Human leukocyte antigen class I haplotypes of human immunodeficiency virus–1–infected persons on Likoma Island, Malawi

Yang, Otto O.; Lewis, Martha; Reed, Elaine F.; Gjertson, David W.; Kalilani-Phiri, Linda; Mkandawire, James; Helleringer, Stéphane; Köhler, Hans Peter

doi:10.1016/j.humimm.2011.05.003

Cited by 3 publications

(2 citation statements)

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“…About 40% of the world is HLA-A2 [27] with between 35–50% in every ethnicity in the USA [28] . In addition, the HLA-A2.1, HLA-B7 and HLA-B35 haplotype associated Pf CSP CD8 + T-cell epitopes have all been associated with protection from malaria in Africans and other ethnic groups [29] – [32] thus a vaccine based on these CD8 + T-cell epitopes should have a broad coverage throughout the world. If the vaccine is tested with a P. falciparum 3D7 clone challenge, all three CD8 epitopes will be present on the CSP of the invading sporozoite.…”

Section: Discussionmentioning

confidence: 99%

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

et al. 2012

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BackgroundThe worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8+ and CD4+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects.Methodology/Principal FindingsTo establish the basis for a SAPN-based vaccine, B- and CD8+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ+, IL-2+) long-lived central memory CD8+ T-cells. Furthermore, we demonstrated that these Ab or CD8+ T–cells can independently provide sterile protection against a lethal challenge of the transgenic parasites.ConclusionThe SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP.

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Section: Discussionmentioning

confidence: 99%

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

et al. 2012

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“…The few studies from southern Africa also highlight the knowledge gap on HLA diversity in this region in this era of high resolution typing. Several HLA disease association studies with allele frequency data have been reported in the region [ 7 , 59 , 93 – 95 ]; these frequencies might not be a true reflection of the general population owing to the confounding effect of the diseases. Allele frequency is highly dependent on sample size and hence might not give a clear picture of HLA diversity.…”

Section: Hla Diversitymentioning

confidence: 99%

Human Leukocyte Antigen Diversity: A Southern African Perspective

Tshabalala

Mellet

Pepper

2015

Journal of Immunology Research

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Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA) diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of transplantation therapeutic interventions. This review highlights the paucity of HLA diversity data amongst southern African populations and defines a need for information of this kind. This information will support disease association studies, provide guidance in vaccine design, and improve transplantation outcomes.

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Cohort Profile: The Likoma Network Study (LNS)

Helleringer

Mkandawire

Kalilani-Phiri

et al. 2013

International Journal of Epidemiology

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The Likoma network study (LNS) investigates the sexual networks connecting the inhabitants of Likoma, a small island of Lake Malawi with high HIV prevalence. Whereas previous studies of sexual networks and HIV/AIDS in sub-Saharan countries have focused solely on the personal networks of a small number of respondents, the LNS attempts to document the sexual networks of the entire adult population of Likoma. To do so, it uses a unique sociocentric study design, in which all members of the local population are contacted for a survey interview and are asked to nominate their five most recent sexual partners. Using these data, quasi-complete 'maps' of the sexual networks connecting inhabitants of the island can be constructed. These maps allow investigation of the impact of networks on HIV epidemiology and can inform mathematical models of HIV prevention. In addition to data on sexual networks, the LNS data include information on the social networks (e.g. friendship), socioeconomic characteristics and HIV status of Likoma's residents. Baseline data were collected in 2005-06. A first follow-up was conducted in 2007-08 and a second follow-up is planned for early 2013. Access to the LNS data is contingent upon review of a short concept paper and forming collaborations with LNS investigators.

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Human leukocyte antigen class I haplotypes of human immunodeficiency virus–1–infected persons on Likoma Island, Malawi

Cited by 3 publications

References 33 publications

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

Human Leukocyte Antigen Diversity: A Southern African Perspective

Cohort Profile: The Likoma Network Study (LNS)

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