had the virus. Blood samples were taken between 7 and 21 days after each vaccination.

The study was funded by NIH’s National Cancer Institute (NCI) and National Heart, Lung, and Blood Institute (NHLBI). Results were published on April 1, 2021, in Nature Medicine.