CorbeVax® COVID-19 Vaccine March 2023

Biological E. Limited CorbeVax® COVID-19 Vaccine (BioE COVID-19, BECOV2D) is based on classical a protein subunit vaccine technology of a protein antigen, SARS-CoV-2 Spike receptor-binding domain (RBD), adsorbed to the adjuvant Alhydrogel (Alum), in combination with another approved adjuvant, CpG 1018. CorbeVax uses a harmless piece of the spike protein to stimulate and prepare the human immune system for future encounters with the beta coronavirus.

The Biological E. RBD of the S1 subunit binds to the Angiotensin-Converting Enzyme-2 (ACE2) receptor on the host cell membrane targeting SARS-CoV-2 virus entry mechanisms. The Baylor College of Medicine developed construct "RBD N1C1" was selected as the final vaccine antigen candidate based on its manufacturability due to the yields of protein antigen achieved, ease of process steps, and favorable formulation aspects, and is similar to Bio E's technology for large-scale commercial production of vaccines. The protein is expressed in yeast Pichia pastoris. The vaccine antigen's initial construct and production process were developed at Texas Children's Hospital in Houston, Texas, led by co-directors Drs. Maria Elena Bottazzi and Peter Hotez and in-licensed from BCM Ventures. In addition, Texas Children's Hospital CVD received philanthropic support for developing this vaccine from donors, including a significant contribution from The JPB Foundation in May 2020.

Combining Alum with Dynavax Technologies Corporation's CpG with N1C1 antigen elicited a highly synergistic, balanced immune response in preclinical models. Four formulations with these components are currently being evaluated in India's Phase I/II clinical study to select the final vaccine candidate to be tested in subsequent studies. Potential advantages of this vaccine include scalability and thermostability, which could make it suitable for deployment in low-resource countries.

Biological E. announced on February 21, 2022, that the CorbeVax vaccine received emergency use authorization (EAU) from India's Drugs Controller General of India (DCGI) for the 12 to 18-year age group. And for the 12-14 age group was approved on March 17, 2022. In addition, the Subject Expert Committee (SEC) recommended granting emergency use authorization to Corbevax for children aged five to 11 years with certain conditions on April 21, 2022. The DCGI approved CorbeVax for restricted use in emergencies among adults on December 28, 2021. On June 4, 2022, the DCGI approved CorbeVax as a heterologous COVID-19 booster dose for adults fully vaccinated either with Covishield or Covaxin, as confirmed by the Union health ministry.

On August 12, 2022, The Lancet published the optimum formulation in open-label, multicentre, and randomized phase-1/2 and phase-2 clinical trials. Corbevax (two-dose schedule with 28 days of intervals between doses) was well tolerated with no observed safety concerns. Previous observations from efficacy studies by Moderna and AstraZeneca and the correlation between nAb titres post-vaccination and a human convalescent serum panel showed that Corbevax induced significantly high nAb titres.

 In addition, the Company publishes Package Insert, FAQs, Fact Sheets, and ATC Code: J07BX03. As of January 12, 2023, the U.S. Food and Drug Administration (FDA) had not authorized the CorbeVax vaccine for use in the U.S.

Hyderabad-based Biological E. Limited (BE) is a Pharmaceuticals & Biologics Company founded in India in 1953. It is the first private-sector biological products company in India and the first pharmaceutical company in Southern India. BE supplies its vaccines to over 100 countries. BE currently has eight WHO-prequalified vaccines in its portfolio. BE started its journey in vaccine manufacturing in the year 1962. On July 22, 2022, Biological E announced an investment of over Rs 1,800 crore toward expanding its facilities and operations in Hyderabad. BE has about 1,500 people working at facilities.

CorbeVax Bivalent Vaccine

"Biological E has started the development of a bivalent vaccine based on the receptor binding domain protein antigen of the ancestral strain as well as the BA.5 strain," Vikram Paradkar, executive vice president of Biological E, told ET on January 3, 2023.

CorbeVax Booster

The peer-review journal Vaccines published a study on December 14, 2022, that showed both homologous (Covishield priming Covishield boosting) and heterologous boosters (Covishield priming Corbevax boosting) induce strong SARS-CoV-2 S1/S2 spike IgG antibody responses. The data shows the RBD-specific antibody response was much greater with Corbevax administered as a heterologous booster after two doses of Covishield, probably due to the protein nature of the vaccine. Additionally, the study also demonstrates increased CD4 T lymphocyte responses sustaining up to 90 days and beyond in individuals receiving Corbevax as a heterologous booster. The longer duration of CD4 T lymphocyte responses with Corbevax indicates protection for a longer period of time with the heterologous booster dose as compared to the homologous booster. Upon exposure to the virus, CD4 T lymphocytes activate B lymphocytes and CD8 T lymphocytes and provide protection against infection.

A non-peer-reviewed study published on January 3, 2023, demonstrates a significant benefit of giving CORBEVAX™ heterologous booster dose to subjects that have received COVISHIELD™ or COVAXIN primary vaccination; as early as 6 months after post the second dose of primary vaccination.

With the recommendation of India's NTAGI, Corbevax has been included as a heterologous precaution dose in the National COVID-19 Vaccination program, which can be taken after the second dose of either Covaxin or Covishield. The Precaution 'booster' dose can now be taken 26 weeks after the second dose.

BE conducted a multicentre Phase III placebo-controlled heterologous booster clinical trial in 416 subjects from 18 to 80 years of age who were previously vaccinated with two doses of either COVISHIELD or COVAXIN at least six months before the administration of CORBEVAX as a booster dose. The booster dose of CORBEVAX increased the neutralizing antibody titers in the COVISHIELD and COVAXIN groups significantly compared to the placebo. In addition, in a subset of subjects evaluated for nAb against the Omicron variant, the CORBEVAX  booster shot significantly increased the nAb titers against the Omicron variant. After the booster dose of CORBEVAX, Omicron nAbs were observed in 91% and 75% of subjects who had received primary vaccination by COVISHIELD and COVAXIN, respectively. The booster dose also resulted in a significant Th1 skewed cellular immune response as indicated by cytokine expression analysis post-stimulation of the T-cells.

CorbeVax Price

Biological E. Limited announced on May 16, 2022, that it had reduced the price of CORBEVAX from Rs.840 to Rs.250 a dose, including GST, for Private COVID-19 Vaccination Centres. For the end-user, the cost would be Rs.400 a dose, including taxes and administration charges. Additional vaccine price and discount information is posted at InstantRx™.

CorbeVax Availability

As of March 28, 2023, the CorbeVax vaccine was available in India and Botswana. As of December 2022, 1,973,313 Corbevax doses have been deployed. BE has supplied about 100 million doses to the Government of India and has been administered to children, including 17.4 million who have completed the two-dose regimen. Media reported the WHO intends to Prequalification List CorbeVax in 2023.

CorbeVax SARS-CoV-2 Variant Sublineages

The SARS-CoV-2 virus has undergone mutations in a short duration. In clinical trials, CORBEVAX-induced immune response demonstrated consistent neutralization of the Ancestral SARS-COV-2 strain and the Variants of Concern such as Beta, Delta, and Omicron. Given its recent designation, Omicron/B.1.1.529 therapeutic activity data is currently being reported rapidly. As of August 4, 2022, the U.S. NIH OpenData Portal is working to ingest all applicable in vitro activity data for Omicron. However, Omicron data should be interpreted with caution.

CorbeVax Adolescents

On November 3, 2022, Biological E. Limited announced the journal Vaccine published a study that found CORBEVAX vaccinated subjects showed significant immune response against Ancestral-Wuhan and Delta-strains. Cytokine Interferon-gamma expression analysis showed a significant Th1 skewed cellular immune response generated from CORBEVAX. And there were no severe adverse events reported.

According to the India Union Ministry of Health and Family Welfare as of April 1, 2022, Corbevax is available for adolescents aged 12-14 and was approved based on its interim safety and immunogenicity data. Corbevax is the only COVID-19 vaccine approved in India for this age group. CorbeVax vaccination appointments in India can be scheduled at this CoWIN weblink. In Madurai, 69,528 children were vaccinated, accounting for 78% coverage for the first dose as of April 12, 2022. No cases of adverse reactions have been reported.

CorbeVax Indication

The CorbeVax COVID-19 Vaccine candidate is indicated to prevent COVID-19, a disease caused by the SARS-CoV-2 beta coronavirus. Instead of the entire pathogen, subunit vaccines include only the components, or antigens, that best stimulate the immune system. Although this design can make vaccines safer and easier to produce, it often requires the incorporation of adjuvants to elicit a strong protective immune response because the antigens alone are not sufficient to induce adequate long-term immunity, says the US NIH.

CorbeVax Dosage

For eligible children, adolescents, and adults in India, two doses, separated by 28 days, are authorized. According to the Corbevax phase 2/3 clinical trial, 624 children participated. Media reports that efficacy data is pending. The vaccine is stored at 2 to 8 degrees Celsius.

eBioMedicine reported on August 12, 2022, all formulations showed similar profiles of humoral and cellular immune responses that were associated with the content of CpG1018 adjuvant in the vaccine. In the Phase-2 study, 750 µg of CpG1018 showed significant improvement (> 4-fold increase from baseline) in immune responses, including the titres of anti-RBD IgG and neutralizing antibody (nAb) and cellular immune responses, while maintaining the safety profile. Antibodies persisted consistently for 12 months after the second dose of the vaccine.

Biological E. Limited and Jcovden COVID-19 Production

The U.S. Embassy in India tweeted on June 21, 2022, "Congratulations to @biological_e on its WHO approval as an additional manufacturing site for the Jcovden COVID-19 vaccine from Janssen Pharma of the Johnson & Johnson.

CorbeVax News

December 23, 2022 - Local media in India reported a study conducted by AIG Hospitals and published by MDPI indicates a Corbevax booster in individuals vaccinated with COVISHEILD delivered maximum protection against SARS-CoV-2 Omicron virus variants.

December 23, 2022 - Local media indicates vaccine supplies were very low.

December 7, 2022 - Union Minister for Science & Technology, Dr. Jitendra Singh, said that India would make significant investments in research and development to create a roadmap for vaccine development.

October 14, 2022 - India's Union Health Ministry reported that Corbevax is available as a precaution/booster dose for adults fully vaccinated with Covishield or Covaxin.

October 11, 2022 - The WHO reviewed data for the Biological E COV-2 COVID-19 vaccine Corbevax™.

September 30, 2022 - The Houston Chronicle reported: A vaccine (IndoVac) developed by Dr. Peter Hotez had been approved for use in Indonesia.

August 20, 2022 - The Hindu's R. Prasad wrote: Due to faulty clinical trial design, the superiority of Corbevax heterologous booster over homologous boosters is not known.

August 16, 2022 - Union Health Minister Mansukh Mandaviya advised Indian states to widely publicize the availability of heterologous precaution Corbevax vaccines.

August 10, 2022 - PTI reported that “Corbevax will be considered as a precaution dose after completion of six months or 26 weeks from the date of administration of the second dose of either Covaxin or Covishield vaccines for those aged above 18 years, enabling the use of Corbevax as a heterologous COVID-19 vaccine for precaution dose administration in this age group,” the sources said.

August 9, 2022 - Fast Company published: Meet the scientists who created the first open-source COVID-19 vaccine.

August 4, 2022 - Peter Hotez, MD, Ph.D., discusses his coronavirus vaccine, CorbeVax, with AMA Chief Experience Officer Todd Unger.

August 2, 2022 - PTI reported the COVID-19 Working Group of the National Technical Advisory Group on Immunisation recommended allowing Biological E's Corbevax as a precaution 'booster' dose for adults fully vaccinated with either Covishield or Covaxin.

July 21, 2022 - USNews published: Dr. Peter Hotez: ‘Vaccine Diplomacy’ Is Essential to Conquer COVID.

July 8, 2022 - India's Standing Technical Sub-Committee of NTAGI recommended the use of the Corbevax vaccine for adolescents aged between 5-12 years.

July 1, 2022 - Local media reported that in Prune, India, Pune: about 37% of adolescents in the 12-14 age bracket had been vaccinated since mid-March 2022.

June 15, 2022 - The media reported the National Technical Advisory Group on Immunisation would review data on the Corbevax vaccines for the 6-12 age group and also deliberate on reducing the gap between the second and precaution doses.

June 4, 2022 - Biological E. Limited announced that the DCGI had approved Corbevax as a heterologous COVID-19 booster dose to adults and above after six months of administration of primary vaccination (two doses) of Covaxin or Covishield vaccines for restricted use in emergencies.

May 28, 2022 - COVID-19 vaccination of children in the post-Omicron era: An Indian perspective.

May 20, 2022 - Local media in India reported Biological E' Corbevax vaccines are being used to inoculate adolescents (12-14). Though the authorities launched campaigns to urge people to vaccinate their children during vacation and arranged facilities for this, most have declined to be immunized.

May 11, 2022 - Local media in India reported Biological E had submitted an application to India's drug regulator seeking authorization for Corbevax as a booster dose in adults fully vaccinated with Covishield or Covaxin.

May 4, 2022 - The media reported India's National Technical Advisory Group on Immunisation meeting to discuss vaccination protocols for 5-12-year-old children remained inconclusive.

May 4, 2022 - The India Ministry of Health and Family Welfare published updated results from its extensive COVID-19 vaccination program, including the CobeVax vaccine.

April 30, 2022 - DH media reported: Corbevax vs. Covovax; which one to choose?

April 29, 2022 -  PTI reported the Indian government plans to expedite the recognition process of Corbevax by other countries while its manufacturer Biological E pursues the WHO emergency use listing.

April 22, 2022 - India's drug authority recommended granting EAU to Corbevax vaccine for children (five to 11 years) with certain conditions.

April 14, 2022 - Local media reported India's DCGI's subject expert committee requested additional vaccine efficacy disclosures.

April 4, 2022 - Biological E. Limited announced that it had been selected as a recipient of mRNA technology from the World Health Organisation technology transfer hub. Established to address the COVID-19 emergency, the mRNA technology transfer hub has the potential to expand manufacturing capacity for other products, including treatments, and target other priorities.

April 1, 2022 - Corbevax vaccinations are available for adolescents in India.

March 28, 2022 - Bloomberg reported Corbevax had been approved for use in Botswana.

March 22, 2022 - The All India People's Science Network raised serious concerns over CorbeVax's approval, deployment, and decision-making processes. 

March 21, 2022 - The Times of India reported CoWIN data indicates that about 86,000 adolescents (12-14) in Maharashtra received the first dose of the 2-dose Corbevax vaccine within five days of launch.

March 17, 2022 - Local media reported the Centre extended vaccination for children between 12 and 14, allowing them to receive the Corbevax vaccine.

March 16, 2022 - Ms. Mahima Datla, Managing Director, Biological E. Limited, said, "As the entire country awaits the new phase of immunization drive for the 12 to 15 years, we at Biological E. Limited are privileged to support the Indian Government in this valiant exercise through our CORBEVAX vaccine. We are grateful to our Prime Minister, Shri Narendra Modi, for allowing us to join the fight against the deadly coronavirus."

March 15, 2022 - Local media reported the Centre released COVID-19 vaccination guidelines for children (12-14 years) that begin from March 16th, confirming that two doses of the Corbevax vaccine, 28 days apart, would be used for this age group. Additionally, Jayaprakash Muliyil, a National Technical Advisory Group on Immunisation (NTAGI) member, told The Wire Science on March 14th, "NTAGI has not recommended it. I don't know which other body has done it."

March 9, 2022 - Biological E has applied for a EUA for its Corbevax vaccine for the 5-12 year age group, according to a news report by ANI.

March 2, 2022 - The Wire Science reported that the Centre didn't wait for NTAGI's nod before it placed an order for five crore Corbevax doses from Biological E. 

February 21, 2022 - Biological E. Limited issued a press statement: Ms. Mahima Datla, Managing Director, Biological E. Limited, said, "We are pleased with this significant development, which helps extend the reach of our vaccine to the age group of 12 to 18 years in our country (India).... "We thank all the participants in the clinical trials, Biotechnology Industry Research Assistance Council and Department of Biotechnology, Govt of India, Translational Health Science and Technology Institute, and the principal investigators and clinical site staff who have extended their support during the last several months."

February 17, 2022 - Local media reported the Centre is likely to use five crore doses of Biological E's Corbevax vaccine for adolescents in early 2022.

February 14, 2022 - India's Drugs Controller General granted the restricted emergency use authorization to Biological E's COVID-19 vaccine Corbevax for adolescents 12 to 18 years.

February 3, 2022  - Local media reported the National Technical Advisory Group on Immunisation in India is likely to review the data for the usage of Corbevax among children.

January 24, 2022 - The Alliance for Science published: How does the CORBEVAX vaccine work?

January 19, 2022 - News18 in India reported a limited phase 3 clinical study evaluating the CorbeVax vaccine's effectiveness as a booster (3rd) dose following two doses of Covaxin.

January 17, 2022 - A vaccine called CORBEVAX can be manufactured cheaply in low-income countries without the complications of licensing or patents. "We want to help the world," says Dr. Maria Elena Bottazzi, who worked to develop the vaccine. "We think it's a gamechanger."

January 5, 2022 - Media in India reported, 'According to Dr. Hotez, traditional method "protein subunit vaccines" and "live inactivated vaccines" are cheaper and simpler to produce at the scale for low and middle-income countries.'

January 3, 3022 - A commentary published by the journal Nature, John N Nkengasong, director of the Africa CDC, called for African countries to increase investment in health and ultimately reconfigure their public health approach towards one of self-reliance. 

December 28, 2021 - Biological E. Limited announced that its CORBEVAX vaccine received approval from the Drugs Controller General of India. Biological E. Limited plans to complete production at a rate of 75 million doses per month, anticipating 100+ million doses per month from February 2022. 

June 10, 2021 - The India Express reported: that India has placed an advance order to block 300 million doses of a new Covid-19 vaccine, Corbevax, from Hyderabad-based company Biological E. What is this vaccine, and why is it important for India?

June 4, 2021 - Local media reported the Indian government confirmed it would make an advance payment of Rs 1,500 crore to Biological E to reserve 30 crore doses of its under-development Covid-19 vaccine.

April 24, 2021 - Biological E. Limited announced that it had completed the Phase I/II clinical trial of its COVID-19 subunit vaccine candidate in India and received the approval to start the Phase III clinical trial from the Central Drugs Standard Control Organization - Subject Expert Committee.

December 29, 2020 - CEPI, the Coalition for Epidemic Preparedness Innovations and Biological E Limited, India, announced a collaboration to advance the development and manufacture of Bio E's COVID-19 subunit vaccine candidate. CEPI will initially contribute up to $5m toward the cost of scaling up the process for manufacturing the vaccine and will potentially explore providing additional funding to Bio E to produce 100 million doses in 2021. The candidate has also received seed funding from the Department of Biotechnology, Government of India.

November 17, 2020 - Biological E. Ltd initiates Phase 1 and 2 clinical trials in India. Biological E's vaccine candidate includes an antigen licensed from BCM Ventures and an advanced adjuvant CpG 1018 from Dynavax. "This vaccine represents an urgent biotechnology innovation for ensuring health equity and combating the COVID-19 pandemic," said Dr. Peter Hotez, professor and dean of the National School of Tropical Medicine at Baylor and co-director of Texas Children's Hospital Center for Vaccine Development.

CorbeVax COVID-19 Vaccine Clinical Trials

A phase 3 study evaluates the immune response and safety of the single-dose Corbevax vaccine for booster protection, according to the Drugs Controller General of India accessed by News18.com. A total of 360 subjects will be enrolled in one of the two groups for safety and immunogenicity assessment. "A total of 180 volunteers who were primed 6- 8 months ago with Covishield vaccine will be enrolled into group-I, and volunteers who were primed 6-8 months ago with Covaxin will be enrolled into group-II," the protocol said. As per the document, all participants will receive a 0.5 ml single dose of Corbevax intramuscularly. In addition, the participants will be followed up for 28 days for any safety issues.

CorbeVax has completed two Phase III clinical trials involving more than 3,000 subjects between the ages of 18 and 80 at 33 study sites across India. The vaccine was found to be safe, well-tolerated, and immunogenic.

• In the pivotal Phase III study conducted with an endpoint of immunogenic superiority, CorbeVax demonstrated a superior immune response than the COVISHIELD vaccine when assessed for Neutralizing Antibody (nAb) Geometric Mean Titers (GMT) against the Ancestral-Wuhan strain and the globally dominant Delta variant. In addition, CorbeVax vaccination also generated a significant Th1 skewed cellular immune response.
• CorbeVax nAb GMT against Ancestral-Wuhan strain indicates vaccine effectiveness of >90% for prevention of symptomatic infections based on the Correlates of Protection assessment performed during Moderna and Astra-Zeneca vaccine Phase III studies.
• CorbeVax nAb GMT against the Delta strain indicates vaccine effectiveness of >80 percent for preventing symptomatic infections based on published studies.
• While none of the subjects who took CorbeVax or COVISHIELD had serious adverse events, CorbeVax had 50 percent fewer adverse events than COVISHIELD.

A previous Phase I/II clinical trial evaluated the safety and immunogenicity of the vaccine candidate in about 360 healthy subjects aged 18-65 years. The schedule consisted of two doses for each participant, administered via intramuscular injection, 28 days apart. Bio E's novel Covid-19 vaccine was safe, well-tolerated, and immunogenic.

Findings

Findings published in The Lancet showed a low incidence of adverse events, while antibodies persisted for 12 months after the second dose of the vaccine.