SARS-CoV-2 vaccines elicit durable immune responses in infant rhesus macaques
Open Access
- 15 June 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 6 (60)
- https://doi.org/10.1126/sciimmunol.abj3684
Abstract
The inclusion of infants in the SARS-CoV-2 vaccine roll-out is important to prevent severe complications of pediatric SARS-CoV-2 infections and to limit transmission and could possibly be implemented via the global pediatric vaccine schedule. However, age-dependent differences in immune function require careful evaluation of novel vaccines in the pediatric population. Toward this goal, we assessed the safety and immunogenicity of two SARS-CoV-2 vaccines. Two groups of 8 infant rhesus macaques (RMs) were immunized intramuscularly at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or the purified S protein mixed with 3M-052, a synthetic TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. Both vaccines elicited high magnitude IgG binding to RBD, N terminus domain, S1, and S2, ACE2 blocking activity, and high neutralizing antibody titers, all peaking at week 6. S-specific memory B cells were detected by week 4 and S-specific T cell responses were dominated by the production of IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The immune responses for the mRNA-LNP vaccine were of a similar magnitude to those elicited by the Moderna mRNA-1273 vaccine in adults. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines were well-tolerated and highly immunogenic in infant RMs, providing proof-of concept for a pediatric SARS-CoV-2 vaccine with the potential for durable immunity that might decrease the transmission of SARS-CoV-2 and mitigate the ongoing health and socioeconomic impacts of COVID-19.Keywords
Funding Information
- National Institutes of Health (U54 CA260543)
- National Institutes of Health (UM1 AI068618)
- National Cancer Institute (P30 CA016086)
- Office of Research Infrastructure Programs, National Institutes of Health (OD P51D11107)
- NIH (P01 AI117915)
This publication has 92 references indexed in Scilit:
- The Ultra-Potent and Selective TLR8 Agonist VTX-294 Activates Human Newborn and Adult LeukocytesPLOS ONE, 2013
- IgA Response in Preterm Neonates Shows Little Evidence of Antigen-Driven SelectionThe Journal of Immunology, 2012
- Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutininProceedings of the National Academy of Sciences of the United States of America, 2011
- Challenges in infant immunity: implications for responses to infection and vaccinesNature Immunology, 2011
- Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike VariantsPLoS Medicine, 2006
- Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cellsBlood, 2006
- Development of mucosal immunity in the first year of life and relationship to sudden infant death syndromeFEMS Immunology & Medical Microbiology, 2004
- Development of Interleukin-12-Producing Capacity throughout ChildhoodInfection and Immunity, 2002
- Modified Wick Method Using Weck-Cel Sponges for Collection of Human Rectal Secretions and Analysis of Mucosal HIV AntibodyJAIDS Journal of Acquired Immune Deficiency Syndromes, 2000
- In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral VectorScience, 1996