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

Publication ,  Journal Article
Dennis, M; Eudailey, J; Pollara, J; McMillan, AS; Cronin, KD; Saha, PT; Curtis, AD; Hudgens, MG; Fouda, GG; Ferrari, G; Alam, M; De Paris, K ...
Published in: J Virol
March 1, 2019

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.

Duke Scholars

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

March 1, 2019

Volume

93

Issue

5

Location

United States

Related Subject Headings

  • Virology
  • Vaccinia virus
  • Vaccination
  • Macaca mulatta
  • Infectious Disease Transmission, Vertical
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Epitopes
 

Citation

APA
Chicago
ICMJE
MLA
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Dennis, M., Eudailey, J., Pollara, J., McMillan, A. S., Cronin, K. D., Saha, P. T., … Shen, X. (2019). Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques. J Virol, 93(5). https://doi.org/10.1128/JVI.01783-18
Dennis, Maria, Joshua Eudailey, Justin Pollara, Arthur S. McMillan, Kenneth D. Cronin, Pooja T. Saha, Alan D. Curtis, et al. “Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques.J Virol 93, no. 5 (March 1, 2019). https://doi.org/10.1128/JVI.01783-18.
Dennis 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. Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques. J Virol. 2019 Mar 1;93(5).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

March 1, 2019

Volume

93

Issue

5

Location

United States

Related Subject Headings

  • Virology
  • Vaccinia virus
  • Vaccination
  • Macaca mulatta
  • Infectious Disease Transmission, Vertical
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Epitopes