Striking lack of T cell immunodominance in both a multiclade and monoclade HIV-1 epidemic: implications for vaccine development
| Autor: | Surita Roux, Marcel Tongo, Lycias Zembe, Eitel Mpoudi-Ngole, Linda-Gail Bekker, Wendy A. Burgers, Carolyn Williamson, Eugenie Ebong |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male T cell T-Lymphocytes Human immunodeficiency virus (HIV) HIV Infections Immunodominance Biology medicine.disease_cause gag Gene Products Human Immunodeficiency Virus Epitope South Africa Young Adult medicine Humans Amino Acid Sequence Cameroon nef Gene Products Human Immunodeficiency Virus HIV vaccine Clade AIDS Vaccines General Veterinary General Immunology and Microbiology Immunodominant Epitopes ELISPOT Public Health Environmental and Occupational Health virus diseases Middle Aged Virology Infectious Diseases medicine.anatomical_structure Homogeneous HIV-1 Molecular Medicine Female |
| Zdroj: | Vaccine. 32(20) |
| ISSN: | 1873-2518 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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