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Clin Vaccine Immunol. 2017 Oct 5;24(10). pii: e00231-17. doi: 10.1128/CVI.00231-17. Print 2017 Oct.

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques.

Author information

1
Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
2
Duke University Medical Center, Duke Human Vaccine Institute, Durham, North Carolina, USA.
3
Gillings School of Public Health and Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
4
California National Primate Research Center, University of California at Davis, Davis, California, USA.
5
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
6
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
7
Department of Microbiology and Immunology and Center for AIDS Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA abelk@med.unc.edu.

Abstract

Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infants. Thus, a pediatric vaccine is needed to eradicate oral HIV infections in newborns and infants. Utilizing the infant rhesus macaque model, we compared 3 different vaccine regimens: (i) HIV envelope (Env) protein only, (ii) poxvirus vector (modified vaccinia virus Ankara [MVA])-HIV Env prime and HIV Env boost, and (iii) coadministration of HIV Env and MVA-HIV Env at all time points. The vaccines were administered with an accelerated, 3-week-interval regimen starting at birth for early induction of highly functional HIV Env-specific antibodies. We also tested whether an extended, 6-week immunization interval using the same vaccine regimen as in the coadministration group would enhance the quality of antibody responses. We found that pediatric HIV vaccines administered at birth are effective in inducing HIV Env-specific plasma IgG. The vaccine regimen consisting of only HIV Env protein induced the highest levels of variable region 1 and 2 (V1V2)-specific antibodies and tier 1 neutralizing antibodies, whereas the extended-interval regimen induced both persistent Env-specific systemic IgG and mucosal IgA responses. Antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies in plasma were elicited by all vaccine regimens. These data suggest that infant immunizations beginning at birth are effective for the induction of functional HIV Env-specific antibodies that could potentially protect against breast milk transmission of HIV and set the stage for immunity prior to sexual debut.

KEYWORDS:

HIV vaccine; antibody responses; infant rhesus macaque model

PMID:
28814388
PMCID:
PMC5629672
DOI:
10.1128/CVI.00231-17
[Indexed for MEDLINE]
Free PMC Article

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