Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Emerging SARS-CoV-2 variants (Beta, Delta) reduce vaccine and infection-induced protection.
• Need for effective strategies to induce neutralizing antibodies against new variants.

Purpose of the Study:

• Evaluate mRNA vaccine regimens for inducing neutralizing titers against SARS-CoV-2 variants.
• Assess primary vaccination vs. booster strategies in nonhuman primates (NHPs).

Main Methods:

• Monovalent and bivalent mRNA vaccines (D614-based, Beta-based) tested in naive and pre-immune NHPs.
• Assessed neutralizing titers against various SARS-CoV-2 variants and SARS-CoV-1.
• Compared mRNA vaccines with recombinant Spike protein boosters.

Main Results:

• Primary vaccination or bivalent regimens yielded modest titers against heterologous variants.
• Booster vaccination in pre-immune NHPs robustly increased neutralizing titers and breadth.
• Breadth included neutralization of SARS-CoV-1 and variants with E484K mutations.
• Both mRNA and subunit protein boosters expanded neutralizing antibody breadth.

Conclusions:

• A third vaccination (booster) is crucial for enhancing antibody titers and breadth against SARS-CoV-2 variants.
• Booster strategy effectively addresses variants of concern, including Beta and Gamma.
• Broadly neutralizing antibody responses can be induced irrespective of vaccine sequence or modality.