Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.
Abstract
Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1)
contributes to an estimated 150,000 new infections annually. Maternal vaccination
has proven safe and effective at mitigating the impact of other neonatal pathogens
and is one avenue toward generating the potentially protective immune responses necessary
to inhibit HIV-1 infection of infants through breastfeeding. In the present study,
we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia
virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost
administered during pregnancy and postpartum to confer passive protection on infant
rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency
virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting
a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA
responses, the maternal vaccine did not have a discernible impact on infant oral SHIV
acquisition. This study revealed considerable variation in vaccine-elicited IgG placental
transfer and a swift decline of both Env-specific antibodies (Abs) and functional
Ab responses in the infants prior to the first challenge, illustrating the importance
of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly,
the strongest correlation to the number of challenges required to infect the infants
was the percentage of activated CD4+ T cells in the infant peripheral blood at the
time of the first challenge. These findings suggest that, in addition to maternal
immunization, interventions that limit the activation of target cells that contribute
to susceptibility to oral HIV-1 acquisition independently of vaccination may be required
to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies
to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants
will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque
dam-and-infant pairs is the first preclinical study to investigate the protective
role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited
breast milk antibody responses in infant oral virus acquisition. It revealed highly
variable placental transfer of potentially protective antibodies and emphasized the
importance of pregnancy immunization timing to reach peak antibody levels prior to
delivery. While there was no discernible impact of maternal immunization on late infant
oral virus acquisition, we observed a strong correlation between the percentage of
activated CD4+ T cells in infant peripheral blood and a reduced number of challenges
to infection. This finding highlights an important consideration for future studies
evaluating alternative strategies to further reduce the vertical HIV-1 transmission
risk.
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https://hdl.handle.net/10161/16037Published Version (Please cite this version)
10.1128/mSphere.00505-17Publication Info
Eudailey, Joshua A; Dennis, Maria L; Parker, Morgan E; Phillips, Bonnie L; Huffman,
Tori N; Bay, Camden P; ... Permar, Sallie R (2018). Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral
SHIV Acquisition in Infant Macaques. mSphere, 3(1). 10.1128/mSphere.00505-17. Retrieved from https://hdl.handle.net/10161/16037.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Guido Ferrari
Professor in Surgery
The activities of the Ferrari Laboratory are based on both independent basic research
and immune monitoring studies. The research revolves around three main areas of interest:
class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity
(ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With
continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation
along with many other productive collaborations wi
Genevieve Giny Fouda
Associate Professor in Pediatrics
Dr Fouda's research interest is in understanding infant immune responses in the setting
of infection and vaccination. Her current work focuses on HIV mother to child transmission.
Sallie Robey Permar
Adjunct Professor in the Department of Pathology
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission
of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS
to characterize the virus-specific immune responses and virus evolution in breast
milk and develop a maternal vaccine regimen for protection against breast milk transmission
of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific
immune responses and virus evolution in vertically-transmitting an
David James Pickup
Associate Professor Emeritus of Molecular Genetics and Microbiology
Viral inhibition of host immune defensesMany viruses have evolved mechanisms to protect
themselves from host immune defenses. Among this group are the orthopoxviruses, whose
members include smallpox virus, one of the deadliest of human viruses, and cowpox
virus, the virus that Edward Jenner used to begin the eradication of smallpox.One
of the especially interesting features of theses viruses is their ability to interfere
with a wide range of innate and adaptive
Justin Joseph Pollara
Associate Professor in Surgery
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