Comprehensive epitope analysis of cross-clade Gag-specific T-cell responses in individuals with early HIV-1 infection in the US epidemic

Malhotra, Uma; Nolin, Jessica; Mullins, James I.; McElrath, M. Juliana

doi:10.1016/j.vaccine.2006.07.045

Cited by 24 publications

(18 citation statements)

References 46 publications

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“…We had limited ability to confirm responses using frozen samples due to limited numbers of PBMC. Stimulating peptide pools spanned the subtype A genome, and it is possible that a lack of cross-subtype reactivity resulted in lower response rates among those exposed to non-A subtypes; however, clade A accounts for Ͼ70% of HIV-1 infections in Kenya, and there is strong evidence of cross-clade ELISpot reactivity (3,13,20,29,33,35,52,53). Finally, assays were performed in an unblinded manner.…”

Section: Discussionmentioning

confidence: 99%

HIV-1-Specific Enzyme-Linked Immunosorbent Spot Assay Responses in HIV-1-Exposed Uninfected Partners in Discordant Relationships Compared to Those in Low-Risk Controls

Guthrie

Lohman-Payne

Liu

et al. 2012

Clin. Vaccine Immunol.

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Section: Discussionmentioning

confidence: 99%

HIV-1-Specific Enzyme-Linked Immunosorbent Spot Assay Responses in HIV-1-Exposed Uninfected Partners in Discordant Relationships Compared to Those in Low-Risk Controls

Guthrie

Lohman-Payne

Liu

et al. 2012

Clin. Vaccine Immunol.

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“…Lately, studies have shown that a broad cross-recognition is associated with a slower disease progression and a better control of the virus (6, 7). Also, the high mutation rate of HIV-1 makes it impossible to identify CTL epitopes that are conserved among all subtypes, which is why the identification of cross-reactive between-clade T cell responses would be important to achieve in vaccine models (23,24). In our study, we successfully identified several broadly immunogenic elite epitopes, including six with sequence variants recognized in a diverse patient population, which constitute promising candidates for vaccine-induced cellular immune responses.…”

Section: Discussionmentioning

confidence: 99%

Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes

Pérez

Larsen

Gustafsson

et al. 2008

The Journal of Immunology

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The genetic variations of the HIV-1 virus and its human host constitute major obstacles for obtaining potent HIV-1-specific CTL responses in individuals of diverse ethnic backgrounds infected with different HIV-1 variants. In this study, we developed and used a novel algorithm to select 184 predicted epitopes representing seven different HLA class I supertypes that together constitute a broad coverage of the different HIV-1 strains as well as the human HLA alleles. Of the tested 184 HLA class I-restricted epitopes, 114 were recognized by at least one study subject, and 45 were novel epitopes, not previously described in the HIV-1 immunology database. In addition, we identified 21 "elite" epitopes that induced CTL responses in at least 4 of the 31 patients. A majority (27 of 31) of the study population recognized one or more of these highly immunogenic epitopes. We also found a limited set of 9 epitopes that together induced HIV-1-specific CTL responses in all HIV-1-responsive patients in this study. Our results have important implications for the validation of potent CTL responses and show that the goal for a vaccine candidate in inducing broadly reactive CTL immune responses is attainable.

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“…Here, we demonstrated that there exist significant differences in the quality (cytokine secretion profile and cytotoxic activity) and magnitude of the CD8 response to different epitope variants. Significant differences in the avidity of the T-cell responses (46), which can influence the cytokine response profiles (40,52) and cytotoxic activity of CD8 ϩ T cells (31), were demonstrated to have an important impact on virus control. Taken together, these data will help discern the best antigens to be included in future HIV vaccines that induce T-cell populations with optimal effector functions.…”

Section: Discussionmentioning

confidence: 99%

“…Results were expressed as spotforming units (SFU)/10 6 PBMCs after subtraction of the negative-control values. Thresholds for positive responses for the test wells were defined as at least 50 SFU/10 6 PBMCs or as mean SFU greater than three times the mean SFU of the negative-control wells, whichever was higher (19,36,45,46). Confirmation of individual peptide responses was performed in triplicate.…”

mentioning

confidence: 99%

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Turk

Gherardi

Laufer

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTLs) arising during the acute phase of infection are associated with containment of viral replication and resolution of acute-phase symptoms (5,13,14,44). Detailed characterization of these cell populations and viral immunodominant epitopes will provide key data for developing and enhancing immunization strategies. In this sense, one major challenge is HIV variability, characterized by substantial inter-and intraclade sequence diversity. To date, most reports aimed at studying CTL responses are focused on HIV clade Band C-infected patients. In Argentina, epidemiological studies revealed that early predominance of B subtype has been overshadowed by the emergence of BF recombinants (16,23,32,33,53). These reports indicate that near 50% of the HIVinfected people living in Argentina are infected either with the circulating recombinant form CRF12_BF or other BF recombinant forms related to CRF12_BF. Moreover, in other South American countries, such as Brazil and Uruguay, high prevalence of F subtype and BF recombinant variants are also found (16,32,34). These findings provide an adequate scenario to fill the gap concerning fine mapping of CTL responses in nonclade B-and C-infected patients.Cross-clade CTL responses were studied by different groups using different approaches. The first publications used vaccinia virus-based constructs or peptide pools as stimulating factors (2,19,20,27). Not until recently was fine mapping of these responses achieved by using individual peptides based on different subtypes (22,28). The latter allows for a more detailed and comprehensive understanding of cross-clade reactive populations.Here, cross-clade and clade-specific T-cell responses in Band BF-infected patients from Argentina are reported. These assays were performed shortly after seroconversion in order to avoid the confounders associated with viral diversification, selection of escape mutants, and superinfection. Overlapping peptides spanning the Nef protein were chosen as antigens because of the following: (i) Nef is halfway along the spectrum of variability found in HIV proteins; (ii) during primary HIV infection, Nef-specific CTLs represent between 46% and 94% of the total magnitude of the HIV T-cell response (43); (iii) Nef has, together with Gag, the highest epitope density (1,39). This study also contributes to minimizing the problem of breadth underestimation during CTL screening and provides insights into discrepancies of CD8 T-cell effector function.

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Comprehensive epitope analysis of cross-clade Gag-specific T-cell responses in individuals with early HIV-1 infection in the US epidemic

Cited by 24 publications

References 46 publications

HIV-1-Specific Enzyme-Linked Immunosorbent Spot Assay Responses in HIV-1-Exposed Uninfected Partners in Discordant Relationships Compared to Those in Low-Risk Controls

HIV-1-Specific Enzyme-Linked Immunosorbent Spot Assay Responses in HIV-1-Exposed Uninfected Partners in Discordant Relationships Compared to Those in Low-Risk Controls

Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

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