Abstract
Cellular immune responses are implicated in resistance to HIV and have been considered for the development of an effective vaccine. Despite their safety profile, subunit vaccines need to be delivered combined with an adjuvant. In the last years, in vivo antigen targeting to dendritic cells (DCs) using chimeric monoclonal antibodies (mAb) against the DC endocytic receptor DEC205/CD205 was shown to support long-term T cell immunity. Here, we evaluated the ability of different adjuvants to modulate specific cellular immune response when eight CD4+ HIV-derived epitopes (HIVBr8) were targeted to DEC205+ DCs in vivo. Immunization with two doses of αDECHIVBr8 mAb along with poly(I:C) induced Th1 cytokine production and higher frequency of HIV-specific polyfunctional and long-lived T cells than MPL or CpG ODN-assisted immunization. Although each adjuvant elicited responses against the 8 epitopes present in the vaccine, the magnitude of the T cell response was higher in the presence of poly(I:C). Moreover, poly(I:C) up regulated the expression of costimulatory molecules in both cDC1 and cDC2 DCs subsets. In summary, the use of poly(I:C) in a vaccine formulation that targets multiple epitopes to the DEC205 receptor improved the potency and the quality of HIV-specific responses when compared to other vaccine-adjuvant formulations. This study highlights the importance of the rational selection of antigen/adjuvant combination to potentiate the desired immune responses.
Highlights
Vaccine induced T cell immunity is required for effective protection against intracellular pathogens responsible for diseases classified as global threats like AIDS, tuberculosis, malaria, and against cancer
To examine the effect of different adjuvants on HIV-specific cellular immune response, mice were immunized with two doses of αDECHIVBr8 monoclonal antibodies (mAb) in the presence of the toll-like receptors (TLRs) agonists poly(I:C), Monophosphoryl lipid A (MPL) or CpG ODN 1826
We observed that 15 days after the boost splenocytes from mice immunized with αDECHIVBr8 mAb combined with poly(I:C) presented higher number of specific IFNγ producing cells (716 SFU/106 cells) when compared to the groups immunized in the presence of MPL or CpG ODN 1826 (404 and 286 SFU/106 cells, respectively)
Summary
Vaccine induced T cell immunity is required for effective protection against intracellular pathogens responsible for diseases classified as global threats like AIDS, tuberculosis, malaria, and against cancer. The ability of dendritic cells (DCs) to uptake, process and present antigens is crucial to induce and regulate T cell immunity [1]. Activation of DCs has been considered key in vaccines designed to induce cellular immunity [2]. Conventional type 1 DCs encompass lymphoid CD8α+ and non-lymphoid CD103+, both of which express DEC205. DEC205 known as CD205 is a C-type lectin endocytic receptor and was the first identified DC-specific receptor [11]. Synthetic CpG oligonucleotides (ODNs), a potent immunostimulator, were identified as ligands that bind to the surface DEC205 [14, 15]
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