Heterologous Prime-Boost Regimens with a Recombinant XXXX Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional @entity2858 -Specific T-Cell Responses in Macaques.

@entity1 @entity2858 @entity14848 @entity19 @entity4483 @entity831 @entity4453 @entity790
UNASSIGNED: @entity2858 -specific CD4+ and CD8+ T lymphocytes are important for @entity2858 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/ @entity4453 , Pol/RT, @entity4483 and Gag/ @entity14848 ) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in @entity1 . While replication-incompetent recombinant HIV-1/SIV antigen-expressing @entity1 adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to @entity1 serotypes. Non- @entity1 adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant @entity831 adenovirus type 7 vector expressing clade B Gag, RT and @entity4483 , and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and @entity19 . Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and @entity790 ( @entity19 ) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood @entity2858 -specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4+ T cells. Each regimen induced @entity2858 -specific T-cell responses in systemic/local tissues in @entity19 . This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent @entity831 adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.
