Conservation of HIV-1 T cell epitopes across time and clades: Validation of immunogenic HLA-A2 epitopes selected for the GAIA HIV vaccine

Abstract

HIV genomic sequence variability has complicated efforts to generate an effective globally relevant vaccine. Regions of the viral genome conserved in sequence and across time may represent the “Achilles’ heel” of HIV. In this study, highly conserved T-cell epitopes were selected using immunoinformatics tools combining HLA-A2 supertype binding predictions with relative global conservation. Analysis performed in 2002 on 10,803 HIV-1 sequences, and again in 2009, on 43,822 sequences, yielded 38 HLA-A2 epitopes. These epitopes were experimentally validated for HLA binding and immunogenicity with PBMCs from HIV-infected patients in Providence, Rhode Island, and/or Bamako, Mali. Thirty-five (92%) stimulated an IFNγ response in PBMCs from at least one subject. Eleven of fourteen peptides (79%) were confirmed as HLA-A2 epitopes in both locations. Validation of these HLA-A2 epitopes conserved across time, clades, and geography supports the hypothesis that such epitopes could provide effective coverage of virus diversity and would be appropriate for inclusion in a globally relevant HIV vaccine.

Low immunogenicity predicted for emerging avian-origin H7N9

“…The above analysis is based on in silico predictions using a well-validated immunoinformatics toolkit 24 . Based on historical performance, we expect these epitope predictions to be 93-99% accurate; in addition, correlations with published H1N1 and H3N2 epitopes are provided in Tables S1 and S2.…”

Universal H1N1 influenza vaccine development

“…We have also developed tools that identify highly cross-conserved CD8 + T cell responses and have validated their accuracy. [33][34][35] Highly efficient algorithms, such as these, may be useful for accelerated development of vaccines against emerging infections in the context of newly emerging infections or bioterror events. 36 An important safety feature of the vaccine design approach described here is that T cell epitopes that have a high degree of cross-conservation with human genome are taken into consideration and eliminated from the list of epitopes to be tested and included in vaccine constructs, as there is at least initial evidence infection slows considerably, beyond the degree seen in the primary response.…”

In silicodesign of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations

“…16 One such strategy is to design a vaccine that targets only the conserved epitopes and aims to induce a broader cross-protective immune response. 17,18 Epitopes are the smallest and most important units that can elicit immune responses. As such, they are potential candidates for modern vaccine design and have unique advantages.…”