Poly(I:C) Potentiates T Cell Immunity to a Dendritic Cell Targeted HIV-Multiepitope Vaccine

Author(s)

Apostolico, Juliana de Souza ^{[1, 2]} ; Santos Lunardelli, Victoria Alves ^{[1, 2]} ; Yamamoto, Marcio Massao ^[3] ; Cunha-Neto, Edecio ^{[1, 4]} ; Boscardin, Silvia Beatriz ^{[3, 1]} ; Rosa, Daniela Santoro ^{[1, 2]}

Affiliation

^[1] Inst Invest Immunol Iii INCT, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Lab Expt Vaccines, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 10, APR 24 2019.
• Web of Science Citations: 1

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 alpha DECHIVBr8 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. (AU)

• FAPESP's process: 17/17471-7 - Antigenicity and immunogenicity of Zika virus envelope recombinant proteins
• Grantee: Daniela Santoro Rosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50631-0 - Imaging and improvement of immune protection against malaria parasites
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants