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Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

ABSTRACT: One of the most successful HIV vaccines to date, the RV144 vaccine tested in Thailand, demonstrated correlates of protection including cross-clade V1V2 immunoglobulin G (IgG) breadth, Env-specific CD4+ T cell polyfunctionality, and antibody-dependent cellular cytotoxicity (ADCC) in vaccinees with low IgA binding. The HIV Vaccine Trials Network (HVTN) 097 trial evaluated this vaccine regimen in South Africa, where clade C HIV-1 predominates. We compared cellular and humoral responses at peak and durability immunogenicity time points in HVTN 097 and RV144 vaccinee samples, and evaluated vaccine-matched and cross-clade immune responses. At peak immunogenicity, HVTN 097 vaccinees exhibited significantly higher cellular and humoral immune responses than RV144 vaccinees. CD4+ T cell responses were more frequent in HVTN 097 irrespective of age and sex, and CD4+ T cell Env-specific functionality scores were higher in HVTN 097. Env-specific CD40L+ CD4+ T cells were more common in HVTN 097, with individuals having this pattern of expression demonstrating higher median antibody responses to HIV-1 Env. IgG and IgG3 binding antibody rates and response magnitude to gp120 vaccine- and V1V2 vaccine-matched antigens were higher or comparable in HVTN 097 than in RV144 ADCC, and ADCP functional antibody responses were elicited in HVTN 097. Env-specific IgG and CD4+ Env responses declined significantly over time in both trials. Overall, cross-clade immune responses associated with protection were better than expected in South Africa, suggesting wider applicability of this regimen.

SUBMITTER: Gray GE

PROVIDER: S-EPMC7199879 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

Gray Glenda E GE Huang Ying Y Grunenberg Nicole N Laher Fatima F Roux Surita S Andersen-Nissen Erica E De Rosa Stephen C SC Flach Britta B Randhawa April K AK Jensen Ryan R Swann Edith M EM Bekker Linda-Gail LG Innes Craig C Lazarus Erica E Morris Lynn L Mkhize Nonhlanhla N NN Ferrari Guido G Montefiori David C DC Shen Xiaoying X Sawant Sheetal S Yates Nicole N Hural John J Isaacs Abby A Phogat Sanjay S DiazGranados Carlos A CA Lee Carter C Sinangil Faruk F Michael Nelson L NL Robb Merlin L ML Kublin James G JG Gilbert Peter B PB McElrath M Juliana MJ Tomaras Georgia D GD Corey Lawrence L

Science translational medicine 20190901 510

One of the most successful HIV vaccines to date, the RV144 vaccine tested in Thailand, demonstrated correlates of protection including cross-clade V1V2 immunoglobulin G (IgG) breadth, Env-specific CD4<sup>+</sup> T cell polyfunctionality, and antibody-dependent cellular cytotoxicity (ADCC) in vaccinees with low IgA binding. The HIV Vaccine Trials Network (HVTN) 097 trial evaluated this vaccine regimen in South Africa, where clade C HIV-1 predominates. We compared cellular and humoral responses a ...[more]

PMID: 31534016

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Project description:BACKGROUND:RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individual-based network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective. METHODS:Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24?months after the first dose and include two-yearly boosters that maintain durable efficacy over 10?years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions. RESULTS:Our analysis shows that this partially effective vaccine could prevent, at catch-up vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750). CONCLUSIONS:While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.

Dataset Information

Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

Publications

Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa.

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