title: Higher cross-subtype IFN-γ ELISpot responses to Gag and Nef peptides in Brazilian HIV-1 subtype B- and F1- than in C-infected subjects.
abstract: HIV-1 diversity has been considered a huge challenge for the HIV-1 vaccine development. To overcome it, immunogens based on centralized sequences, as consensus, have been tested. In Brazil, the co-circulation of three subtypes offers a suitable scenario to test T cell cross-subtype responses to consensus sequences. Furthermore, we included peptides based on closest viral isolates (CVI) from each subtype analyzed to compare with T cell responses detected against the consensus sequences. The study included 32 subjects infected with HIV-1 subtype B (n=13),C (n=11), and F1 (n=8). Gag and Nef-specific T cell responses were evaluated by IFN-γ-ELISpot assay. Peptides based on CVI sequences were similar to consensus in both reducing genetic distance and detecting T cell responses. A high cross-subtype response between B and F1 in both regions was observed in HIV-1 subtype B and F1-infected subjects. We also found no significant difference in responses to subtype B and C consensus peptides among subtype B-infected subjects. In contrast, the magnitude of T cell responses to consensus C peptides in the Gag region was higher than to consensus B peptides among HIV-1 subtype C-infected subjects. Regarding Nef, subtype C-infected subjects showed higher values to consensus C than to consensus F1 peptides. Moreover, subtype F1-infected subjects presented lower responses to subtype C peptides than to subtype F1 and B. A similar level of responses was detected with group M based peptides in subtype B and F1 infected subjects. However, among subtype C infected subjects, this set of peptides detected lower levels of response than consensus C. Overall, the level of cross-subtype response between subtypes B and F1 was higher than between subtype C and B or C and F1. Our data suggests that the barrier of genetic diversity in HIV-1 group M for vaccine design may be dependent on the subtypes involved.
authors.affiliation: Laboratório de Aids e Imunologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ 21040-360, Brazil.
authors.forename: Fernanda Heloise
authors.initials: FH
authors.lastname: Côrtes
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Bello
authors.forename: Carla
authors.initials: C
authors.lastname: Vorsatz
authors.forename: José Henrique
authors.initials: JH
authors.lastname: Pilotto
authors.forename: Monick Lindenmeyer
authors.initials: ML
authors.lastname: Guimarães
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Valdiléa Gonçalves
authors.initials: VG
authors.lastname: Veloso
authors.forename: Aguinaldo Roberto
authors.initials: AR
authors.lastname: Pinto
authors.forename: Mariza Gonçalves
authors.initials: MG
authors.lastname: Morgado
mesh_terms: D001938:Brazil; D003429:Cross Reactions; D058501:Enzyme-Linked Immunospot Assay; D005838:Genotype; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D007371:Interferon-gamma