The Drug Controller General of India (DCGI) has approved a clinical trial, to be conducted by the Christian Medical College, Vellore, to evaluate if a mixed vaccine combination can work as opposed to the current policy of both doses being the same vaccine.
India has administered 45.6 crore vaccine doses so far of which nearly 88% are Covishield. With limited supplies of Covaxin, a mixed dose regime may help cover a supply shortfall.
“After detailed deliberation, the committee recommended for grant of permission for conduct of the Phase IV clinical trial,” said the minutes of the meeting that were made public on Friday, though details of the trial were not.
A Phase 4 trial is intended to study the effects of treatment or medical product once it has been licensed for public use. In this case, because both Covaxin and Covishield have been approved under emergency use authorisation, the trial is expected to investigate a range of questions, including whether combining vaccines elicits a different level of antibodies to the virus, whether a combination may be more effective against variants and if such a regime would be safe.
“Safety, immunogenicity and reactivity are among the main questions that we will be investigating,” said Dr. Jacob John, of the Christian Medical College, Vellore and one of the investigators of the trial. He said that those participating in the trial would be a mix of health workers and people in the community and said that 500-600 volunteers would be potentially available.
Many other countries have experimented with having different vaccines in trial mode most, prominently the Com-Cov clinical trial in the United Kingdom, which mixed Pfizer with AstraZeneca, and the Spanish CombivacS trial which again tested the same vaccine combination. Provinces in Canada have allowed vaccines to be mixed and matched. While the effectiveness of these combinations is not proven, experts said safety was unlikely to be a major concern, though it would take a very large pool of volunteers to establish it either way.
“There have been different vaccines for whooping cough,” said T. Jacob John, epidemiologist and formerly with the CMC Vellore. “ In the case of the coronavirus vaccines, they are all aimed at the spike protein so it's unlikely safety would be a major concern as these aspects have been evaluated earlier. However when mixing vaccines, it’s the specific research questions being asked that matter.”
On Friday, the makers of the Sputnik V vaccine, also available in limited quantities in India, reported that a trial on 50 volunteers in Azerbaijan, who received the Russian vaccine and AstraZeneca had proven to have “a high safety profile” and no serious adverse events.
Covaxin and Covishield, while aimed at the spike protein, are made differently. Covishield is genes of the spike protein wrapped in a weakened adenovirus, that transports these genes into the body’s cells where it’s machinery makes more such spike protein, invoking an immune response. Covaxin is an inactivated sSARS-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.