Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.

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  • Additional Information
    • Source:
      Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : American Association for the Advancement of Science
    • Subject Terms:
      COVID-19* ; Viral Vaccines*; Animals ; Humans ; Infant ; SARS-CoV-2 ; COVID-19 Vaccines ; Macaca mulatta ; BNT162 Vaccine ; Antibodies, Viral ; Antibodies, Neutralizing
    • Abstract:
      The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.
    • Grant Information:
      P01 CA019014 United States CA NCI NIH HHS; U54 CA260543 United States CA NCI NIH HHS; P30 CA016086 United States CA NCI NIH HHS; P01 AI117915 United States AI NIAID NIH HHS; P30 AI050410 United States AI NIAID NIH HHS; HHSN272201800004C United States AI NIAID NIH HHS; UM1 AI068618 United States AI NIAID NIH HHS; P51 OD011107 United States OD NIH HHS
    • Accession Number:
      0 (COVID-19 Vaccines)
      0 (Viral Vaccines)
      0 (BNT162 Vaccine)
      0 (Antibodies, Viral)
      0 (Antibodies, Neutralizing)
    • Subject Terms:
      SARS-CoV-2 variants
    • Publication Date:
      Date Created: 20221201 Date Completed: 20230303 Latest Revision: 20230408
    • Publication Date:
      20230410
    • Accession Number:
      PMC9765459
    • Accession Number:
      10.1126/scitranslmed.add6383
    • Accession Number:
      36454813