Covid-19 vaccine cocktail: The good, the bad, and the conflict

Covid-19 vaccine cocktail: The good, the bad, and the conflict Medical workers carry vaccines stored in a freezer from a depot during COVID-induced lockdown in Bengaluru, Thursday, May 27, 2021. (PTI Photo)

by Abhishek Shankar, Shubham Roy, Deepak Saini

With the shortage of COVID-19 vaccines affecting the rollout in different states, especially for the second dose, researchers are exploring the idea of mixing and matching the shots.

All COVID-19 vaccines approved, so far, are designed to teach the immune system to recognise and defend against the virus with a first dose, and then provide a second dose to boost the immune response. The prospect of mixing vaccines doses offers a chance to bolster vaccine rollouts and potentially boost the immunity provided, but there is paucity of evidence when it comes to COVID-19.

Three teachers posted at a vaccination centre in Maharashtra’s Jalna district were recently suspended for dereliction of duty after a probe revealed that a 72-year-old man was administered jabs of two different COVID-19 vaccines. He received a Covaxin shot followed by a Covishield dose.

NITI Aayog member (Health) VK Paul clarified on the unlikely possibility of significant adverse effects if the second dose is a different COVID-19 vaccine. At the same time, he called for more scrutiny and understanding before concluding that taking doses of two different vaccines can lead to stronger immunity.

When many European countries put a temporary hold on the AstraZeneca–Oxford vaccine, called Covishield in India, following reports of blood clots, the idea of mixing the shot with other vaccine brands was encouraged. Health agencies in France and Germany urged people who had received the AstraZeneca shot, which uses adenovirus, to consider getting one of the mRNA vaccines when going for their second dose. Experts argued that mixing two different vaccines could actually do a better job of protecting against COVID-19.

This is not the first time that the concept of ‘cocktail’ vaccine has been proposed.

In 2017, researchers at the Moscow-based Gamaleya Research Institute of Epidemiology and Microbiology created an Ebola vaccine, which contained an adenovirus in the first dose, while the second shot used another virus called vesicular stomatitis virus.

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AstraZeneca’s adenovirus vaccine uses a weakened version of the common cold virus found in chimpanzees to present the spike protein to the immune system, while Pfizer’s mRNA-based vaccine delivers genetic instructions for making the spike protein and encourages human cells to produce it. It does make some simple sense that sparking more than one arm of the immune system could boost immunity on the whole.

In fact, the Gamaleya Research Institute and AstraZeneca have registered clinical trials on mixing a dose of AstraZeneca’s vaccine with Sputnik V developed by the former. Trials are underway in Russia and Azerbaijan. Norway is also awaiting the results of a clinical trial where vaccines were mixed.

A similar study is underway in the UK where the Oxford University is testing various combinations of the vaccines currently approved in Britain – Pfizer-BioNTech, AstraZeneca and Moderna. The trial, called Com-COV2, is also considering adding Novavax’s candidate to the mix once it receives approval.

The Com-COV2 study was launched in February by the Oxford University to probe immune responses when given a shot of AstraZeneca vaccine followed by the Pfizer jab, and vice-versa. The idea is to add flexibility in vaccine rollout to help deal with disruption in supply.

Preliminary findings from the study published in medical journal The Lancet say adults are more likely to report mild and moderate side effects when doses are mixed. One in 10 volunteers who were given two AstraZeneca jabs four weeks apart reported feeling feverish. But when they were given one AstraZeneca dose and one Pfizer shot, 34 per cent volunteers reported fever symptoms. Any adverse reactions were short-lived and there were no other safety concerns, initial findings showed. Among those who received the Pfizer dose before AstraZeneca shot, 41% reported fever as compared to 21% among those given two doses of Pfizer.

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The trial, which has recruited 830 volunteers aged over 50, is expected to publish its first full results this month. The trial was expanded in April to add 1,050 volunteers to test combinations of the Moderna and Novavax jabs.

Many Indians are now waiting for the second dose of vaccination amid limited supply which has been further hit by the second wave. Some even opted for a different second dose given the paucity.

Many more vaccine brands are likely to be available for use in India in the coming days with the government and health authorities giving emergency use approval. But with limited data on mixing of vaccines, it will be difficult to arrive at a sure-shot combination of doses for better efficacy and fewer side effects.

Another big question surrounding the mixing of vaccines is the gap between two doses. The four-week gap for those taking AstraZeneca’s Covishield shot has been extended from four weeks to 12-16 weeks in India, whereas the recommended gap for Bharat Biotech’s Covaxin is four weeks. Russia’s Sputnik V, which has been approved for emergency use, has recommended three weeks’ gap between two doses.

According to the US Centre for Disease Control and Prevention, people should wait no more than six weeks while taking Pfizer and Moderna doses.

Dr Abhishek Shankar is Assistant Professor in Department of Radiation Oncology at Lady Hardinge Medical College & SSK Hospital, Delhi. Dr Shubham Roy is a Fellow at Ummeed Child Development Center, Mumbai. Dr Deepak Saini is Project Officer at Cancer Control and Prevention Division of Indian Society of Clinical Oncology, Delhi. Views expressed are personal.

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