Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

Author(s)

Vinicius Canato Santana ; Rafael Ribeiro Almeida ; Susan Pereira Ribeiro ; Luís Carlos de Souza Ferreira ^[4] ; Jorge Kalil ; Daniela Santoro Rosa ; Edecio Cunha Neto

• Document type: Journal article
• Source: Memórias do Instituto Oswaldo Cruz; v. 110, n. 8, p. 1010-1016, 2015-11-24.

Abstract

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. (AU)

• FAPESP's process: 06/50096-0 - Characterization of Human Immunodeficiency Virus type 1 (HIV-1) in a cohort of recently infected persons from the State of São Paulo by full genome sequencing
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/57881-0 - Institute for Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• Support Opportunities: Research Projects - Thematic Grants