ABSTRACT
Background Bivalent mRNA-based COVID-19 vaccines encoding the ancestral and Omicron spike protein were developed as a countermeasure against antigenically distinct SARS-CoV-2 variants. We compared the (variant-specific) immunogenicity and reactogenicity of mRNA-based bivalent Omicron BA.1 vaccines in individuals who were primed with adenovirus- or mRNA-based vaccines. Methods In this open-label, multicenter, randomized, controlled trial, healthcare workers primed with Ad26.COV2.S or mRNA-based vaccines were boosted with mRNA-1273.214 or BNT162b2 OMI BA.1. The primary endpoint was the fold change in S1-specific IgG antibodies pre- and 28 days after booster vaccination. Secondary outcomes were fast response, (antibody levels on day 7), reactogenicity, neutralization of circulating variants and (cross-reactive) SARS-CoV-2-specific T-cell responses. Findings No effect of different priming regimens was observed on bivalent vaccination boosted S1-specific IgG antibodies. The largest increase in S1-specific IgG antibodies occurred between day 0 and 7 after bivalent booster. Neutralizing antibodies targeting the variants in the bivalent vaccine (ancestral SARS-CoV-2 and Omicron BA.1) were boosted. In addition, neutralizing antibodies against the circulating Omicron BA.5 variant increased after BA.1 bivalent booster. T-cell responses were boosted and retained reactivity with variants from the Omicron sub-lineage. Interpretation Bivalent booster vaccination with mRNA-1273.214 or BNT162b2 OMI BA.1 resulted in a rapid recall of humoral and cellular immune responses independent of the initial priming regimen. Although no preferential boosting of variant-specific responses was observed, the induced antibodies and T-cells cross-reacted with Omicron BA.1 and BA.5. It remains crucial to monitor immunity at the population level, and simultaneously antigenic drift at the virus level, to determine the necessity (and timing) of COVID-19 booster vaccinations.
Subject(s)
COVID-19ABSTRACT
A large proportion of the global population received a single dose of the Ad26.COV2.S coronavirus disease-2019 (COVID-19) vaccine as priming vaccination, which was shown to provide protection against moderate to severe COVID-19. However, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants that harbor immune-evasive mutations in the spike protein led to the recommendation of booster vaccinations after Ad26.COV2.S priming. Recent studies showed that heterologous booster vaccination with an mRNA-based vaccine following Ad26.COV2.S priming leads to high antibody levels. However, how heterologous booster vaccination affects other functional aspects of the immune response remains unknown. Here, we performed immunological profiling on samples obtained from Ad26.COV2.S-vaccinated individuals before and after a homologous (Ad26.COV2.S) or heterologous (mRNA-1273 or BNT162b2) booster vaccination. Both homologous and heterologous booster vaccination increased antibodies with multiple functionalities towards ancestral SARS-CoV-2, the Delta and Omicron BA.1 variants. Especially, mRNA-based booster vaccination induced high levels of neutralizing antibodies and antibodies with various Fc-mediated effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. In contrast, T cell responses were similar in magnitude following homologous or heterologous booster vaccination, and retained functionality towards Delta and Omicron BA.1. However, only heterologous booster vaccination with an mRNA-based vaccine led to the expansion of SARS-CoV-2-specific T cell clones, without an increase in the breadth of the T cell repertoire as assessed by T cell receptor sequencing. In conclusion, we show that Ad26.COV2.S priming vaccination provides a solid immunological base for heterologous boosting with an mRNA-based COVID-19 vaccine, increasing humoral and cellular responses targeting newly emerging variants of concern.
Subject(s)
Coronavirus Infections , Drug-Related Side Effects and Adverse Reactions , COVID-19ABSTRACT
Background In face of the developing COVID-19 pandemic with a need for rapid and practical vaccination strategies, Ad26.COV2.S was approved as single shot immunization regimen. While effective against severe COVID-19, Ad26.COV2.S vaccination induces lower SARS-CoV-2-specific antibody levels compared to its mRNA-based counterparts. To support decision making on the need for booster vaccinations in Ad26.COV2.S-primed individuals, we assessed the immunogenicity and reactogenicity of homologous and heterologous booster vaccinations in Ad26.COV2.S-primed health care workers (HCWs). Methods The SWITCH trial is a single-(participant)-blinded, multi-center, randomized controlled trial among 434 HCWs who received a single Ad26.COV2.S vaccination. HCWs were randomized to no boost, Ad26.COV2.S boost, mRNA-1273 boost, or BNT162b2 boost. We assessed the level of SARS-CoV-2-specific binding antibodies, neutralizing antibodies against infectious virus, SARS-CoV-2-specific T-cell responses, and reactogenicity. Results Homologous and heterologous booster vaccinations resulted in an increase in SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cell responses when compared to single Ad26.COV.2.S vaccination. In comparison with the homologous boost, the increase was significantly larger in heterologous regimens with the mRNA-based vaccines. mRNA-1273 boosting was most immunogenic, associated with higher reactogenicity. Only mild to moderate local and systemic reactions were observed on the first two days following booster. Conclusions Boosting of Ad26.COV2.S-primed HCWs was well-tolerated and immunogenic. Strongest responses were detected after boosting with mRNA-based vaccines. Based on our data, efficacy on infection and transmission of boosters is expected. In addition to efficacy, decision making on boost vaccinations should include timing, target population, level of SARS CoV-2 circulation, and the global inequity in vaccine access. Trial registration. Funded by ZonMW (10430072110001); ClinicalTrials.gov number, NCT04927936.