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

Publication ,  Journal Article
Milligan, EC; Olstad, K; Williams, CA; Mallory, M; Cano, P; Cross, KA; Munt, JE; Garrido, C; Lindesmith, L; Watanabe, J; Usachenko, JL; Gao, H ...
Published in: Sci Transl Med
March 2023

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.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

March 2023

Volume

15

Issue

685

Start / End Page

eadd6383

Location

United States

Related Subject Headings

  • Viral Vaccines
  • SARS-CoV-2
  • Macaca mulatta
  • Infant
  • Humans
  • COVID-19 Vaccines
  • COVID-19
  • BNT162 Vaccine
  • Antibodies, Viral
  • Antibodies, Neutralizing
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Milligan, E. C., Olstad, K., Williams, C. A., Mallory, M., Cano, P., Cross, K. A., … De Paris, K. (2023). Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med, 15(685), eadd6383. https://doi.org/10.1126/scitranslmed.add6383
Milligan, Emma C., Katherine Olstad, Caitlin A. Williams, Michael Mallory, Patricio Cano, Kaitlyn A. Cross, Jennifer E. Munt, et al. “Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.Sci Transl Med 15, no. 685 (March 2023): eadd6383. https://doi.org/10.1126/scitranslmed.add6383.
Milligan EC, Olstad K, Williams CA, Mallory M, Cano P, Cross KA, et al. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med. 2023 Mar;15(685):eadd6383.
Milligan, Emma C., et al. “Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later.Sci Transl Med, vol. 15, no. 685, Mar. 2023, p. eadd6383. Pubmed, doi:10.1126/scitranslmed.add6383.
Milligan EC, Olstad K, Williams CA, Mallory M, Cano P, Cross KA, Munt JE, Garrido C, Lindesmith L, Watanabe J, Usachenko JL, Hopkins L, Immareddy R, Shaan Lakshmanappa Y, Elizaldi SR, Roh JW, Sammak RL, Pollard RE, Yee JL, Herbek S, Scobey T, Miehlke D, Fouda G, Ferrari G, Gao H, Shen X, Kozlowski PA, Montefiori D, Hudgens MG, Edwards DK, Carfi A, Corbett KS, Graham BS, Fox CB, Tomai M, Iyer SS, Baric R, Reader R, Dittmer DP, Van Rompay KKA, Permar SR, De Paris K. Infant rhesus macaques immunized against SARS-CoV-2 are protected against heterologous virus challenge 1 year later. Sci Transl Med. 2023 Mar;15(685):eadd6383.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

March 2023

Volume

15

Issue

685

Start / End Page

eadd6383

Location

United States

Related Subject Headings

  • Viral Vaccines
  • SARS-CoV-2
  • Macaca mulatta
  • Infant
  • Humans
  • COVID-19 Vaccines
  • COVID-19
  • BNT162 Vaccine
  • Antibodies, Viral
  • Antibodies, Neutralizing