1. Neonatal immunity associated with heterologous HIV-1 neutralizing antibody induction in SHIV-infected Rhesus Macaques.
- Author
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Holmes S, Li H, Shen X, Martin M, Tuck R, Chen Y, Giorgi EE, Kirshner HF, Berry M, Van Italie E, Venkatayogi S, Martin Beem JS, Edwards RJ, Mansouri K, Singh A, Kuykendall C, Gurley T, Anthony Moody M, DeNayer N, Demarco T, Denny TN, Wang Y, Evangelous TD, Clinton JT, Hora B, Wagh K, Seaman MS, Saunders KO, Solomotis N, Misamore J, Lewis MG, Wiehe K, Montefiori DC, Shaw GM, and Williams WB
- Subjects
- Animals, Female, Humans, Male, B-Lymphocytes immunology, HIV Infections immunology, HIV Infections virology, T-Lymphocytes, Regulatory immunology, Germinal Center immunology, Disease Models, Animal, Epitopes immunology, Macaca mulatta immunology, HIV-1 immunology, Simian Acquired Immunodeficiency Syndrome immunology, Simian Acquired Immunodeficiency Syndrome virology, Simian Immunodeficiency Virus immunology, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV Antibodies blood, Animals, Newborn
- Abstract
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., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2024
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