DNA Explainer: The science behind mix-and-match COVID-19 vaccines

CMC Vellore has got the nod to begin its research study on mixing of the Covaxin and Covishield vaccines doses. CMC proposal was earlier approved by an independent panel affiliated with drugs regulator.  

With the advent of very powerful variants like Delta, Delta Plus, Alpha experts around the world are studying whether a combination of two different vaccines can outperform two doses of the same vaccine.  

Recently, ICMR conducted a similar study where one dose of Covishield and one dose of Covaxin were mixed, and the results of the study found it to be safe and also found to provide better immunity.   

The two main vaccines used in India for the inoculation process are Covishield and Covaxin. Covishield is an adenovirus vector platform-based vaccine, while Covaxin is an inactivated whole virus vaccine.  

Experts however have cautioned that mixing of vaccines should not be randomly done but should be based on understanding multiple issues.  

ICMR study on vaccine mix  

This study was based on an observation of 18 villagers in Uttar Pradesh who were mistakenly administered Covaxin as the second dose in May this year, six weeks after they got Covishield as the first dose.  

The Indian Council of Medical Research (ICMR) study compared the vaccine response of these 18 individuals to that of 40 recipients of two doses of Covishield and 40 recipients of two doses of Covaxin.  

The outcome of this study revealed that immunisation with a heterologous combination of vaccines was safe and resulted in better immunogenicity than two doses of homologous vaccination with the same vaccine.  

However, the study is only in the preliminary stage because it is based on only 18 individuals with mixed vaccination, though data shows that heterologous vaccination triggers a better antibody response.  

WHO on vaccine cocktails 

WHO Chief Scientist, Dr Soumya Swaminathan advised against mixing vaccines and called it a 'dangerous trend' without data on health impact.  

Dr Soumya Swaminathan said that such decisions should be left to public health authorities.  

World Health Organization says there is currently limited data on the immunogenicity or efficacy of a 'mix and match' regimen.  

AstraZeneca recommendations indicate that if their vaccine is used, either of the mRNA vaccines - Pfizer or Moderna can be used as a second dose.   

Based on the basic principles of how vaccines work, WHO is of the view that the mix-and-match regimens are likely to work.  

However, WHO says there is a need to analyse the evidence in each of these vaccine combinations before any other recommendations can be made.  

Vaccine mixing theory

Even before COVID-19, studies showed better and broader immune responses with the mixing of vaccines of different types.  

Vaccine platforms may vary in their ability to induce antibody and T-cell response.  

Experts say a platform that induces a predominantly antibody response can be followed by a platform that induces predominantly a T cell response.  

This strategy is usually used with a vector-based platform as the first shot followed by a subunit platform like DNA vaccines.  

Such heterologous strategies are being studied in HIV, malaria, flaviviruses like dengue, HPV, Ebola, and influenza.  

The potential advantages of such a strategy can lead to flexibility in using vaccines based on fluctuation in supplies.  

For COVID-19, experts say heterologous strategies may help to induce combined antibody and cell-mediated immune response.  

Heterologous strategies of vaccination may result in stronger, broader, and long-lasting immunity.   

Experiment around the world  

An Oxford study found giving a second shot of Pfizer vaccine after AstraZeneca four weeks apart will produce a better immune response.  

Another study on Moderna and Novovax vaccine cocktails is also underway, the results of which are awaited.  

Trials on mixing Sputnik V with AstraZeneca's shot revealed no serious side effects and no breakthrough cases among volunteers.  

Germany will offer boosters of Pfizer and Moderna to vulnerable individuals with weak immune systems, regardless of the vaccines used for the first shot.  

South Korean study found that an AstraZeneca shot first and then a Pfizer boosted neutralising antibody levels six times more than two AstraZeneca doses.