title: Striking lack of T cell immunodominance in both a multiclade and monoclade HIV-1 epidemic: implications for vaccine development.
abstract: Understanding the impact of HIV diversity on immunological responses to candidate immunogens is critical for HIV vaccine development. We investigated the reactivity and immunodominance patterns of HIV-1 consensus group M Gag and Nef in (i) Cameroon, where individuals infected with the predominant CRF02_AG clade were compared with those infected with diverse non-CRF02_AG clades; and (ii) in a multiclade epidemic, namely Cameroon, compared with a monoclade C epidemic, South Africa. We analyzed 57 HIV-infected individuals from Cameroon and 44 HIV-infected individuals from South Africa for differences in detecting HIV-1 consensus M Gag and Nef T cell responses using the IFN-γ ELISpot assay. We found no difference in the predicted epitope coverage between CRF02_AG and non-CRF02_AG viruses for either Gag or Nef. There were no differences in the magnitude and breadth of responses for CRF02_AG and non-CRF02_AG-infected individuals. In contrast, the specificity of epitope targeting was markedly different between the two groups, with fewer than one third (11/38) of peptides commonly recognized in Gag. Furthermore, only one peptide was commonly recognized by at least three individuals from both AG and non-AG groups, indicating poor immunodominance. For Nef, more than half of all targeted peptides (14/27) were recognized by both groups, and four peptides were commonly targeted by at least three individuals. Three times more peptides were exclusively targeted in the diverse non-CRF02_AG group compared to the CRF02_AG group (10 vs. 3). Of note, similar results were obtained when South Africa, a monoclade C epidemic, and Cameroon, a multiclade epidemic, were compared. The central nature of HIV-1 consensus M sequences resulted in their broad recognition, but failed to identify highly immunodominant peptides between homogeneous and diverse HIV epidemics.
authors.affiliation: Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Institute of Medical Research and Study of Medicinal Plants, Yaoundé, Cameroon.
authors.forename: Marcel
authors.initials: M
authors.lastname: Tongo
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Lycias
authors.initials: L
authors.lastname: Zembe
authors.affiliation: Institute of Medical Research and Study of Medicinal Plants, Yaoundé, Cameroon.
authors.forename: Eugenie
authors.initials: E
authors.lastname: Ebong
authors.affiliation: The Desmond Tutu HIV Centre, Cape Town, South Africa.
authors.forename: Surita
authors.initials: S
authors.lastname: Roux
authors.affiliation: The Desmond Tutu HIV Centre, Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Institute of Medical Research and Study of Medicinal Plants, Yaoundé, Cameroon.
authors.forename: Eitel
authors.initials: E
authors.lastname: Mpoudi-Ngole
authors.affiliation: Division of Medical Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. Electronic address: wendy.burgers@uct.ac.za.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Burgers
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D002163:Cameroon; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013019:South Africa; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016056:Immunodominant Epitopes; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus
keywords: Cameroon; HIV-1 diversity; HIV-1 vaccine; Immunodominance; Monoclade; Multiclade; T cell responses