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Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.

ABSTRACT: Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

SUBMITTER: Mohamed YS

PROVIDER: S-EPMC7349992 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.

Mohamed Yehia S YS Borthwick Nicola J NJ Moyo Nathifa N Murakoshi Hayato H Akahoshi Tomohiro T Siliquini Francesca F Hannoun Zara Z Crook Alison A Hayes Peter P Fast Patricia E PE Mutua Gaudensia G Jaoko Walter W Silva-Arrieta Sandra S Llano Anuska A Brander Christian C Takiguchi Masafumi M Hanke Tomáš T

Vaccines 20200529 2

Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of ...[more]

PMID: 32485938

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Project description:Background1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as 'advancing research' and collaboration with science, and personal benefits such as health benefits and financial interests.MethodA thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site.ResultsOf the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research.ConclusionThe majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine clinical trials.

Project description:BACKGROUND: It has been almost a decade since HIV was declared a national disaster in Kenya. Antiretroviral therapy (ART) provision has been a mainstay of HIV treatment efforts globally. In Kenya, the government started ART provision in 2003 with significantly scale-up after 2006. This study aims to demonstrate changes in population-level HIV mortality in two high HIV prevalence slums in Nairobi with respect to the initiation and subsequent scale-up of the national ART program. METHODS: We used data from 2070 deaths of people aged 15-54 years that occurred between 2003 and 2010 in a population of about 72,000 individuals living in two slums covered by the Nairobi Urban Health and Demographic Surveillance System. Only deaths for which verbal autopsy was conducted were included in the study. We divided the analysis into two time periods: the "early" period (2003-2006) which coincides with the initiation of ART program in Kenya, and the "late" period (2007-2010) which coincides with the scale up of the program nationally. We calculated the mortality rate per 1000 person years by gender and age for both periods. Poisson regression was used to predict the risk of HIV mortality in the two periods while controlling for age and gender. RESULTS: Overall, HIV mortality declined significantly from 2.5 per 1,000 person years in the early period to 1.7 per 1,000 person years in the late period. The risk of dying from HIV was 53 percent less in the late period compared to the period before, controlling for age and gender. Women experienced a decline in HIV mortality between the two periods that was more than double that of men. At the same time, the risk of non-HIV mortality did not change significantly between the two time periods. CONCLUSIONS: Population-level HIV mortality in Nairobi's slums was significantly lower in the approximate period coinciding with the scale-up of ART provision in Kenya. However, further studies that incorporate ART coverage data in mortality estimates are needed. Such information will enhance our understanding of the full impact of ART scale-up in reducing adult mortality among marginalized slum populations in Kenya.

Dataset Information

Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.

Publications

Specificity of CD8<sup>+</sup> T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya.

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