With the Indian drug regulator greenlighting Corbevax as a booster dose for all adults above 18 years who have received two doses of either Covishield or Covaxin as part of primary vaccination, a heterologous booster shot has come a step closer to being administered to people. Though booster shots have been administered since January 10 beginning with health-care and frontline workers, and people over 60 with comorbidities, India has been using the same vaccine for both primary vaccination and booster (homologous boosting). In clinical trials, a booster dose using a vaccine that is different from the one used for primary vaccination — technically called heterologous boosting — produced higher immune responses when compared with a same vaccine for primary and booster vaccination. A trial by the Christian Medical College, Vellore, too found the same result. As expected, Bio E’s phase-3 heterologous booster vaccine trial using Corbevax in people who have received two doses of either Covaxin or Covishield did produce significantly higher immune responses. But with the control group not receiving a homologous booster shot but only a placebo, the trial failed to bring out the enhanced immune responses by using Corbevax as a heterologous booster. Any vaccine administered as a booster — immaterial of being homologous or heterologous — months after primary vaccination will, by default, increase the immune responses. The trial has thus only shown that Corbevax as a heterologous booster increases the immune responses but failed to show that heterologous boosting with this vaccine produces superior immune responses than homologous boosting with Covishield or Covaxin. It is all the more surprising that the booster trial used a placebo for the control arm as even the phase-3 clinical trial to study the immunogenicity of Corbevax for primary vaccination used the comparator vaccine Covishield for the control group.
With Corbevax being approved as a heterologous booster based on a poorly designed heterologous booster trial, the drug regulator can be expected to soon greenlight Covishield and Covaxin as heterologous boosters based on the results of the CMC Vellore trial. Especially as the trial clearly demonstrated the advantages of heterologous boosting compared with using the same vaccine for primary vaccination and boosting. While the National Technical Advisory Group on Immunisation (NTAGI) is quite likely to approve Corbevax as a heterologous booster shot without much delay, it remains to be seen whether it greenlights it for all adults above 18 years. Given the greater likelihood of NTAGI approving Corbevax as a heterologous booster, the Government is not likely to side step the expert group, as in mid-March. As booster shots have been rolled out for all adults above 18 years, the Government should not hurry to approve Corbevax without NTAGI’s nod.
