Mechanisms of early-life immunity associated with induction of heterologous HIV-1 neutralizing antibodies 9283
Year: 2025
Type: article
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)
Source: The Journal of Immunology
Authors: Sommer Holmes, Hui Li, Shaunna Shen, Mitchell Martin, Ryan Tuck, Yue Chen, Elena Giorgi, Hélène Kirshner, Madison Berry, Elizabeth Van Italie, Sravani Venkatayogi, Josh Beem, Robert Edwards, Katayoun Mansouri, Nicole DeNayer, Todd Demarco, Thomas Denny, Cindy Kuykendall, Thaddeus Gurley, Anthony Moody, Yunfei Wang, Tyler Evangelous, John Clinton, Bhavna Hora, Kshitij Wagh, Michael Seaman, Kevin Saunders, Nicholas Solomotis, Johnathan Misamore, Mark Lewis, Kevin Wiehe, David Montefiori, George Shaw, Wilton Williams
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416448610
FWCI:
Cites:
Cited by:
Related to: