Vaccine Info

Covaxin COVID-19 Vaccine

Authored by
Staff
Last reviewed
June 24, 2024
Share

Covaxin™ COVID-19 Vaccine Clinical Trials, Efficacy, Indication, Side Effects

Bharat Biotech (BBIL) Covaxin™ (BBV152) whole virion, inactivated COVID-19 vaccine is based on the Asp614Gly variant. It uses adjuvant Alhydroxiquim-II to boost immune response and longer-lasting immunity. The Indian Council of Medical Research created Covaxin in 2020 that contains six µg of whole-virion inactivated SARS-CoV-2 coronavirus antigen (Strain: NIV-2020-770) and other inactive ingredients such as aluminum hydroxide gel (250 µg), TLR 7/8 agonist (imidazoquinolinone) 15 µg, 2-phenoxyethanol 2.5 mg, and phosphate ® buffer saline up to 0.5 ml. The components of the Covaxin vaccine include BBV152A, BBV152B, and BBV152C. In addition, the virus strain is soaked in beta-propiolactone, an organic compound that deactivates them by binding to their genes, says the Company.

The SARS-CoV-2 betacoronavirus strain was isolated from an asymptomatic COVID-19 patient at India's National Institute of Virology. According to the U.S. Centers for Disease Control and Prevention (CDC), inactivated vaccines do not replicate and are unlikely to revert and cause pathological effects. The vaccine's adjuvant was developed with funding from the U.S. National Institutes of Health (NIH). The TLR7/8 adjuvant formulation induced significant Th1-biased antibody responses and increased SARS-CoV-2 lymphocyte responses.

On September 23, 2020, Bharat Biotech announced a licensing agreement with Washington University School of Medicine in St. Louis for a novel chimp adenovirus, a single-dose intranasal vaccine for COVID-19. In addition, on September 28, 2020, ViroVax LLC licensed its adjuvant, Alhydroxiquim-II technology, to Bharat Biotech to produce Covaxin. The indigenous inactivated vaccine was developed and manufactured in Bharat Biotech's facility in Genome Valley, Hyderabad, India.

The World Health Organization (WHO) granted an emergency use listing to Covaxin on November 3, 2021. On January 8, 2022, the Company reported the Covaxin induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least six months after vaccination. In addition, the WHO Strategic Advisory Group of Experts on Immunization (SAGE) issued updated interim policy recommendations for using the Covaxin vaccine on March 16, 2022. The SAGE recommends using Covaxin in two doses (0.5 ml) given intramuscularly, administered at an interval of 4 weeks. The WHO's SAGE recommends that severe and moderately immunocompromised persons be offered an additional dose of vaccine.

As of June 2024, Covaxin had been licensed in about 14 countries listed on this webpage. Covaxin (BBV152) Accession Number: DB15847; UNII: 76JZE5DSN6 Covaxin clinical trials are listed. BBIL posted on X on June 22, 2024, that the Company unintentionally omitted the ICMR as a co-owner of the inactivated COVAXIN® vaccine patent. The ICMR was to receive a 5% royalty on net sales and product branding rights, which include 'co-inventor' status.

Hyderabad-based Bharat Biotech creates innovative vaccines and bio-therapeutics trusted by physicians worldwide. Chiron Behring Vaccines became a subsidiary in 2019. The indigenous, inactivated COVID-19 vaccine is manufactured in Bharat Biotech's Bio-Safety Level 3 high containment facility.

Covaxin - Ocugen Inc. Agreement

Ocugen, Inc., a Pennsylvania-based biopharmaceutical company, and India-based Bharat Biotech announced on February 2, 2021, that they entered a definitive agreement to co-develop, supply, and commercialize COVAXIN in the U.S. On June 3, 2021, the companies amended their Co-development agreement to expand Ocugen's territory to commercialize COVAXIN in Canada. In addition, the Company announced the completion of its regulatory submission to Health Canada for COVAXIN, conducted through Vaccigen, Ltd. The companies amended their agreement on April 18, 2022, empowering Ocugen with full commercial rights to North America, including Mexico.

On October 27, 2021, Ocugen submitted an Investigational New Drug application to the FDA. And on November 5, 2021, Ocugen applied for pediatric use in the U.S. On November 26, 2021, Ocugen announced that the FDA issued a clinical hold on the Company's IND. This Hold was removed on February 18, 2022. However, on April 12, 2022, the Company announced that the FDA informed that the agency placed its Phase 2/3 immuno-bridging and broadening study OCU-002 on clinical Hold. Results from the Company's decision to voluntarily implement a temporary pause in dosing participants of OCU-002 while it evaluates statements made by the WHO on April 4, 2022.

On September 14, 2022, Ocugen, Inc. announced the publication "A comprehensive review of BBV152 vaccine development, effectiveness, safety, challenges, and prospects." On August 5, 2022, Ocugen Inc. confirmed the Phase 2/3 immuno-bridging and broadening clinical trial, OCU-002, for COVAXIN™ is progressing well, and the Company is actively engaged in planning for the initiation of an adult safety clinical trial this year. COVAXIN™ Data Published in Scientific Journals – In June 2022, positive pediatric Phase 2/3 study results in children aged 2-18 were published in The Lancet Infectious Diseases. In addition, a study published in Nature Scientific Reports in July shows that COVAXIN™ (BBV152) generated a persistent cell-mediated memory immune response for up to 12 months. 

On January 9, 2023, Ocugen announced positive results from Phase 2/3, observer-blind, immuno-bridging, and broadening the clinical study of COVAXIN™ (NCT05258669). The study met both co-primary endpoints with robust immune responses, and COVAXIN™ was found to be well-tolerated in vaccine-naïve individuals and individuals previously vaccinated with mRNA vaccines in the U.S., with no vaccine-related serious adverse events, thrombotic events, or cases of myocarditis or pericarditis.

Covaxin Vaccine Boosters

The companies announced results from a study conducted at Emory University on January 12, 2022, demonstrating sera from people who received a booster dose of candidate vaccine COVAXIN six months after getting a primary two-dose series neutralized SARS-CoV-2 coronavirus variants. A previous, non-peer-reviewed study published on January 8, 2022, found participants receiving a booster dose six months after the second dose of COVAXIN™ saw a significant increase (>10-fold across Alpha, Beta, Delta, and Delta Plus variants) in neutralizing titers compared to baseline at six months. The WHO confirmed its support for 3rd-dose booster vaccinations for certain people on March 16, 2022. Japan approved COVAXIN boosters effective from July 31, 2022.

Covaxin Indication

Covaxin is indicated for specific populations against SARS-CoV-2 coronavirus infection to prevent severe disease. A peer-reviewed study published on February 11, 2022, found that 'precaution needs to be taken while vaccinating individuals having allergies, comorbidities, acute infection in the last three months and individuals on chronic medications.' The WHO reported on March 16, 2022, that the SAGE has thoroughly assessed the data on the safety and efficacy of the vaccine and has recommended its use for people aged 18 and above.

Covaxin Side Effects

Whole virion-inactivated vaccines have proven safe and tolerable, with a safety track record of several decades. Side effects reported with COVAXIN (BBV152) include but are not limited to Injection site pain, Swelling, Redness, Itching, Headache, Fever, Malaise/body ache, Nausea, Vomiting, and Rashes. A severe allergic reaction very rarely occurs after getting a dose of COVAXIN. However, severe and unexpected side effects may occur. A study by Sankha Shubhra Chakrabarti and a team at Banaras Hindu University published in May 2024 found that the most effects persisted at the 1-year follow-up. In January 2022, a phase 2, double-blind, randomized controlled COVAXIN trial demonstrated long-term safety with about 1% serious adverse events.

Covaxin Vaccine Dosage

BBV152 is administered in two intramuscular doses of 6 µg of inactivated virus four weeks apart. Covaxin is formulated uniquely so that the exact dosage can be administered for primary and booster doses. It is distributed in a ready-to-use liquid vaccine stored at 2-8C, with a 12-month shelf life and a multi-dose vial policy.

Covaxin Vaccine News

June 22, 2024 - BBIL posted Covaxin contract issues on X / Twitter.

April 14, 2023 - Media in India indicated Covaxin production would restart based on new orders.

June 9, 2022 - The WHO published BBV152 COVAXIN vaccine against COVID-19: What you need to know.

June 1, 2022 - Germany began recognizing Covaxin as valid for entry into the country in June 2022.

May 23, 2022 - Ocugen, Inc. announced that the U.S. FDA lifted the clinical Hold on the Company's Phase 2/3 clinical trial, OCU-002, for COVAXIN™ (BBV152).

April 26, 2022 - India health minister Mansukh Mandaviya tweeted - Bharat Biotech's Covaxin has been granted emergency use permission for the six-12 age group,

April 18, 2022 - Ocugen gained commercialization rights for COVAXIN in North America.

April 12, 2022 - Ocugen, Inc., announced that the U.S. FDA had placed a Clinical Hold on its Phase 2/3 clinical study.  

January 12, 2—Ocugen, Inc. and Bharat Biotech issued a press release stating that a booster (3rd) dose of COVAXIN generated robust neutralizing antibody responses against both Omicron (B.1.529) and Delta (B.1.617.2) using a live virus neutralization assay. 100% of test serum samples in the phase 1/2 study showed neutralization of the Delta variant, and more than 90% of serum samples showed neutralization of the Omicron variant.

November 23, 2021 - This study published by The Lancet is, to our knowledge, the first real-world observational study assessing the vaccine effectiveness of BBV152. We found vaccine effectiveness to be 50% (95% CI 33–62) for complete vaccination at least 14 days before testing against symptomatic laboratory-confirmed COVID-19. 

November 22, 2021 - The U.K. added the Covaxin vaccine to its travel approval list, requiring at least 14 days of immunization before arriving in England.

November 11, 2021 - The Lancet published a study: Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomized, double-blind, controlled, phase 3 trial. Findings: 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2–86·4).

February 2, 2021 - Ocugen, Inc. and Bharat Biotech announced they have entered into a definitive agreement to codevelop, supply, and commercialize a COVID-19 vaccine candidate for the U.S. market.

May 8, 2020 - The Council of Scientific and Industrial Research, under its flagship program NMITLI, sanctioned a project to develop human monoclonal antibodies as therapy for COVID-19 infections. The project is being led by Bharat Biotech, a leading manufacturer of vaccines and biotherapeutics and a product supplier to over 65 globally.

Covaxin Clinical Trials

Covaxin continues to be tested in various clinical trials.

Ocugen announced on January 9, 2023, positive results from the 2/3, observer-blind, immuno-bridging, and broadening the clinical study of COVAXIN™ (NCT05258669). On January 23, 2023, the peer-reviewed Lancet Regional Health South East journal published results from a study that concluded homologous and heterologous boosting with COVISHIELD™ or COVAXIN in COVISHIELD or COVAXIN primed individuals are immunogenic and safe. A heterologous boost with COVISHIELD after COVAXIN® prime offers the best immune response. On September 14, 2023, a study reported that polyfunctional CD4 T-cells correlating with neutralizing antibodies are a hallmark of COVISHIELDTM- and COVAXIN®-induced immunity in COVID-19.

The peer-reviewed journal Nature Microbiology published on June 9, 2022: Inactivated whole-virion vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern. 'Found that antigen-specific CD4+ T cells were present in the central memory compartment and persisted for at least six months post-vaccination. In addition, vaccine-induced CD8+ T cells were detected in ~50% of individuals. Importantly, the vaccine could induce follicular T helper cells that exhibited B-cell help potential. These findings show that inactivated vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern that persist for at least six months after vaccination.' On June 16, 2022, The Lancet published results from a phase 2/3 study that found Covaxin BBV152 was well tolerated in children aged 2–18 years and induced higher neutralizing antibody responses than those observed in adults.

The peer-reviewed journal Frontiers in Immunology, published on September 13, 2022: A comprehensive review of BBV152 vaccine development, effectiveness, safety, challenges, and prospects. The BBV152 booster given six months after complete vaccination reverses a waning immunity and restores the neutralization efficacy. It shows synergy in a heterologous prime-boost study with about a 300% increase in neutralization titers against multiple SARS-CoV-2 variants of concern. In addition, @BharatBiotech announced on December 17, 2022, the journal Cell / iScience published study results that show that administration of a COVAXIN booster dose enhances the vaccine effectiveness against the Delta variant infection and enhances protection against the BA.1.1 and BA.2 virus variants.

March 8, 2021 - The Lancet reported: The BBV152 vaccine, adjuvanted with alum and a TLR 7/8 agonist, is designed to enhance humoral and Th1-skewed cellular immune responses after immunization by optimizing the inactivated vaccine formulation. Overall, Algel-IMDG-adjuvanted BBV152 was safe, immunogenic, and able to induce Th1-biased T-cell responses and could be a potentially superior vaccine over the alum-adjuvanted inactivated COVID-19 vaccines. However, this is the only study of an inactivated COVID-19 vaccine candidate to report a thorough evaluation of cell-mediated responses. Therefore, the 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial.

ClinicalTrials: NCT05258669 - Immuno-bridging and Broadening Study of a Whole, Inactivated COVID-19 Vaccine BBV152 in Healthy Adults. Last Update Posted: August 31, 2022.

Clinical Trials: NCT05049187 - Observational study to determine the characterization and durability of COVID-19 Vaccine-induced immunity responses in Healthcare/Frontline Workers

Clinical Trial: NCT04918797 - Phase 2/3 COVAXIN in a Pediatric Cohort (COVAXIN-Peds) study was last updated on July 2, 2021.

Clinical Trial: NCT04641481 - An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers.

Clinical Trial: NCT04471519 - Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers (BBV152). The total sample size was 755 healthy volunteers, with 375 and 380 volunteers in phase 1 and 2 studies, respectively.