The emergence of the SARS-CoV-2 Delta and Omicron virus variants has raised the importance of booster vaccines. The broader immunity from a third dose of COVID vaccine appears to provide better protection against both the original virus strain and new variants. In addition, a few of the vaccines available throughout the world, particularly the single dose Johnson and Johnson vaccine, provide protection that essentially goes away in six months making a booster dosage crucial.
Most government agencies, including The United States CDC, have recommended getting a booster with any COVID-19 vaccine regardless of what your initial dose involved. But there has been no direct comparison about the efficacy and safety of different booster regiments.
This week, a new study in the journal Lancet did a direct comparison of seven different third dose booster vaccines in combination with primary vaccinations. The study was performed in the UK, so it involved primary immunization with the Pfizer/NBioTech and the AstraZeneca chimpanzee virus vaccine, since those were the two vaccines first approved in that country.
The researchers compared seven different vaccines as boosters. All were given at the recommended booser dose, which is often different from the initial dose (Moderna, for example, is ½ the amount given in initial two doses).
In addition to AstraZeneca and Pfizer, they used two other brands approved in the U.S. — Johnson & Johnson and Moderna. They also examined Novavax, which is approved in parts of Europe, and two vaccines not authorized anywhere: an mRNA vaccine from CureVac (which failed clinical trial as a primary vaccine) and a vaccine from Valneva made from inactivated coronaviruses. As a control group some of the volunteers were given a meningitis vaccine instead of a COVID-19 vaccine.
The study was well controlled, and all groups appeared equal in the numbers and types of individuals immunized. The investigators looked at antibody and cellular immune responses, as well as adverse reactions (headaches, fevers, pain, etc.) and compared all the outcomes using appropriate statistics.
While the authors and UK investigators hailed the results as indicating “all the boosters worked,” the efficacy differences between the regimens were highly significant. The improvements in antibody responses ranged from 30 to 1,000-fold!
The clear winners were the mRNA vaccines that gave the strongest antibody improvements and cellular immune responses as boosters. These vaccines also gave the best overall immunity of all the combinations when the Pfizer vaccine was given as the initial two doses. The combinations that were least effective involved the unapproved vaccines from Valneva and CureVac. Novavax was much better than those vaccines, but not as good as the Moderna and Pfizer.
Overall the side effects from booster vaccines were minimal and did not involve any serious reactions, but differences were present. The adenovirus-based vaccines from AstraZeneca and Johnson and Johnson showed only moderate efficacy to boost immunity (not as effective as either Pfizer or Moderna), but had worse side effects, especially when boosting the Pfizer/BNT primary vaccine. Only the most immunogenic and reactive mRNA vaccine, Moderna, approached this level of side effects.
While the intensity of immunity needed to protect against COVID-19 is not exactly defined, in general most immunologists feel (and there is data to support this) that a higher the level of immunity results in better protection. So, it is likely that the improved booster immunity seen with the best combinations tested could lead to significantly better defense against COVID infection.
Bottom line: get Pfizer or Moderna as your booster shot no matter what vaccine you originally received.