Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques.

TitleCoadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques.
Publication TypeJournal Article
Year of Publication2019
AuthorsDennis M, Eudailey J, Pollara J, McMillan AS, Cronin KD, Saha PT, Curtis AD, Hudgens MG, Fouda GG, Ferrari G, Alam M, Van Rompay KKA, De Paris K, Permar S, Shen X
JournalJ Virol
Volume93
Issue5
Date Published2019 Mar 01
ISSN1098-5514
KeywordsAIDS Vaccines, Animals, Antibodies, Neutralizing, Antibody Formation, Epitopes, HIV Antibodies, HIV Envelope Protein gp120, HIV Infections, HIV-1, Infectious Disease Transmission, Vertical, Macaca mulatta, Vaccination, Vaccinia virus
Abstract

Prevention of mother-to-child transmission (MTCT) is an indispensable component in combatting the global AIDS epidemic. A combination of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provide protection of infants against MTCT from birth through the breastfeeding period and could prime the immune system for lifelong immunity. In this study, we investigate the impact of a single infusion of CD4 binding site (CD4bs) bnAb administered at birth on de novo antibody responses elicited by concurrent active HIV envelope vaccination. Four groups of infant macaques received active immunizations with subunit Env protein or modified vaccinia Ankara (MVA)-vectored Env and subunit Env protein, with or without a single intravenous coadministration of CH31 bnAb at birth. Vaccinated animals were monitored to evaluate binding and functional antibody responses elicited by the active vaccinations. Despite achieving plasma concentrations that were able to neutralize tier 2 viruses, coadministration of CH31 did not have a large impact on the kinetics, magnitude, specificity, or avidity of vaccine-elicited binding or functional antibody responses, including epitope specificity, the development of CD4bs antibodies, neutralization, binding to infected cells, or antibody-dependent cell-mediated cytotoxicity (ADCC). We conclude that infusion of CD4bs bnAb CH31 at birth does not interfere with de novo antibody responses to active vaccination and that a combination of passive bnAb infusion and active HIV-1 Env vaccination is a viable strategy for immediate and prolonged protection against MTCT.IMPORTANCE Our study is the first to evaluate the impact of passive infusion of a broadly neutralizing antibody in newborns on the de novo development of antibody responses following active vaccinations in infancy. We demonstrated the safety and the feasibility of bnAb administration to achieve biologically relevant levels of the antibody and showed that the passive infusion did not impair the de novo antibody production following HIV-1 Env vaccination. Our study paves the way for further investigations of the combination strategy using passive plus active immunization to provide protection of infants born to HIV-1-positive mothers over the entire period of risk for mother-to-child transmission.

DOI10.1128/JVI.01783-18
Alternate JournalJ Virol
PubMed ID30541851
PubMed Central IDPMC6384077
Grant ListK01 OD024877 / OD / NIH HHS / United States
P01 AI117915 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P51 OD011107 / OD / NIH HHS / United States