Multiple Approaches for Increasing the Immunogenicity of an Epitope-Based Anti-HIV Vaccine

Abstract

The development of a highly effective vaccine against the human immunodeficiency virus (HIV) will likely be based on rational vaccine design, since traditional vaccine approaches have failed so far. In recent years, an understanding of what type of immune response is protective against infection and/or disease facilitated vaccine design. T cell-based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. In this context, CD4(+) T cells play a direct cytotoxic role and are also important for the generation and maintenance of functional CD8(+) T and B cell responses. The use of MHC-binding algorithms has allowed the identification of novel CD4(+) T cell epitopes that could be used in vaccine design, the so-called epitope-driven vaccine design. Epitope-based vaccines have the ability to focus the immune response on highly antigenic, conserved epitopes that are fully recognized by the target population. We have recently mapped a set of conserved multiple HLA-DR-binding HIV-1 CD4 epitopes and observed interferon (IFN)-γ-producing CD4(+) T cells when we tested these peptides in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals. We then designed multiepitopic DNA vaccines that induced broad and polyfunctional T cell responses in immunized mice. In this review we will focus on alternative strategies to increase the immunogenicity of an epitope-based vaccine against HIV infection.

Propionibacterium acnes Enhances the Immunogenicity of HIVBr18 Human Immunodeficiency Virus-1 Vaccine

“…A DNA vaccine, such as HIVBr18 vaccine, can induce a potent and persistent response of CD4 + T cells with a polyfunctional phenotype and thus can facilitate the cytotoxic activity of these cells. As previously shown in the literature, this type of DNA vaccine may have a protective effect against SIV/HIV infection ( 15 , 18 , 19 , 22 , 84 , 99 – 106 ). In summary, the adjuvant effect of coadministration of P. acnes with HIVBr18 was evidenced by the potentiation of these responses and the increase in the number of recognized peptides, which generated a broader and more persistent response and reduced the number of administered doses.…”

“…HIV-specific and polyfunctional CD4 + T lymphocytes were shown to be more frequent in long-term non-progressor patients than in patients who rapidly progressed to AIDS ( 99 , 100 ). Therefore, the polyfunctional responses of HIV-specific CD4 + T cells might be potentiated by the presence of P. acnes and might contribute to the control of disease progression ( 101 – 106 ). We also observed higher levels of Th1 cytokines when P. acnes was administered in the first dose than when it was administered in both doses.…”

Fine mapping and conservation analysis of linear B-cell epitopes of peste des petits ruminants virus hemagglutinin protein

“…However, multi-epitope based recombinant vaccines offer numerous advantages compared to the complete protein including cost-effective production, multi-valency, and stability under different conditions. Moreover, the efficacy of epitope vaccines can be further improved by combining CD4 + T helper and promiscuous epitopes, employing epitope enhancement techniques (such as immune-informatics or computational immunology), and adopting toll-like receptor (TLR) ligands as an adjuvant (Nezafat et al, 2014;Rosa et al, 2015). Consequently, in order to enable rational multi-epitope vaccine and diagnostic antigen design, it is imperative to delineate the BCEs on the target antigens.…”

DNA vaccine with discontinuous T‐cell epitope insertions into HSP65 scaffold as a potential means to improve immunogenicity of multi‐epitope Mycobacterium tuberculosis vaccine

“…Epitope-focused vaccine design is an appealing method, by which minimized antigen epitopes are designated to develop into a TB vaccine resulting in retaining one or more key epitopes while eliminating other potentially distracting or unnecessary features (20,34,35). Until now, much evidence has proved that epitope-focused vaccine could effectively protect against cancer and infectious diseases (36)(37)(38)(39)(40).…”