Publication Date
9-1-2023
Journal
Nature Medicine
DOI
10.1038/s41591-023-02503-4
PMID
37640860
PMCID
PMC10504073
PubMedCentral® Posted Date
8-28-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, COVID-19 Vaccines, SARS-CoV-2, COVID-19, Broadly Neutralizing Antibodies, Translational research, RNA vaccines, Randomized controlled trials
Abstract
Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037.
Included in
Clinical Epidemiology Commons, COVID-19 Commons, Critical Care Commons, Epidemiology Commons, Influenza Humans Commons, Influenza Virus Vaccines Commons, Medical Sciences Commons, Pediatrics Commons