BENGALURU: The recent approval by the Drug Controller General of India for a heterologous prime boost study, commonly called ‘mixing of vaccine’ study, has drawn appreciation by experts. After a study on a small group of 18 subjects by ICMR, for the first time in India, over 300 people will be part of a study by CMC Vellore.
“We know that a number of vaccines based on different platforms — MrNA, inactivated viral, viral vector vaccine and protein based — are also coming. There is wide interest among researchers to understand how this works. Outside India, such studies have already found that the antibodies generated are far higher than the same vaccine given in two shots,” said Dr Chandrakant Lahariya, renowned epidemiologist and policy expert.
The study by CMC Vellore will investigate important questions like safety, immunogenicity and reactivity on mixing the two most available vaccines in India— Covishield and Covaxin. These two vaccines, while aiming at the spike protein, are made differently.
Covishield is made of genes of the spike protein wrapped in a weakened adenovirus, that transports the genes into the body’s cells, where its machinery makes more such spike protein, invoking an immune response. Covaxin is an inactivated SARS-CoV2 virus— a more traditional method of manufacture— that exposes a non-replicating part of the virus to the body’s immune system. Current evidence suggests that both successfully elicit significant antibody levels but are affected differently by virus variants.
Dr T Jacob John, epidemiologist and former professor at CMC Vellore, says all vaccines require a booster dose, and two doses are not enough. Mixing of vaccines is like an interim stop-gap arrangement. Explaining how two doses of vaccine work, he said, “All vaccines have different forms of spike protein. Once the immune system is stimulated with one particular spike protein configuration, and a different one is given, the immune system will broaden its response to cover a range of variations and also provide higher antibody response. The body takes it as a threat and responds with high antibody response.”
However, he insisted that this mixing and matching is not the solution to India’s vaccine issue. “It’s a shame that India has been able to vaccinate only 8.9 per cent of its population, even after seven months of emergency use approval,” he said.Experts feel that antibody response may be even better if the first two doses are of the same vaccine, and the booster dose is a different one.
Participants in the trial study by CMC Vellore would be a mix of health workers and people in the community. Many other countries have experimented with different vaccines — the Com-Cov clinical trial in the United Kingdom, which mixed Pfizer with AstraZeneca, and Spanish CombivacS trial which again tested the same vaccine combination. Provinces in Canada have allowed vaccines to be mixed and matched. While the effectiveness is not proven, experts said safety was unlikely to be a major concern. A study in Russia showed that mixing Sputnik V, available in India, with AstraZeneca had no serious side-effects.