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Evolutionarily conserved cytotoxic T-lymphocyte epitopes on the human immunodeficiency virus and the feline immunodeficiency virus for an HIV-1 vaccine

Posted on:2013-05-18Degree:Ph.DType:Dissertation
University:University of FloridaCandidate:Sanou, Missa PatrickFull Text:PDF
GTID:1454390008479541Subject:virology
Abstract/Summary:
The release of a commercial HIV vaccine for a global population is not yet imminent even after close to three decades of research. Most scientists today believe that both humoral and cell-mediated immune (CMI) responses generated by immunization will be important in such a vaccine. Efforts to induce those responses take into account the diversity of the virus, as well as the variability of major histocompatibility complex across the globe, especially when it comes to CMI responses. The CMI responses of HIV-1+ long-term survivors against the conserved regions of the virus have highlighted their importance in the control of the infection. These responses have also indicated a role of polyfunctional cytotoxic T-lymphocytes (CTLs) and CTL inducing-epitopes for an effective HIV-1 vaccine. Furthermore, conserved epitopes were shown to be determinant in an HIV vaccine trial. The most conserved HIV regions are likely to be the best immunogens for inducing protective CTLs, as these epitopes will not easily mutate without an associated fitness cost to the virus. Cross-species recognition has been observed with other viruses and with HIV. The current studies identified conserved regions on HIV by simultaneously comparing the immunological responses of HIV-infected individuals to overlapping peptides from HIV and from the feline immunodeficiency virus (FIV). The reverse transcriptase enzymes and viral core capsid proteins of both HIV and FIV were evaluated for their counterpart conserved CTL epitopes. These studies showed that the proliferation profile of T cells to HIV and FIV may be more useful for the identification of conserved regions than their induction of interferon-gamma secretion. Furthermore, the current approach was able to identify a unique HIV-specific epitope, never described before which is highly conserved among lentiviruses and which has the ability to induce CTL cytokines. Therefore, evolutionarily-conserved HIV CTL epitopes exist and can be mapped by comparing the immunological responses of HIV-infected subjects to the conserved proteins between HIV and FIV, and possibly other lentiviruses.
Keywords/Search Tags:Conserved, Vaccine, Feline immunodeficiency virus, Epitopes, Responses
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