Show simple item record

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.

dc.contributor.author Bay, CP
dc.contributor.author De Paris, K
dc.contributor.author Dennis, ML
dc.contributor.author Eudailey, Josh
dc.contributor.author Ferrari, Guido
dc.contributor.author Fouda, Genevieve
dc.contributor.author Hudgens, MG
dc.contributor.author Huffman, TN
dc.contributor.author Kozlowski, PA
dc.contributor.author Parker, ME
dc.contributor.author Permar, Sallie R
dc.contributor.author Phillips, BL
dc.contributor.author Pickup, DJ
dc.contributor.author Pollara, Justin Joseph
dc.contributor.author Van Rompay, KKA
dc.contributor.author Wiseman, RW
dc.coverage.spatial United States
dc.date.accessioned 2018-02-01T15:01:10Z
dc.date.available 2018-02-01T15:01:10Z
dc.date.issued 2018-01
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/29359183
dc.identifier mSphere00505-17
dc.identifier.uri https://hdl.handle.net/10161/16037
dc.description.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.
dc.language eng
dc.relation.ispartof mSphere
dc.relation.isversionof 10.1128/mSphere.00505-17
dc.subject HIV-1
dc.subject breast milk
dc.subject maternal vaccination
dc.subject oral challenge
dc.subject placental transfer
dc.subject transmission
dc.title Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/29359183
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Global Health Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 3
dc.identifier.eissn 2379-5042


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record