Dataset Information

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity.

ABSTRACT: Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24?h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30?h, or a 21-day triple-drug ART regimen at 48?h, are aviremic with almost no virus in tissues. In contrast, bNAb treatment beginning at 48?h leads to tight control without adaptive immune responses in half of animals. We conclude that both bNAbs and ART mediate effective post-exposure prophylaxis in infant macaques within 30-48?h of oral SHIV exposure. Our findings suggest that optimizing the treatment regimen may extend the window of opportunity for preventing perinatal HIV infection when treatment is delayed.

SUBMITTER: Shapiro MB

PROVIDER: S-EPMC6946664 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity.

Shapiro Mariya B MB Cheever Tracy T Malherbe Delphine C DC Pandey Shilpi S Reed Jason J Yang Eun Sung ES Wang Keyun K Pegu Amarendra A Chen Xuejun X Siess Don D Burke David D Henderson Heidi H Lewinsohn Rebecca R Fischer Miranda M Stanton Jeffrey J JJ Axthelm Michael K MK Kahl Christoph C Park Byung B Lewis Anne D AD Sacha Jonah B JB Mascola John R JR Hessell Ann J AJ Haigwood Nancy L NL

Nature communications 20200107 1

Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug AR ...[more]

PMID: 31911610

Similar Datasets

Project description:We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVBG505 DNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally. Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIVBG505 Env. Group 2 was boosted with a SHIVBG505-OPV vaccine including a non-secreting SIVmac239CA-p6-OPV, expressing Gag CA, NC and p6 proteins, and a HIVBG505C1-V2-OPV, secreting the C1-V2 fragment of HIV EnvBG505, recognized by the broadly neutralizing antibody PG16. A time course analysis of anti-SHIV Gag and Env CD4+ and CD8+ T-cell responses in PBMC and in lymph node, rectal, and vaginal MNC was carried out. Both regimens stimulated significant cell-mediated responses in all compartments, with SHIVBG505-OPV immunization stimulating more significant levels of responses than rMVA- SHIVBG505. Boolean analysis of these responses revealed predominantly monofunctional responses with multifunctional responses also present in all tissues. Stimulation of antibody responses was disappointing in both groups with negative anti-SHIV IgG in plasma, and IgA in salivary, rectal and vaginal secretions being restricted to a few animals. After repeated rectal challenge with SHIVBG505, two Group 1 animals remained uninfected at challenge termination. No significant differences were observed in post-infection viral loads between groups. After the acute phase decline, CD4+ T cell percentages returned to normal levels in vaccinated as well as control animals. However, when compared to controls, vaccinate groups had more significant preservation of PBMC and rectal MNC Th17/Treg ratios, considered the strongest surrogate marker of progression to AIDS. We conclude that the vaccine platforms used in this study are insufficient to stimulate significant humoral immunity at the tested doses and schedule but sufficient to stimulate significant mucosal and systemic cell-mediated immunity, impacting the preservation of key Th17 CD4+ T cells in blood and rectal mucosa.

Dataset Information

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity.

Publications

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets