NIH Mix and Match Study Suggests mRNA COVID Vaccines May Offer Stronger Boost Than J&J
Executive Summary
Though not designed to facilitate inter-group comparisons, a preprint study of heterologous and homologous boosting with the three US available COVID-19 vaccines indicate Johnson and Johnson primary vaccines may get greater protection from an mRNA booster.
People who got a booster dose of an mRNA COVID-19 vaccine following primary vaccination with Johnson & Johnson’s adenovirus COVID-19 vaccine generated a stronger antibody response than J&J patients boosted with another one of the sponsor’s adenovirus shots, new data from the US National Institutes of Health shows, throwing a possible wrench in J&J’s ability to capitalize on US boosters.
The US Food and Drug Administration’s Vaccine and Related Biological Products Advisory Committee is expected to vote on 15 October on an emergency use authorization for homologous boosting with J&J’s vaccine two to six months following the primary dose of the vaccine. (See sidebar.)
Afterwards, the VRBPAC will hear a presentation from NIH’s National Institutes of Allergy and Infectious Disease (NIAID) on the mix and match booster data, released 13 October on a preprint server, but it is unclear whether the committee will vote or if FDA will soon make formal authorizations on heterologous boosting given that the mix and match data is still coming in. (Also see "Mix and Match COVID Boosters: Time Crunch For Data Review May Mean No Advisory Committee Vote" - Pink Sheet, 7 Oct, 2021.)
Besides possible safety or efficacy benefits, the ability to mix and match could simplify rollout of the booster campaign.
NIAID conducted a Phase I/II adaptive, open-label study in healthy adults who had received either J&J’s vaccine or Moderna, Inc. or Pfizer Inc./BioNTech SE’s mRNA vaccine regimens for COVID-19, testing a booster dose of each of the three vaccines with all three vaccine regimens for a total of nine possible primary vaccine and booster combinations examined. There were 50 people assigned to each of the nine vaccine/booster combinations with half of each group being 18-55 years of age and half being 56 years of age and older.
Boosters were given at least 12 weeks after completion of the primary vaccination series and immunogenicity assessments were performed at day 1 (pre booster vaccination), at day 15 and day 29. Data is not yet available on boosting with Pfizer’s vaccine at day 29.
The study found a substantial increase in neutralizing antibody titers in all study participants following booster vaccination regardless of their booster or primary vaccine series, however, participants who received an mRNA-based booster vaccination had a four-fold increase in the neutralization response more frequently than those who were boosted with J&J’s vaccine.
All groups, except the homologous J&J prime-boost group achieved post-boost neutralizing geometric mean IU50/ml levels of greater than 100, which has previously been correlated with a 90.7% vaccine efficacy for preventing symptomatic disease.
Initial J&J vaccine recipients boosted with J&J had 368.6 geometric mean titers at day 29, compared with J&J vaccine recipients boosted with Moderna who had 2803.1 GMTs at day 29.
Following a boost, all participants had detectable binding antibodies to the Delta variant.
The preprint only has data so far on neutralizing antibody responses against the Delta and Beta variants in people who got the Moderna booster. All but four participants had four-fold or greater increases in ID50 titers to the Delta variant and all but two had four-fold or greater increases in ID50 titers to the Beta variant.
There are several limitations to the study, including that it was not designed to directly compare responses between different booster regimens given the small sample sizes. The demographics of people studied were also not representative of the US population.
Further, there is no established correlate of protection for COVID-19 vaccines that has been proven to predict efficacy, making it unclear what level of antibodies are needed to prevent disease or more severe outcomes. The study also doesn’t take into account the cellular and humoral immune responses generated by the vaccines which, may vary by vaccine type, and the longevity of the booster response.
Another wrench is that the booster dose of Moderna’s vaccine tested was the original 100 mcg dose of the shot used in the primary series, not the half dose version Moderna is proposing for boosting. (Also see "Moderna COVID-19 Vaccine: Booster Study Hits Only One Of Two Immunogenicity Endpoints" - Pink Sheet, 12 Oct, 2021.)
The timing of booster administration in the study was also generally shorter than the 6 month booster time point approved for Pfizer, and proposed by Moderna and by J&J under certain circumstances. (Also see "One Down, Two To Go: Pfizer/BioNTech Booster Decision Creates Pressure For More Extra Shot Authorizations" - Pink Sheet, 24 Sep, 2021.)
No new safety concerns were identified in the study and reactogenicity was similar to that in prior evaluations of the vaccines, NIAID said. Further, reactogenicity did not differ between heterologous and homologous boosts. However, the small sample size and short follow-up period were not sufficient to identify rare or late adverse events following booster vaccination.