Covishield and Covaxin mixing is safe and has better immunogenicity. Many discoveries in medicine have been the result of serendipity or by chance... the most iconic of them being the discovery of penicillin.

A new ICMR study has shown that mixing of Covishield and Covaxin is not only safe, but also elicits better immunity against COVID-19. Aptly titled “Serendipitous Covid-19 vaccine-mix in Uttar Pradesh, India: safety and immunogenicity assessment of a heterologous regime”, this study was a result of inadvertent administration of Covaxin as the second dose to 20 individuals who had received Covishield as the first dose. Covishield is an adenovirus vector vaccine, while Covaxin is an inactivated whole virus vaccine.Though administered by chance, an opportunity presented itself serendipitously to study the benefits of combining two different COVID-19 vaccines, a subject which is already being discussed and has garnered much global attention. In this trial, the safety and immunogenicity of a heterologous vaccine regimen was compared to that seen in 40 individuals each who were given either Covishield or Covaxin. The study was carried out from May to June 2021 and has been posted August 7, 2021 as a preprint in medRxiv.Results demonstrated that overall the combination of the adenovirus vector platform-based vaccine (AstraZeneca), followed by the inactivated whole virus vaccine (Covaxin) was not only safe but also produced better immunogenicity compared to the homologous vaccine groups using the same vaccines. The neutralizing antibody titers were found to be significantly higher and efficient in neutralizing the variants of concern (Alpha, Beta and Delta) in the heterologous vaccine group vs the homologous vaccine groups. The humoral immune response in the heterologous group (IgG titers for S1-RBD, N protein and inactivated SARS-CoV-2 antigen) was also significantly higher in comparison to the homologous groups. There were no major differences in the side effects between the three vaccine groups; the most commonly reported systemic AEFI were pyrexia and malaise, while pain at injection site was the most common local AEFI. No major systemic AEFIs were reported.Although a larger trial is needed to corroborate these findings, they do have important public health implications considering the shortage of COVID-19 vaccines in many parts of the world (including in India), the varying efficacies of different vaccines and the still prevailing vaccine hesitancy.AstraZeneca (as the initial dose) and Pfizer (as the follow up dose) vaccines have been mixed in the UK Com-COV trial and the Spanish CombivacS trial. Preliminary results have been encouraging with strong immune response against SARS CoV-2, though final results are awaited. The National Institutes of Health (NIH) have started a Phase 1/2 clinical trial to examine the safety and immunogenicity of mixed boosted regimens. Fully-vaccinated trial participants will receive booster doses of different COVID-19 vaccines and then be followed for one year to allow for the evaluation of safety and other post-vaccination side effects. The initial trial results are expected in late summer 2021.The first component of Sputnik V – Ad 26 (human adenovirus serotype 26) has been mixed with the Oxford Astrazeneca vaccine. Initial results show this combination to be safe.Covaxin and Covishield are the two major vaccines under the national Covid-19 vaccination program, which has now been supplemented by the emergency use approvals of Sputnik V, J&J and Moderna COVID-19 vaccines. India has the unique advantage of being able to test combinations of vaccines that have been developed using diverse platforms. As reported, the CDSCO (Central Drugs Standard Control Organisation) has recommended a trial of mixing Covishield and Covaxin with a larger group of 300 healthy volunteers. This trial will be conducted by Christian Medical College in Vellore.The Chief Scientist WHO had cautioned that “Individuals should not decide for themselves, public health agencies can, based on available data. Data from mix and match studies of different vaccines are awaited – immunogenicity and safety both need to be evaluated.”India currently does not recommend combining two different vaccines.

Will India switch to a “mix and match” vaccine policy? Time alone will have the answer to this research question in public health.