Neonatal immunity associated with heterologous HIV-1 neutralizing antibody induction in SHIV-infected Rhesus Macaques
The details of the pediatric immune system that supports induction of antibodies capable of neutralizing geographically-diverse or heterologous HIV-1 is currently unclear. Here we explore the pediatric immune environment in neonatal macaque undergoing Simian-HIV infection. Simian-HIV infection of 11 pairs of therapy-naive dams and infant rhesus macaques for 24 months results in heterologous HIV-1 neutralizing antibodies in 64% of young macaques compared to 18% of adult macaques. Heterologous HIV-1 neutralizing antibodies emerge by 12 months post-infection in young macaques, in association with lower expression of immunosuppressive genes, fewer germinal center CD4 + T regulatory cells, and a lower ratio of CD4 + T follicular regulatory to helper cells. Antibodies from peripheral blood B cells in two young macaques following SHIV infection neutralize 13% of 119 heterologous HIV-1 strains and map to regions of canonical broadly neutralizing antibody epitopes on the envelope surface protein. Here we show that pediatric immunity to SHIV infection in a macaque model may inform vaccine strategies to induce effective HIV-1 neutralizing antibodies in infants and children prior to viral exposure.
Authors
- M. Anthony Moody
- David C. Montefiori (ORCID: https://orcid.org/0000-0003-0856-6319)
- Thomas N. Denny (ORCID: https://orcid.org/0000-0002-7364-8276)
- Todd DeMarco
- Bhavna Hora
- Hèléne Fradin (ORCID: https://orcid.org/0000-0003-4110-0983)
- Joanne Clinton
- Johnathan Misamore
- Sommer Holmes (ORCID: https://orcid.org/0009-0009-8205-2616)
- Cindy Kuykendall
- Tyler Evangelous (ORCID: https://orcid.org/0000-0001-9858-2114)
- Ryan Tuck (ORCID: https://orcid.org/0000-0003-0697-0924)
- Yunfei Wang (ORCID: https://orcid.org/0000-0002-3205-6338)
- Joshua S. Martin Beem
- Mark G. Lewis (ORCID: https://orcid.org/0000-0001-7852-0135)
- Xiaoying Shen (ORCID: https://orcid.org/0000-0002-8387-3952)
- Mitchell Martin (ORCID: https://orcid.org/0000-0002-1043-4465)
- Katayoun Mansouri (ORCID: https://orcid.org/0000-0001-6232-7330)
- Kevin J. Wiehe (ORCID: https://orcid.org/0000-0001-9933-9618)
- Kevin O. Saunders (ORCID: https://orcid.org/0000-0001-7399-7954)
- Michael S. Seaman (ORCID: https://orcid.org/0000-0001-6444-3562)
- Hui Li (ORCID: https://orcid.org/0000-0002-4863-2950)
- Wilton B. Williams (ORCID: https://orcid.org/0000-0002-2970-7259)
- Elena E. Giorgi (ORCID: https://orcid.org/0000-0003-2968-1033)
- Sravani Venkatayogi (ORCID: https://orcid.org/0000-0001-8976-6827)
- Kshitij Wagh (ORCID: https://orcid.org/0000-0001-7552-6582)
- Yue Chen (ORCID: https://orcid.org/0000-0002-5413-4456)
- Ajay Singh (ORCID: https://orcid.org/0000-0001-7751-2934)
- Robert J. Edwards (ORCID: https://orcid.org/0000-0003-4446-1194)
- George M. Shaw
- Madison Berry
- Thaddeus C. Gurley
- Elizabeth Van Italie
- Nicole DeNayer
- Nicholas Solomotis
Institutions
- Beth Israel Deaconess Medical Center (US)
- Los Alamos National Laboratory (US)
- Harvard University (US)
- Duke University (US)
- Fred Hutch Cancer Center (US)
- Bioqual (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41467-024-54753-6
- Citations
- 3
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.88
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- School of Medicine, Duke University
- National Institute of Allergy and Infectious Diseases