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Published Online: 5 July 2004

Identification of Highly Conserved and Broadly Cross-Reactive HIV Type 1 Cytotoxic T Lymphocyte Epitopes as Candidate Immunogens for Inclusion in Mycobacterium bovis BCG-Vectored HIV Vaccines

Publication: AIDS Research and Human Retroviruses
Volume 16, Issue Number 14


One of the fundamental goals of current strategies to develop an efficacious vaccine for AIDS is the elicitation of cytotoxic T lymphocyte (CTL) reactivities capable of recognizing cells infected with different subtypes of the human immunodeficiency virus type 1 (HIV-1). In efforts to explore new vaccine candidates by the UNAIDS/WHO Vaccine Committee, we review the most recent data concerning CTL epitopes that are conserved among the different HIV-1 subtypes. Moreover, we examine HLA allelic frequencies in several different populations, to determine those that could contribute to the goal of a cumulative phenotype frequency (CP) of at least 80%. By analyzing conserved epitopes in the context of HLA restricting alleles, we define a set of HIV-1 gene regions that may have the greatest potential to induce cross-clade reactive CTLs. The absence of well-defined correlates of immune protection that link CTL epitopes to delayed disease progression and/or prevention of infection does not permit an assignment of rank order of the most relevant component of a candidate vaccine. Thus far, most of the studies conducted in clade B-infected patients to define conserved and immunodominant epitopes indicate gag and pol gene products to be the most conserved among the HIV-1 subtypes. Moreover, anti-Pol and-Gag CTL responses appear to correlate inversely with disease progression, suggesting that they should be among the first choice of antigens to be included in a candidate vaccine construct aimed at induction of broad CTL responses. The impact of a clade B-based vaccine as a worldwide candidate capable of inducing protective immune responses can be determined only after "in vivo" studies. Meanwhile, extensive parallel studies in populations infected with non-clade B HIV-1 subtypes should define the patterns of immunodominant epitopes and HLA for comparison with the data already collected in clade B-infected subjects.

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cover image AIDS Research and Human Retroviruses
AIDS Research and Human Retroviruses
Volume 16Issue Number 14September 2000
Pages: 1433 - 1443
PubMed: 11018863


Published online: 5 July 2004
Published in print: September 2000


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Guido Ferrari
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27707
Donna D. Kostyu
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27707
Josephine Cox
Henry H. Jackson Foundation, Rockville, Maryland
Deborah V. Dawson
Department of Epidemiology and Biostatistics, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio
Jorge Flores
Division of AIDS, NIH/NIAID, Bethesda, Maryland
Kent J. Weinhold
Departments of Surgery and Immunology, Duke University Medical Center, Durham, North Carolina 27707
Saladin Osmanov
Joint United Nations Programme on HIV/AIDS, Geneva, Switzerland

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