| Randomised double-blinded placebo-controlled trial  

Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming

The Ad26.COV2.S vaccine, which was approved as a single-shot immunization regimen, has been shown to be effective against severe coronavirus disease 2019.

However, this vaccine induces lower severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S)–specific antibody levels than those induced by messenger RNA (mRNA)–based vaccines. The immunogenicity and reactogenicity of a homologous or heterologous booster in persons who have received an Ad26.COV2.S priming dose are unclear. In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, the authors assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The participants were assigned to receive no booster, an Ad26.COV2.S booster, an mRNA-1273 booster, or a BNT162b2 booster. The primary end point was the level of S-specific binding antibodies, and the secondary end points were the levels of neutralizing antibodies, S-specific T-cell responses, and reactogenicity. A post hoc analysis was performed to compare mRNA-1273 boosting with BNT162b2 boosting. Homologous or heterologous booster vaccination in 434 participants resulted in higher levels of S-specific binding antibodies, neutralizing antibodies, and T-cell responses than a single Ad26.COV2.S vaccination. The increase in binding antibodies was significantly larger with heterologous regimens that included mRNA-based vaccines than with the homologous booster. The mRNA-1273 booster was most immunogenic and was associated with higher reactogenicity than the BNT162b2 and Ad26.COV2.S boosters. Local and systemic reactions were generally mild to moderate in the first 2 days after booster administration. The authors concluded that
the Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting.
Sablerolles RSG, Rietdijk WJR, Goorhuis A, Postma DF, Visser LG, Geers D, Schmitz KS, Garcia Garrido HM, Koopmans MPG, Dalm VASH, Kootstra NA, Huckriede ALW, Lafeber M, van Baarle D, GeurtsvanKessel CH, de Vries RD, van der Kuy PHM; SWITCH Research Group. Immunogenicity and Reactogenicity of Vaccine Boosters after Ad26.COV2.S Priming. N Engl J Med. 2022 Jan 19

doi: 10.1056/NEJMoa2116747.