Need to probe safety and efficacy of mixing Covid shots that use different platforms, in the light of possible immunity blow to efficacy of the second dose of the same vax
On June 22, German Chancellor Angela Merkel received her second shot of the Covid vaccine. She opted to receive Moderna‘s mRNA vaccine for this shot, though she had received the AstraZeneca vaccine as the first shot. Though no explanation was publicly offered, her background as a scientist makes her an astute tracker of advancing research in vaccine efficacy.
The same day, Italian premier Mario Draghi too changed vaccines for his second shot. While he had earlier received the AstraZeneca vaccine, he chose to receive the Pfizer-BioNTech vaccine on the second occasion. He said he had been told that his first dose had given a “low antibody response.”
Whether mixing Covid-19 vaccines enhances safety or reduces safety is a question that has been debated for sometime. Mixing of vaccines using the same platform began when the Pfizer and Moderna vaccines were used interchangeably in USA, depending on availability. No adverse effects were noted, in this recourse to expediency. The Russian virus-vector vaccine (Sputnik-V) too uses different human adenoviruses in the two shots, to carry the spike protein code into human cells. That vaccine was deliberately designed and trialled that way.
However, it is when vaccines using two different platforms are mixed that more probing questions arise about the science behind it. Clinical trials have not as yet provided data on the efficacy and safety of such combinations, though some have just begun. At present, we have to go by immunogenicity studies, supported by ‘real world’ data as it emerges in countries which have already commenced that practice.
Several European countries have tried out mixed vaccines. The practice was triggered by turns and twists in regulatory approvals for the AstraZeneca vaccine, both by national regulators and the European Medicines Agency. Several countries did not initially approve the vaccine for use in the elderly, as the original international trial of the vaccine did not include adequate number of such persons. It was permitted only for younger ages. Later, regulators reversed the stand, when disconcerting reports emerged of clotting risks among young persons, especially women. The recommendation was amended, to avoid the vaccine in the young but use in the elderly! As this U-turn was implemented, other vaccines came to be used for the second shots.
Interruption of anticipated AstraZeneca supplies from India also created a need for European countries to mix vaccines created on different platforms. Those attempts have now yielded evidence that the immune response is markedly enhanced when a first shot of AstraZeneca is followed by a second shot with an mRNA vaccine. This is especially important for the elderly, in whom the immune response tends to be weaker than in the young. Merkel and Draghi have endorsed that emerging science with their arms.
One of the reasons why the second shot of the AstraZeneca vaccine may have relatively low immune response is because of the common virus vector employed in both doses. The chimpanzee adenovirus which carries the spike protein code into human cells is the same in both shots. While that courier virus is innocuous, it may still excite an immune response when it is delivered in the first shot. That may prevent the courier virus from effectively delivering the spike protein code after the second shot. How can the postman deliver the package when the home owner’s guard dog drives him away from the gate? The Russians were smart in using two different vector viruses (human adenoviruses 5 and 26) in their shots. A trial, mixing the AstraZeneca and the Russian vaccines, is on the cards.
What about India? We have a younger population than Europe. The overall immune response to the AstraZeneca vaccine’s Indian version may still be robust among the younger sections of the population. Concerns will still remain for the elderly. Should they be prioritised for the Moderna or Pfizer vaccines when they arrive? Will new protein sub-unit vaccines serve to boost the immune response? Our scientific and regulatory agencies will have to guide us.
Beyond intrinsic ability to stoke a strong immune response, there are questions regarding the ability of vaccines to overcome the challenge of current and future variants. The mRNA vaccines produce a strong enough immune response to overcome the currently circulating variants, despite some reduction in efficacy compared to the wild virus or its Alpha variant. However, evidence related to the extent of AstraZeneca vaccine’s efficacy against the Delta variant is conflicting, posing uncertainty. Under these circumstances, those with access to mRNA vaccines are opting for them as the choice for the second shot. No wonder the Indian elite anxiously await their arrival, to toast with the Merkel Mix cocktail!
Fortunately, the recently released results of the completed Covaxin trial, give us comfort. The inactivated virus, which forms the platform, offers several antigens besides the spike protein. The broadband immune response that is evoked against multiple antigens can overcome variants which arm themselves with shape altering spike-protein mutations. Indeed, the trial results not only show high levels of overall efficacy against Covid-19, but have also provided evidence of protection against the Delta variant. We may not need an mRNA vaccine to provide added protection.
So, it appears that mRNA vaccines and multi-antigen vaccines help us land safely in the zone of protective immunity even when threatened by variants, just as CAT-3 instrument landing systems help planes to alight safely on the intended runway in the dense fog of Delhi winters.
The author, a cardiologist and epidemiologist, is president, Public Health Foundation of India (PHFI)
Views are personal