Bharat Biotech's Covaxin™ (BBV152) whole virion, inactivated COVID-19 vaccine is based on the Asp614Gly variant. that uses adjuvant Alhydroxiquim-II to boost immune response and longer-lasting immunity. The Indian Council of Medical Research created the COVAXIN vaccine 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.
Covaxin is formulated uniquely such that the exact dosage can be administered to adults and children for primary and booster doses, distributed in a ready-to-use liquid vaccine, stored at 2-8C, with 12 months shelf life and multi-dose vial policy. In addition, whole virion-inactivated vaccines have proven safe and tolerable, with a safety track record of several decades.
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) and has contributed to the success of the highly efficacious COVAXIN COVID-19 vaccine. The TLR7/8 adjuvant formulation induced significant Th1-biased antibody responses and increased SARS-CoV-2 lymphocyte responses.
The World Health Organization (WHO) granted an emergency use listing to COVAXIN on November 3, 2021. On January 8, 2022, the company reported the inactivated virus vaccine BBV152 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 Bharat Biotech BBV152 COVAXIN vaccine on March 16, 2022. The SAGE recommends using the BBV152 vaccine in two doses (0.5 ml) given intramuscularly, administered at an interval of 4 weeks. And SAGE recommends that severe and moderately immunocompromised persons be offered an additional dose of vaccine.
The peer-review 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, restores the neutralization efficacy, and 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.
The U.S. Food and Drug Administration (FDA) lifted its clinical Hold on the Company's Investigational New Drug application to evaluate COVAXIN on February 18, 2022. On April 12, 2020, the FDA issued a second clinical hold. Soumya Swaminathan, Chief Scientist at the WHO, assured that the freeze on the Covaxin vaccine supply does not involve the safety or efficacy of the vaccine as of April 21, 2022. Accordingly, on May 23, 2022, the FDA removed its clinical Hold.
On January 23, 2023, the peer-review 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 among the four combinations evaluated.
As of January 26, 2023, Covaxin had been licensed for use in about 25 countries, such as Germany, Malaysia, Mauritius, Mexico, and others listed on this webpage. More than 350 million doses have been administered to adults outside the U.S.. Additionally, as many as 85 countries have agreed to mutual recognition of COVID-19 vaccination certificates with India that includes vaccination using COVAXIN™.
Covaxin (BBV152) Accession Number: DB15847; UNII: 76JZE5DSN6 Covaxin clinical trials are listed. As of April 2022, about 350 million Covaxin doses had been distributed worldwide.
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.
iNCOVACC® Nasal Vaccine
iNCOVACC® (ChAd-SARS-CoV-2-S) (BBV154) is a recombinant replication-deficient adenovirus vectored vaccine with a prefusion stabilized spike protein. The nasal delivery system was developed in partnership with Washington University in St. Louis, Missouri. The BBV154 intranasal vaccine stimulates a broad immune response – neutralizing IgG, mucosal IgA, and T-cell responses essential for blocking infection and transmission of the SARS-CoV-2 coronavirus.
Covaxin - Ocugen Inc.
Ocugen, Inc., a Pennsylvania-based biopharmaceutical company, and India-based Bharat Biotech announced on February 2, 2021, that they entered into 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, which was conducted through Vaccigen, Ltd. On April 18, 2022, the companies amended their agreement empowering Ocugen with full commercial rights to North America, including Mexico.
The Company confirmed on May 6, 2022, that it is actively engaged in discussions with the U.S. FDA to address its questions and resume the Company's Phase 2/3 immuno-bridging and broadening clinical trial for COVAXIN™, OCU-002. In addition, the Company intends to continue working with the FDA to finalize the additional studies required for a Biologics License Application. 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. This is a result of 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 November 8, 2022, Ocugen announced enrollment was completed, and Covaxin dosing continues in the immuno-bridging and broadening Phase 2/3 clinical trial. No safety concerns have been identified, and efficacy is being continuously monitored. Top-line data is expected in early 2023.
On January 9, 2023, Ocugen announced positive results from the Phase 2/3, observer-blind, immuno-bridging, and broadening 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 Price
On April 9, 2022, @BharatBiotech announced Covaxin would be available for Rs 225 per dose. However, the Mint reported on January 26, 2022, that the price of the Covaxin vaccine is likely to be capped at ₹275 per dose plus an additional service charge of ₹150. Different vaccine price and discount information is posted at InstantRx™.
Covaxin Omicron Sublineages
The National Institute of Virology in India conducted a hamster study that concluded, "In the vaccine efficacy study against the Omicron variants BA.1 and BA.2, lesser virus shedding, viral lung load, and lung disease severity were observed in the immunized groups in comparison to the placebo groups. Furthermore, a related study found booster dose vaccinations enhance the neutralizing antibody responses against homologous and heterologous variants.'
Ocugen, Inc. and Bharat Biotech announced on January 12, 2022, results from a phase 1/2 clinical study conducted at Emory University in Georga demonstrating that sera from subjects who received a booster dose of candidate vaccine COVAXIN six months after getting a primary two-dose series of COVAXIN neutralized the SARS-CoV-2 Omicron and Delta variants. Earlier studies demonstrated the neutralizing potential of COVAXIN™ (BBV152) against SARS-CoV-2 Variants of Concern Alpha, Beta, Delta, Zeta, and Kappa.
The Coalition for Epidemic Preparedness Innovations announced on May 10, 2022; it would provide funding of up to US$19.3 million to support the development of a 'variant-proof' SARS-CoV-2 vaccine candidate to an international multidisciplinary consortium comprising Bharat Biotech International Ltd., the University of Sydney, and ExcellGene SA, Switzerland.
The companies announced results from a study conducted at Emory University on January 12, 2022, demonstrating that 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.
A non-peer-reviewed research paper announced on March 9, 2022, that despite a weakening in antibody response after six months, those in the heterologous study group who were given one dose of Covishield and a second dose of Covaxin six weeks apart showed a better immune response than people who were given either Covishield or Covaxin as both doses.
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.
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 Bio-Biotech'svel 3 High-Containment facility in Genome Valley, Hyderabad, India.
Covaxin is indicated for certain people for protection against SARS-CoV-2 coronavirus infection risk and severe COVID-19 prevention. 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.
As of March 16, 2022, the WHO recommends using BBV152 in pregnant women when the benefits of vaccination outweigh the potential risks. The WHO does not recommend pregnancy testing before vaccination. And data are unavailable on the potential benefits or risks of the BBV152 vaccine to breastfed children. However, as the BBV152 vaccine is not a live virus vaccine, it is biologically unlikely to threaten the breastfeeding child.
Covaxin has proven to be a highly safe vaccine based on data from more than 50 million doses administered to children in India. On June 16, 2022, the peer-review journal The Lancet published a study: Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2–18 years: interim data from an open-label, non-randomized, age de-escalation phase 2/3 study - that shows Covaxin is equally well tolerated and immunogenic in seronegative children aged 2–18 years. No adverse events of special interest have been reported to date.
As of April 12, 2022, in Madurai, India, around 87% of children aged 17 had taken one dose, with no side effects reported. On March 16, 2022, the WHO stated that the safety and immunogenicity data for under-18s are currently being generated. However, vaccination of individuals in this age group is not recommended until such data are available.
On December 25, 2021, Covaxin was approved for 12 and 18-year-olds by the Drugs Controller General of India. At the request of the U.S. FDA, Ocugen shared real-world safety data from 36 million teenagers vaccinated with COVAXIN. Additionally, data (in-vitro) suggesting robust neutralization against Delta and Omicron variants were submitted to bolster the Company's pediatric EUA submission.
There is not enough data at present (Mar. 16, 2022) to assess the efficacy or safety of this vaccine for people living with HIV. In the interim, however, given that the vaccine is nonreplicating, people living with HIV that are stable may be vaccinated with the standard primary series of 2 doses.
Covaxin Side Effects
Data from over 50 million doses given to children in India reveals minimal side effects. A phase 2, double-blind, randomized controlled COVAXIN trial demonstrated long-term safety with no serious adverse events as of January 8, 2022. 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, Rashes. A severe allergic reaction may very rarely occur after getting a dose of COVAXIN. However, serious and unexpected side effects may occur.
On July 2, 2021, a non-peer-reviewed study found the 'BBV152 vaccine was well tolerated with no clinically or statistically significant differences in the distributions of solicited, unsolicited, or serious adverse events between vaccine and placebo groups.' Adverse events reported were similar to placebo, with 12.4% of subjects experiencing commonly known side effects and less than 0.5% feeling serious adverse events. A case report was published on September 12, 2021: Recurrent herpes zoster after COVID-19 vaccination in three patients with chronic urticaria treated with cyclosporine.
BBV152 is administered in two intramuscular doses of 6 µg of inactivated virus four weeks apart.
January 9, 2023 - Dr. Shankar Musunuri, Chairman, CEO, and Co-Founder of Ocugen stated: “Given that a portion of the public remains hesitant to receive mRNA vaccines, this investigational COVID-19 vaccine candidate, which relies on a well-established approach to vaccine development and manufacturing, may provide an important additional vaccine option.”
November 3, 2022 - Media sources indicate Bharat Biotech may waste 200 million doses of Covaxin in bulk form due to expiration dates in 2023.
September 6, 2022 - Dr. Krishna Ella, Chairman & Managing Director, Bharat Biotech, commented, "We are proud to announce the approval of iNCOVACC, a global game changer in Intra Nasal vaccines technology and delivery systems. We thank the Ministry of Health, the CDSCO, the Dept of Biotechnology Govt of India, and Washington University St. Louis for their support and guidance."
August 22, 2022 - "In summary, based on the said CAPA response, the manufacturing site for Covaxin is still considered to be operating at an unacceptable level of compliance with WHO Good Manufacturing Practices for Pharmaceutical Products guidelines," WHO told The Wire.
August 10, 2022 - Japan's Ministry of Health, Labour, and Welfare added Covaxin to its approved vaccine list for travelers.
July 15, 2022 - The journal AJMC published results from a study based in India: Clinical Profile of COVID-19 Infection in Postvaccination Individuals. Findings: The study shows a significant reduction in the requirement of hospitalization among vaccinated individuals and a 50% higher chance of having mild disease after two doses of vaccination than after a single dose.
July 14, 2022 - A comprehensive report on the immunogenicity of COVAXIN® booster dose against ancestral and Variants of Concern up to 12 months - clinical study results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants.
June 21, 2022 - Dr. Krishna Ella, Chairman and Managing Director of Bharat Biotech, said in a press statement, "We have now achieved our goal of developing a safe and efficacious COVID-19 vaccine for adults and children for primary immunization and booster doses, making Covaxin a universal vaccine. It has proven to be a highly safe vaccine based on data from more than 50 million doses administered to children in India."
June 16, 2022 - The Lancet published results from a phase 2/3 study - the inactivated SARS-CoV-2 vaccine BBV152 was well tolerated and immunogenic in children aged 2–18.
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.
April 2, 2022 - The WHO announced vaccine supply disruption following a manufacturing facility inspection. This suspension is in response to the outcomes of the WHO post-EUL inspection (14 – 22 March 2022) and the need to conduct process and facility upgrades to address recently identified GMP deficiencies.
January 12, 2022 - Ocugen, Inc. and Bharat Biotech issued a press release stating 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; and 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.
December 30, 2021 - Ocugen, Inc. announced Bharat Biotech posted results on (Dec. 29) from a Phase 2/3 trial conducted in India of COVAXIN in children aged 2 – 18 years, demonstrating a robust neutralizing antibody response and favorable safety profile.
December 3, 2021 - India's approved the shelf life of COVID-19 vaccines Covaxin to 12 months.
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 of 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).
July 3, 2021 - Bharat Biotech announced safety and efficacy analysis data today from Phase III clinical trials of COVAXIN. Efficacy analysis demonstrates COVAXIN® to be 93.4% effective against severe symptomatic COVID-19. And Efficacy data demonstrates 65.2% protection against the SARS-CoV-2, B.1.617.2 Delta variant.
May 3, 2021 - Scientists at the Indian Council of Medical Research-National Institute of Virology have found that Covaxin is effective against the Brazil variant, B.1.128.2. This finding comes after their study that suggested that Covaxin was effective against the U.K. variant and the Indian (double mutant) variant B.1.617.
March 2, 2021 - The journal Nature published a study: Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Altogether, this study demonstrates that a two-dose vaccination regimen using a 3-µg dose of the vaccine candidate with adjuvant B induces a significant immune response and provides effective protection in animals challenged with SARS-CoV-2.
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.
July 15, 2020 - Bharat Biotech announced the Phase-I clinical trialsIntrialsIndia'sitrialsIndia'sia'sous9 vaccine, Covaxin, began across the country, enrolling 385 people in 12 hospitals.
June 29, 2020 - India's India'snCovaxiIndia'seceivedion to initiate Phase I & II Human clinical trials after the Company submitted results from preclinical studies, demonstrating safety and immune response.
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.
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. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial. BBV152 (developed using a well-established manufacturing platform) was safe, immunogenic (persisting for 3 months), and stored at 2–8°C, compatible with most immunization cold chain requirements countries. Follow-up studies to assess the efficacy and immune responses in older adults and people with comorbidities are underway.
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). A total sample size of 755 healthy volunteers, with 375 and 380 volunteers in phase 1 and 2 studies, respectively.