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Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses


Attempts to develop an HIV vaccine that elicits potent cell-mediated immunity have so far been unsuccessful. This is due in part to the use of immunogens that appear to recapitulate responses induced naturally by HIV that are, at best, partially effective. We previously showed that the capacity of CD8+ T cells from patients to block HIV replication in culture is strongly correlated with HIV control in vivo, therefore, we investigated the virological determinants of potent CD8+ T cell inhibitory activity. We observed that CD8+ T cells from patients with naturally low plasma viral loads (viremic controllers) were better able to inhibit the replication of diverse HIV strains in vitro than CD8+ T cells from HIV-noncontroller patients. Importantly, we also found that the potency of the antiviral activity in the latter group was strongly correlated with recognition of selected regions across the viral proteome that are critical to viral fitness. Vaccines that encode full-length viral proteins rarely elicited responses to these vulnerable regions. Taken together, our results provide insight into the characteristics of effective cell-mediated immune responses against HIV and how these may inform the design of better immunogens.


Vyšlo v časopise: Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004658
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004658

Souhrn

Attempts to develop an HIV vaccine that elicits potent cell-mediated immunity have so far been unsuccessful. This is due in part to the use of immunogens that appear to recapitulate responses induced naturally by HIV that are, at best, partially effective. We previously showed that the capacity of CD8+ T cells from patients to block HIV replication in culture is strongly correlated with HIV control in vivo, therefore, we investigated the virological determinants of potent CD8+ T cell inhibitory activity. We observed that CD8+ T cells from patients with naturally low plasma viral loads (viremic controllers) were better able to inhibit the replication of diverse HIV strains in vitro than CD8+ T cells from HIV-noncontroller patients. Importantly, we also found that the potency of the antiviral activity in the latter group was strongly correlated with recognition of selected regions across the viral proteome that are critical to viral fitness. Vaccines that encode full-length viral proteins rarely elicited responses to these vulnerable regions. Taken together, our results provide insight into the characteristics of effective cell-mediated immune responses against HIV and how these may inform the design of better immunogens.


Zdroje

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