ABSTRACT
BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity has raised the need for booster vaccinations. However, which combination of COVID-19 vaccines offers the strongest immune response against Omicron variant is unknown. METHODS: This randomized, subject-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. 100 BNT162b2-vaccinated individuals were enrolled and randomized 1: 1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; 'BBB') or heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; 'BBM'). Primary endpoint was the level of neutralizing antibodies against SARS-CoV-2 wild-type and VOCs at Day 28. RESULTS: 51 participants were allocated to BBB and 49 to BBM; 50 and 48 respectively were analyzed for safety and immunogenicity outcomes. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22,382â â IU/mL 95% CI, 18,210 to 27,517) vs BBM (29,751â â IU/mL 95% CI, 25,281 to 35,011, p = 0.034) as was the median level of neutralizing antibodies: BBB 99.0% (IQR 97.9 to 99.3%) vs BBM 99.3% (IQR 98.8 to 99.5%, p = 0.021). On sub-group analysis, significant differences in mean spike antibody titer and live Omicron neutralization titer was only observed in older adults. Median surrogate neutralizing antibody level against all VOCs was also significantly higher with BBM in older adults, and against Omicron was BBB 72.8% (IQR 54.0 to 84.7%) vs BBM 84.3% (IQR 78.1 to 88.7%, p = 0.0073). Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination induced a stronger neutralizing response against the Omicron variant in older individuals compared with homologous BNT123b2.
ABSTRACT
Vaccines that are broadly cross-protective against current and future SARS-CoV-2 variants of concern (VoC) or across the sarbecoviruses subgenus remain a priority for public health. Virus neutralization is the best available correlate of protection. To define the magnitude and breadth of cross-neutralization in individuals with different exposure to SARS-CoV-2 infection and vaccination, we here use a multiplex surrogate neutralization assay based on virus spike receptor binding domains of multiple SARS-CoV-2 VoC, as well as related bat and pangolin viruses. We include sera from cohorts of individuals vaccinated with two or three doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (Coronavac or Sinopharm) vaccines with or without a history of previous SARS-CoV-2 or SARS-CoV-1 infection. SARS-CoV-2 or SARS-CoV-1 infection followed by BNT162b2 vaccine, Omicron BA.2 breakthrough infection following BNT162b2 vaccine or a third dose of BNT162b2 following two doses of BNT162b2 or Coronavac elicit the highest and broadest neutralization across VoCs. For both breadth and magnitude of neutralization across all sarbecoviruses, those infected with SARS-CoV-1 immunized with BNT162b2 outperform all other combinations of infection and/or vaccination. These data may inform vaccine design strategies for generating broadly neutralizing antibodies to SARS-CoV-2 variants or across the sarbecovirus subgenus.
Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , SARS-CoV-2 , Neutralization Tests , Antibodies, Viral , Broadly Neutralizing Antibodies , BNT162 Vaccine , COVID-19/prevention & control , Receptors, Virus , RNA, MessengerABSTRACT
The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.