evidence: Pfizer and BioNTech co-developed five mRNA vaccine candidates that encode variants of the spike protein antigen119. The two lead candidates, BNT162b1 and BNT162b2, use LNPs that are formulated using Acuitas Therapeutics’ ionizable lipid ALC-0315 and a nucleoside-modified mRNA in which all uridines are replaced by N1-methylpseudouridine to enhance mRNA translation. BNT162b1 encodes a trimerized, secreted version of the spike protein’s receptor-binding domain, whereas BNT162b2 encodes the full-length SARS-CoV-2 spike glycoprotein with two proline substitutions in the S2 subunit, which lock the protein in its prefusion conformation120,121. In preclinical studies in rhesus macaques, two 100 μg doses of BNT162b2 delivered 21 days apart elicited neutralizing antibody titres 10.2–18.0 times higher than convalescent patient serum as well as strong CD4+ and CD8+ T cell responses122. In phase I trials of the two candidates, two 30 μg doses delivered 21 days apart induced high antibody and neutralizing titres and a robust CD4+ and CD8+ response with mild to moderate adverse events27,28,123,124. Both candidates were well tolerated and efficacious, but only the BNT162b2 vaccine advanced to phase II/III trials owing to its milder systemic and local adverse reactions124. [...] Pfizer and BioNTech Announce an Agreement with U.S. Government for up to 600 Million Doses of mRNA-based Vaccine Candidate Against SARS-CoV-2:https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-agreement-us-government-600