BNT162b vaccines protect rhesus macaques from SARS-CoV-2

Area of Science:

• Vaccinology
• Virology
• Immunology

Background:

• Urgent need for safe and effective COVID-19 vaccines to immunize large populations.
• Development of novel vaccine platforms is critical for pandemic response.
• Messenger RNA (mRNA) technology offers a promising approach for rapid vaccine development.

Purpose of the Study:

• To report the preclinical development of two mRNA-based COVID-19 vaccine candidates, BNT162b1 and BNT162b2.
• To evaluate the immunogenicity and protective efficacy of these vaccine candidates in preclinical models.
• To assess the potential of these candidates for large-scale human immunization.

Main Methods:

• Development of two vaccine candidates (BNT162b1 and BNT162b2) using nucleoside-modified mRNA encoding SARS-CoV-2 spike glycoprotein immunogens.
• Formulation of mRNA candidates in lipid nanoparticles.
• Evaluation of immunogenicity (antibody and T cell responses) in mice and non-human primates (rhesus macaques).
• Assessment of protective efficacy against SARS-CoV-2 challenge in rhesus macaques.

Main Results:

• Single intramuscular dose of either vaccine candidate elicited dose-dependent antibody responses and high virus-entry inhibition titres in mice.
• Prime-boost vaccination in rhesus macaques induced SARS-CoV-2-neutralizing titres significantly higher than those in convalescent human sera.
• Vaccine candidates protected macaques against SARS-CoV-2 challenge, with BNT162b2 showing protection in the lower respiratory tract and no disease enhancement.

Conclusions:

• BNT162b1 and BNT162b2 are promising COVID-19 vaccine candidates with strong preclinical immunogenicity and efficacy.
• BNT162b2 demonstrated particular efficacy in protecting the respiratory tract and safety without disease enhancement.
• Both candidates are advancing to human clinical trials, including Phase I, II, and III studies.