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

Abstract

Background 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. Methods In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we 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. Results Homologous or heterologous booster vaccination 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. Conclusions 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. (Funded by the Netherlands Organization for Health Research and Development ZonMw; SWITCH ClinicalTrials.gov number, NCT04927936 .)

Divergent SARS-CoV-2 Omicron–reactive T and B cell responses in COVID-19 vaccine recipients

“…The SWITCH trial was approved by the institutional review board of the Erasmus MC (MEC 2021-0132) and local review boards of participating centres. The study was registered at clinicaltrials.gov (NCT04927936) ( 40 ). All studies adhere to the principles of the Declaration of Helsinki, and written informed consent was obtained from every participant, patient or legal representative.…”

“…Additional serum and PBMC samples were obtained from 9 mRNA1273 / mRNA-1273-primed participants at 14 days after booster vaccination with BNT162b2. Participants of the SWITCH trial were vaccinated with Ad26.COV2.S, followed by a BNT162b2 boost (85 day interval) ( 40 ). Serum samples were obtained 28 days after the booster vaccination ( Fig.…”

COVID-19 vaccines in patients with cancer: immunogenicity, efficacy and safety

“…The use of booster vaccines in patients with cancer is further supported by the observation that titres after vaccination are higher in those previously infected with SARS-CoV-2 than in infection-naive patients 65 , 141 . The available evidence suggests that heterologous vaccination is superior to homologous vaccination, at least in those originally vaccinated with adenovirus-vectored vaccines 142 . Interestingly, vaccination with an adenovirus-vectored vaccine followed by an mRNA vaccine seems to be more effective than a homologous adenovirus-vectored vaccination regimen, in contrast to the experience with mRNA vaccines followed by an adenovirus-vectored vaccine 37 (Fig.…”

Effect of booster vaccination against Delta and Omicron variants in Iceland

“…Due to a high incidence of SARS-CoV-2 infections among those who received one dose of Ad26.COV2.S vaccine, the Chief epidemiologist in Iceland issued a recommendation of a booster dose of mRNA vaccine to all Ad26.COV2.S vaccine recipients in early August 2021, which has been shown to be effective in raising antibody levels. 10,11 Following this, booster vaccinations were recommended to the general public regardless of the vaccine they had initially received. 12 The first case of the B.1.1.529 (omicron) VOC in Iceland was confirmed on December 1, 2021, and spread rapidly, reaching 90% of daily confirmed cases by January 6, 2022.…”