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HIV-specific CD8+ T cells are known to play a key role in viral control during acute and chronic HIV infection. Although many studies have demonstrated the importance of HIV-specific CD8+ T cells in viral control, its correlation with protection against HIV infection remains incompletely understood. To better understand the nature of the immune response that contributes to the early control of HIV infection, we analyzed the phenotype, distribution and function of anti-viral CD8+ T cells in a cohort of HIV-exposed seronegative (HESN) women, and compared them with healthy controls and HIV-infected individuals. Further, we evaluated the in vitro viral inhibition activity of CD8+ T cells against diverse HIV-1 strains. We found that the HESN group had significantly higher levels of CD8+ T cells that express T-stem cell-like (TSCM) and follicular homing (CXCR5+) phenotype with more effector like characteristics as compared to healthy controls. Further, we observed that the HESN population had a higher frequency of HIV-specific poly-functional CD8+ T cells with robust in vitro virus inhibiting capacity against different clades of HIV. Overall, our results demonstrate that the HESN population has elevated levels of HIV-specific poly-functional CD8+ T cells with robust virus inhibiting ability and express elevated levels of markers pertaining to TSCM and follicular homing phenotype. These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8+ T cell subsets.

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.

HIV-specific CD8+ T cells are known to play a key role in viral control during acute and chronic HIV infection. Although many studies have demonstrated the importance of HIV-specific CD8+ T cells in viral control, its correlation with protection against HIV infection remains incompletely understood. To better understand the nature of the immune response that contributes to the early control of HIV infection, we analyzed the phenotype, distribution and function of anti-viral CD8+ T cells in a cohort of HIV-exposed seronegative (HESN) women, and compared them with healthy controls and HIV-infected individuals. Further, we evaluated the in vitro viral inhibition activity of CD8+ T cells against diverse HIV-1 strains. We found that the HESN group had significantly higher levels of CD8+ T cells that express T-stem cell-like (TSCM) and follicular homing (CXCR5+) phenotype with more effector like characteristics as compared to healthy controls. Further, we observed that the HESN population had a higher frequency of HIV-specific poly-functional CD8+ T cells with robust in vitro virus inhibiting capacity against different clades of HIV. Overall, our results demonstrate that the HESN population has elevated levels of HIV-specific poly-functional CD8+ T cells with robust virus inhibiting ability and express elevated levels of markers pertaining to TSCM and follicular homing phenotype. These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8+ T cell subsets. [ABSTRACT FROM AUTHOR]

T cells play an important role in controlling viral replication during HIV infection. An effective vaccine should, therefore, lead to the induction of a strong and early viral-specific CD8+ T cell response. While polyfunctional T cell responses are thought to be important contributors to the antiviral response, there is evidence to show that polyfunctional HIV- specific CD8+ T cells are just a small fraction of the total HIV-specific CD8+ T cells and may be absent in many individuals who control HIV replication, suggesting that other HIV-1 specific CD8+ effector T cell subsets may be key players in HIV control. Stem cell-like memory T cells (TSCM) are a subset of T cells with a long half-life and self-renewal capacity. They serve as key reservoirs for HIV and contribute a significant barrier to HIV eradication. The present study evaluated vaccine-induced antiviral responses and TSCM cells in volunteers vaccinated with a subtype C prophylactic HIV-1 vaccine candidate administered in a prime-boost regimen. We found that ADVAX DNA prime followed by MVA boost induced significantly more peripheral CD8+ TSCM cells and higher levels of CD8+ T cell-mediated inhibition of replication of different HIV-1 clades as compared to MVA alone and placebo. These findings are novel and provide encouraging evidence to demonstrate the induction of TSCM and cytotoxic immune responses by a subtype C HIV-1 prophylactic vaccine administered using a prime-boost strategy. [ABSTRACT FROM AUTHOR]

Effective vaccine design relies on accurate knowledge of protection against a pathogen, so as to be able to induce relevant and effective protective responses against it. An ideal Human Immunodeficiency virus (HIV) vaccine should induce humoral as well as cellular immune responses to prevent initial infection of host cells or limit early events of viral dissemination. A Phase I HIV-1 prophylactic vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009.The trial tested a HIV-1 subtype C vaccine in a prime-boost regimen, comprising of a DNA prime (ADVAX) and Modified Vaccine Ankara (MVA) (TBC-M4) boost. The trial reported that the vaccine regimen was safe, well tolerated, and resulted in enhancement of HIV-specific immune responses. However, preliminary immunological studies were limited to vaccine-induced IFN-γ responses against the Env and Gag peptides. The present study is a retrospective study to characterize in detail the nature of the vaccine-induced cell mediated immune responses among volunteers, using Peripheral Blood Mononuclear Cells (PBMC) that were archived during the trial. ELISpot was used to measure IFN-γ responses and polyfunctional T cells were analyzed by intracellular multicolor flow cytometry. It was observed that DNA priming and MVA boosting induced Env and Gag specific bi-functional and multi-functional CD4+ and CD8+ T cells expressing IFN-γ, TNF-α and IL-2. The heterologous prime-boost regimen appeared to be slightly superior to the homologous prime-boost regimen in inducing favorable cell mediated immune responses. These results suggest that an in-depth analysis of vaccine-induced cellular immune response can aid in the identification of correlates of an effective immunogenic response, and inform future design of HIV vaccines. [ABSTRACT FROM AUTHOR]

HIV-specific CD8 + T cells are known to play a key role in viral control during acute and chronic HIV infection. Although many studies have demonstrated the importance of HIV-specific CD8 + T cells in viral control, its correlation with protection against HIV infection remains incompletely understood. To better understand the nature of the immune response that contributes to the early control of HIV infection, we analyzed the phenotype, distribution and function of anti-viral CD8 + T cells in a cohort of HIV-exposed seronegative (HESN) women, and compared them with healthy controls and HIV-infected individuals. Further, we evaluated the in vitro viral inhibition activity of CD8 + T cells against diverse HIV-1 strains. We found that the HESN group had significantly higher levels of CD8 + T cells that express T-stem cell-like (TSCM) and follicular homing (CXCR5 + ) phenotype with more effector like characteristics as compared to healthy controls. Further, we observed that the HESN population had a higher frequency of HIV-specific poly-functional CD8 + T cells with robust in vitro virus inhibiting capacity against different clades of HIV. Overall, our results demonstrate that the HESN population has elevated levels of HIV-specific poly-functional CD8 + T cells with robust virus inhibiting ability and express elevated levels of markers pertaining to TSCM and follicular homing phenotype. These results demonstrate that future vaccine and therapeutic strategies should focus on eliciting these critical CD8 + T cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Munusamy Ponnan, Thiruvengadam, Kathirvel, Shankar, Rajaraman, Mathaiyan, Dinesha, Poongulali, Saravanan, Murugavel, Swaminathan, Tripathy, Neogi, Velu and Hanna.)