‘Our results have shown that two doses of Covaxin provide strong immunity’, says the Bharat Biotech CMD.
New Delhi: The Indian government has recently allowed children between the age group of 12 to 18 years to be inoculated with the Indian manufactured Covaxin after studies showed it to be safe to be used on children. Dr Krishna Ella, Chief Managing Director of Bharat Biotech, the company manufacturing Covaxin, in an interview to The Sunday Guardian said that the vaccine has shown good immunogenicity amongst children between 2 to 18 years of age and also spoke about the nasal vaccine that his company is working on. Dr Ella spoke about the company’s vision to reach 1 billion doses annually. Excerpts.
Q: How far is Covaxin effective against Omicron and all other variants of Covid?
A: Covaxin, a virion-inactivated vaccine covers the entire virus and we believe it can work against this highly mutated new variant too. Covaxin had demonstrated 77.8% effectiveness against symptomatic Covid-19 and 65.2% protection against the Delta variant.
Indian Council of Medical Research’s (ICMR’s) recent study established that Covaxin could neutralise the Delta, Delta Plus, and the B.1.617.3 variants. Another study published on Thursday in “Clinical Infectious Diseases”, a peer-reviewed journal, titled “Neutralisation of variant under investigation B.1.617 with sera of BBV152 vaccine” also concluded that inoculation with Covaxin produced neutralising titres against all key emerging variants tested, including BI617 and B117—first identified in India and the UK, respectively
In our recent study, a third booster shot of Covaxin, administered six months after the second dose, induced both memory B and T cells and led to a pronounced increase in T-cell responses, indicating the inactivated virus vaccine may be able to confer long-term protective efficacy against severe SARS-CoV-2, a study by ICMR’s National Institute of Virology, Pune, has shown.
In addition to controlling infections, the adaptive immune system creates immunological memory, such as memory B and T cells, to enable long-term protection against a virus.
In a recent study by AIIMS Delhiresearchers on healthcare workers, two doses of Covaxin were 86% effective in preventing symptomatic Covid-19 reinfections among healthcare workers in India during the second wave. The research also showed that despite the surge of cases in April last year, and the high transmissibility of the Delta variant, healthcare workers who had received two doses of Covaxin were at lower risk of reinfection.
Bharat Biotech has evaluated Covaxin in adults, children (2-18 years), for 2-dose primary schedule and booster schedule. Covaxin has demonstrated safety, immunogenicity, efficacy and effectiveness. The same vaccine dosage can be administered to adults and children alike, making it a universal vaccine.
Q: Do you feel that children may need precautionary doses too after receiving a Covaxin jab?
A:It is too early to remark on this, as we are in the phase of administering the vaccine to children, and only a follow-up study and analysis after 2 doses are given, will help us understand whether precautionary doses can be considered. This decision will be made by the regulatory body.
However, our results have shown the two doses of Covaxin provide strong immunity. Covaxin is one of the first Covid-19 vaccines in the world to generate data in the 2-18-year age group. Phase II and III, open-label, multi-centre study was conducted to evaluate the safety, reactogenicity, and immunogenicity of the whole-virion inactivated SARS-CoV-2 vaccine (Covaxin) in healthy children and adolescents in the 2-18 age group.
Whole-virion inactivated SARS-CoV-2 vaccine (BBV152) has proven to be safe, well-tolerated, and immunogenic in paediatric subjects in phases II and III study. Neutralizing antibodies in children is on an average 1.7 times higher than in adults.
Q: What are your views on heterologous Covid vaccine dose? Which one do you feel will work better against the Covid variants—homologous doses or heterologous doses?
A: In our booster dose study announced by us recently, we have been able to establish “promising” results. The phase 2, double-blind, randomised controlled Covaxin trial demonstrated long-term safety with no serious adverse events. The booster shot was given six months after the second Covaxin dose. It was demonstrated that Covaxin generated both humoral and cell mediated immune responses that persisted at 6 months.
The analysis showed, six months after a two-dose BBV152 vaccination series cell-mediated immunity and neutralising antibodies to both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, and Delta plus) persisted above baseline, although the magnitude of the responses had declined.
Furthermore, neutralising antibodies against homologous and heterologous SARS-CoV-2 variants increased 19- to 265-fold after a third vaccination. Booster BBV152 vaccination is safe and may be necessary to ensure persistent immunity to prevent breakthrough infections.
Recently there have been published studies on heterologous booster doses, where the results were promising. These combinations of vaccines have to be further studied, final approvals for heterologous booster doses have to be given by CDSCO.
Q: Since Bharat Biotech is working on the manufacturing of nasal vaccines, what is the current status of the vaccine so far? What trial stage is it in and when is it likely to be available in the market?
A: Only recently, we have received a nod for phase 3 trials for the intranasal vaccine and a study to ascertain its use as a booster dose. The subject expert committee (SEC) under India’s drug regulator has recommended that Bharat Biotech can conduct phase-3 trials on its intranasal vaccine.
Bharat Biotech aims to conduct clinical trials on 5,000 healthy people. The company has proposed to use its intranasal vaccine as a heterologous booster dose in individuals who are already vaccinated: those who have received two doses of either Bharat Biotech’s Covaxin or the other vaccine.
The interval between the second dose and the intranasal booster dose will be six months.
Our scientific hypothesis behind developing the Intra-nasal vaccine is to tackle three important things—that is to enable our vaccine to have a broad immune response neutralizing IgG, Imucosal IgA, and T cell. We believe our nasal vaccine will provide all three.
Furthermore, an injectable vaccine only provides IgG and T-cell responses. IgA provides a broad spectrum of immunity, and it protects all the nasal areas—Imucosal. That is where the virus starts attacking and if you have an immune response right there and the gate of entry is blocked, with the intent to prevent infections and reduce transmission.
Based on successful completion of the trials and positive results, we will be submitting the final data to the regulator, upon receiving the usage approval we will roll out the vaccine.
Q: Will the nasal vaccine be available for children? Can nasal vaccines be administered without medical guidance at home?
A: A nasal vaccine may be a good choice across age groups because it will be single-dose and easy to administer. But it has to be evaluated in children prior to administration. Based on current knowledge and guidelines for vaccinations, nasal vaccines will be administered in clinical settings only under the guidance of medical professionals.
Q: Strictly speaking of numbers, why has Covaxin been left far behind Covishield in terms of vaccination in India?
A: Inactivated vaccines are one of the toughest vaccines to produce in the world. The number of steps to manufacture a vaccine with an inactivated virus is much more than ones conducted for adenovirus vector-based vaccines. Covaxin falls in the former category and Covishield in the latter. Covaxin requires biosafety level 3 manufacturing facilities, which were not readily available.
The whole inactivated virus vaccine produced in Vero cells is a very complex manufacturing process, involving several steps with a high degree of complexity. The processes include adherent cell culture process, virus inactivation, multiple purification steps, filling of sterile-filtered formulated bulk into vials in aseptic condition.
The timeline for manufacturing, testing, and release for a batch of Covaxin is around 120 days. Covaxin is developed using Whole-Virion Inactivated Vero Cell-derived platform technology, and the manufacturing, testing, release, and distribution of this vaccine is a complex and multi-factorial process with hundreds of steps, requiring a diverse pool of human resources.
Despite these challenges, in a short period we were able to upgrade, repurpose our facilities both existing and our new production lines in Hyderabad, Pune, Bangalore, and Ankleshwar achieving up to 80 million doses per annum now, which will touch 1 billion doses. Currently all companies in India have a combined capacity of 40 million doses / year for Rabies vaccines, which is also an inactivated vaccine using a similar manufacturing platform as Covaxin.
The large-scale capacity expansion for Covaxin was started during March 2021, when phase 3 clinical trial efficacy results were available. Bharat Biotech was not funded nor given a contract to manufacture Covaxin at risk, prior to the availability of phase 3 efficacy data. If Bharat Biotech was provided funding to manufacture doses at risk during Q3 2020, the manufacturing scale up could have been executed earlier and large quantities of doses could have been made available starting from Q2 2021.
Q: How many Covaxin doses is the company planning to roll out in the coming days? What steps are being taken to meet the increasing demand as children are now being inoculated with this vaccine?
A: This month we have delivered 5.8 crore doses to the Government, in the coming months we hope to deliver between 7-8 crores of doses. Our roll-out is being conducted in a step-by-step process in each of our facilities. We will be achieving our 1 billion doses per annum target soon; we have attained a capacity to produce up to 80 million doses of Covaxin per month.
Capacity expansion in vaccine manufacturing is a long and tedious process, requiring investments of several millions of rupees and several years. Bharat Biotech was able to expand Covaxin manufacturing capacity in a short timeline, mainly due to the availability of new specially designed BSL-3 facilities, first of its kind for manufacturing in India that have been repurposed and pre-existing expertise and know-how to manufacture, test, and release highly purified inactivated viral vaccines.
We have also scaled up our manufacturing in a stepwise manner across multiple, specially designed Bio-Safety Level-3 production facilities in Hyderabad in Telangana, Malur in Karnataka, and Ankleshwar in Gujarat and Pune, Maharashtra, with our current production ability to produce 70-80 million doses per annum, we are well on track and on target, to accomplish an annualized 1.0 billion doses of Covaxin.
Manufacturing partnerships are being explored with our partners in other countries, who have prior expertise with commercial-scale manufacture of inactivated viral vaccines under biosafety containment.
To further increase capacities, Bharat Biotech has entered into technology transfer partnerships with four companies in India. One company has commenced manufacturing and is supplying drug substances to Bharat Biotech.