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

Vaccine. 2013 Feb 4;31(7):1106-12. doi: 10.1016/j.vaccine.2012.12.023. Epub 2012 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil
  • Cross Reactions
  • Enzyme-Linked Immunospot Assay
  • Genotype
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Interferon-gamma / metabolism*
  • T-Lymphocytes / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / immunology*
  • nef Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • gag Gene Products, Human Immunodeficiency Virus
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • Interferon-gamma