Will mixing vaccines fix our world?

Contributed by Dr Prasanna Kumar, CMC, Vellore

As the whole world awaits a solution for the endless miseries of the pandemic, it has driven the political and medical front in search of strategies to enhance herd immunity by increasing the vaccine rollout. However, the shortage of vaccines and increased reporting of side effects for any vaccine, makes them less viable and rules them out of the market. It also opens a dilemma of how to deal with follow-up booster vaccination of banned vaccine. Combining different vaccines offers a great deal on that front but efficacy and safety profiles are unknown. “Heterologous prime-boost “is the method in which different vaccines are combined in the schedule in order to enhance efficacy.

We have the preliminary data from a phase II trial on the safety and efficacy of the "heterologous prime-boost" regimen called the Com Cov trial from the UK. The trial study population consists of 820 adults, 50 years or older, divided in to 2 cohorts with various combinations of ChAd and BNT vaccines both at 28-day and 84-day prime-boost intervals for the general cohort while only 28 days boosting for the immunology cohort. Data on the safety and reactogenicity for 28 days boosting was available and it showed an increase in systemic reactogenicity after the boost dose reported by participants in heterologous vaccine schedules in comparison to homologous vaccine schedules requiring paracetamol usage. The increased reactogenicity is acceptable if immunogenicity is enhanced, however, we need to wait till June 2021 when the complete data set is estimated to be made available for immunogenicity. The only other trial with unpublished data which was reported in one of the Spanish presentations by the authors was the Combivac S trial which compared the immunogenicity between 2 doses of different vaccines with only one dose. 663 participants who had received one dose of the ChAd vaccine were recruited and one group received mRNA based vaccine after 8 weeks while 232 didn’t receive any booster.

Though enhanced immunogenicity was seen after a booster dose of a different vaccine, comparing against single-dose vaccination, sounds illogical as augmented immunogenicity is the norm of any boosting. Hence, this trial also does not answer the research question. The proof we need is whether immunogenicity due to heterologous boosting is comparable to any homologous boosting with acceptable safety. Hence, the strategy still stands untested as of now and needs further data to support the heterologous prime-boost strategy. The world awaits safety and efficacy data on the heterologous prime-boost strategy which is yet to demonstrate better or at least comparable immunogenicity on combination.