Mechanisms of early-life immunity associated with induction of heterologous HIV-1 neutralizing antibodies 9283

Abstract Description A goal of an HIV-1 vaccine is induction of broadly neutralizing antibodies (bnAbs) that prevent infection of different strains. Previous studies have shown that infants and children living with HIV-1 generate bnAbs more frequently than adults. Studying neonate and adult rhesus macaques (RM) infected with simian-HIV (SHIV), we interrogated the permissive immunological environment for bnAb induction in pediatric populations. We studied 11 pairs of SHIV-infected RMs (N = 22), collecting blood and tissue samples up to 24 months post-infection. Viral load was quantified via qPCR of SIV gag RNA copies/mL of plasma. Blood-derived monoclonal (m) Abs and plasma samples were tested for HIV/SHIV neutralization by TZM-bl assay. Lymph node-derived germinal center (GC) B and T cell phenotyping was via flow cytometry. Neonates and adults had similar viral peaks, but neonates maintained 1-2 logs higher mean viremia over time. By 24 months, 7/11 (64%) neonates developed plasma heterologous HIV-1 nAbs, in contrast to 2/11 (18%) adults. From a young RM, we isolated (BEAM-Ab assay 10X Genomics) three mAbs that neutralized up to ∼90% of viral particles in heterologous tier 2 HIV-1 strains, of which two neutralized ∼13% of 119 strains (GM IC50=∼8-11µg/ml). Also, neonates had fewer GC CD4+ T regulatory cells than adults. We defined mechanisms of SHIV immunity that may inform future pediatric vaccine strategies in humans to elicit heterologous HIV-1 nAbs that can mature to bnAbs prior to sexual debut. Topic Categories Viral Immunology (VIR)

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Journal
The Journal of Immunology
Published
2025-11-01
DOI
https://doi.org/10.1093/jimmun/vkaf283.2706
Primary Topic
HIV Research and Treatment
Type
article
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article

Mechanisms of early-life immunity associated with induction of heterologous HIV-1 neutralizing antibodies 9283

M. Anthony Moody, David C. Montefiori, Todd DeMarco, George M. Shaw et al.
The Journal of Immunology
HIV Research and Treatment
article

Mechanisms of early-life immunity associated with induction of heterologous HIV-1 neutralizing antibodies 9283

M. Anthony Moody, David C. Montefiori, Todd DeMarco, George M. Shaw, Bhavna Hora, Hèléne Fradin, Joanne Clinton, Johnathan Misamore, Sommer Holmes, Cindy Kuykendall, Tyler Evangelous, Ryan Tuck, Mark G. Lewis, Mitchell Martin, J E Beem, Katayoun Mansouri, Kevin O. Saunders, Michael S. Seaman, Hui Li, Wilton B. Williams, Elena E. Giorgi, Sravani Venkatayogi, Kshitij Wagh, Yue Chen, Robert J. Edwards, Thomas N. Denny, Madison Berry, Kevin Wiehe, Shaunna Shen, Thaddeus C. Gurley, Elizabeth Van Italie, Nicole DeNayer, Nicholas Solomotis, Yunfei Wang
article en

Abstract

Abstract Description A goal of an HIV-1 vaccine is induction of broadly neutralizing antibodies (bnAbs) that prevent infection of different strains. Previous studies have shown that infants and children living with HIV-1 generate bnAbs more frequently than adults. Studying neonate and adult rhesus macaques (RM) infected with simian-HIV (SHIV), we interrogated the permissive immunological environment for bnAb induction in pediatric populations. We studied 11 pairs of SHIV-infected RMs (N = 22), collecting blood and tissue samples up to 24 months post-infection. Viral load was quantified via qPCR of SIV gag RNA copies/mL of plasma. Blood-derived monoclonal (m) Abs and plasma samples were tested for HIV/SHIV neutralization by TZM-bl assay. Lymph node-derived germinal center (GC) B and T cell phenotyping was via flow cytometry. Neonates and adults had similar viral peaks, but neonates maintained 1-2 logs higher mean viremia over time. By 24 months, 7/11 (64%) neonates developed plasma heterologous HIV-1 nAbs, in contrast to 2/11 (18%) adults. From a young RM, we isolated (BEAM-Ab assay 10X Genomics) three mAbs that neutralized up to ∼90% of viral particles in heterologous tier 2 HIV-1 strains, of which two neutralized ∼13% of 119 strains (GM IC50=∼8-11µg/ml). Also, neonates had fewer GC CD4+ T regulatory cells than adults. We defined mechanisms of SHIV immunity that may inform future pediatric vaccine strategies in humans to elicit heterologous HIV-1 nAbs that can mature to bnAbs prior to sexual debut. Topic Categories Viral Immunology (VIR)

The Journal of ImmunologyVol. 214(Supplement_1)
International Vaccine Institute (KR), Los Alamos National Laboratory (US), Duke University (US), Hadassah Medical Center (IL), Fred Hutch Cancer Center (US), Bioqual (US), University of Pennsylvania (US)
Openalex Percentile: Top 62%
HIV Research and Treatment
DOIOpen Access PDFOpenAlex
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