Covid-19 booster dose: ‘Precautionary’ doses for vulnerable groups have begun, using the same vaccine the beneficiaries were previously given. What is the rationale behind this, and the arguments for and against mixing vaccines?
On Monday, the government began administering an additional “precautionary” dose of the Covid-19 vaccine to vulnerable groups, including those over age 60 and with comorbidities, as well as healthcare and frontline workers. The two main vaccines in India’s immunisation programme, Covishield and Covaxin, are given in two doses, so the “precautionary” or “booster” dose is the third one for those eligible.
Over 63 crore Indians have received both doses of their vaccine until Sunday, out of nearly 150 crore doses administered overall.
For those eligible for the booster, the Centre has not allowed mixing of vaccines as of now: If someone has received two doses of Covishield, she will be given the same vaccine for the third shot, and so also for Covaxin. Once more data is available, a heterologous approach (using a different vaccine for the third jab) will be taken later on, the Centre has said.
What purpose does a boosters serve?
The immunity provided by a regular course of vaccines is known to wane over time. Various studies in India and elsewhere have reported a decline in antibodies of vaccinated people, recorded at various points of time after the last dose. This decline happens not only with antibodies, but even memory T-cells.
A booster dose is given so that people can maintain their level of immunity for longer. In the past, boosters were recommended for smallpox prevention every three to five years. Tetanus toxoid boosters are also recommended today for adults and pregnant women after childhood vaccination.
Regulators in some countries, such as the United States’ Food and Drug Administration (FDA) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHDA), have looked at booster dose data and given approvals based on that.
In India, a recent study found that six months after the second Covaxin dose, a booster using the vaccine as a booster dose led to neutralising T cell and B cell responses. This suggests good immune memory responses and long-term protection from severe disease, manufacturer Bharat Biotech said in a statement.
Why has the Centre chosen to use the same vaccine for all shots?
There are regulatory and clinical aspects. From a regulatory and legal perspective, according to Dr Gagandeep Kang, one of India’s best-known vaccinologists, it makes sense to give the same vaccine as the previous two doses until there is sufficient data to make a policy decision on using a different vaccine as the third dose.
“These vaccines are under emergency use authorization (EUA) which means that they are not fully licensed. For instance, in the national programme on immunisation, we have off-label recommendation for the rotavirus vaccine. The programme itself says it can give the first dose up to 12 months, whereas the manufacturer says can give up to eight months. For the inactivated polio vaccine… the licence is for a full dose given intramuscularly. What this means is that off-label use for products that are licensed is one thing, but the same for ones that are under EUA is another issue,” Dr Kang said.
“We also have to consider the issue of indemnity. What if something goes wrong when you use another vaccine: then who is responsible?” she said.
From the clinical standpoint, leading virologist Dr V Ravi noted that the fundamental attribute of the immune system is memory. “If you shoot with the same vaccine one will boost the memory. Boosting with a homologous vaccine [the same one given earlier] will also fetch a good response,” Dr Ravi said.
Immunologist Dr Vineeta Bal said many traditional vaccines are used as a second or third dose as the primary vaccination regime followed by a booster of the same a few months or years later. For instance, tetanus toxoid is part of the childhood vaccination programme and is recommended at a later age too, including pregnant women.
What have studies found on the mixing of Covid-19 vaccines?
In India, there is no clear data yet on mixing the two vaccines that make up the bulk of the doses being administered: Covishield and Covaxin.
Efforts being taken up to generate and analyse data. A recent pilot study by the Asian Institute of Gastroenterology (AIG) examined the safety profile of mixing Covishield and Covaxin and also checked antibody response by comparing small homologous and heterologous vaccine groups. It found that mixing vaccines was safe.
Dr D Nageshwar Reddy, Chairman, AIG Hospitals, has said the most important finding of the study was that antibodies neutralising the coronavirus spike protein were significantly in the mixed-vaccine groups than in the same-vaccine groups. “We have communicated details of the study to ICMR (Indian Council of Medical Research),” Dr Reddy has said.
Considering that there would be a demand for booster doses, the Christian Medical College in Vellore, too, has taken up a study on the feasibility of the mixing of Covid-19 vaccine doses. The results are likely to be out by February this year.
Though heterologous boosting appears to be safe, data on long-term safety is yet to be generated.
But why look at mixing vaccines as an option?
According to the World Health Organization, homologous vaccine schedules are standard practice based on substantial safety, immunogenicity and efficacy data. The European Centre for Disease Prevention and Control (ECDC) has said that a heterologous booster vaccine strategy may be considered as an alternative strategy to improve vaccine protection and provide flexibility in vaccine supply and availability issues.
Dr Sanjay Pujari, member of the ICMR national Covid-19 task force, referred to immunogenicity studies that have demonstrated higher immune responses with heterologous schedules. However they are limited by short-term data. “Understanding of how immunogenicity data translates into vaccine effectiveness is still evolving and immune correlates for absolute protection are still unclear,” Dr Pujari said.
Dr Bal said noted, however, that in general, in many contexts (including Covid-19), a mix-and-match strategy has been visualised or used. For example, for DNA vaccines, protein-based vaccines were considered in prime-boost situations.
Can there be issues over supply?
Experts have stressed the importance of achieving a right balance between effectiveness and safety concerns and the availability of vaccine platforms and supplies. “Apart from the absence of Indian data in the public domain on how mix-and-match vaccination would benefit, there could be supply chain, vaccine availability issues,” Dr Bal said.
Of the nearly 150 crore vaccine doses given until Sunday, over 130 crore are of Covishield (5 in every 6) and over 19 crore are of Covaxin. Experts noted that since Covaxin is the only one in use for under-18 vaccination, there could be a possibility of a shortage of the vaccine for heterologous boosting of the Indian adult population.