First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial

Aug 13, 2024EBioMedicine

First Omicron COVID-19 infection as a strong immune booster in people vaccinated with mRNA shots: final results from the first phase of a clinical trial

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Abstract

71% of participants reported first SARS-CoV-2 Omicron infection by the end of the study.

Heterologous booster vaccination with mRNA-1273 resulted in a significantly higher mean wildtype SARS-CoV-2 anti-S-RBD antibody level at day 180 compared to homologous vaccination with BNT162b2.
Participants who experienced breakthrough infections during the Omicron BA.1/2 wave exhibited significantly higher antibody levels against wildtype SARS-CoV-2 and neutralization capacity against BA.1 and pre-emergent BA.5 than infection-naïve participants.
Wildtype SARS-CoV-2 anti-S-RBD antibody levels declined significantly after six months, regardless of whether participants had hybrid immunity from infection or vaccination.
Similar proportions of Omicron infections were observed between the homologous and heterologous booster groups.

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BACKGROUND: Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy.

METHODS: We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants.

FINDINGS: 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection.

INTERPRETATION: Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster.

FUNDING: Singapore NMRC, USFDA, MRC.

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First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial

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