Conserved HIV Epitopes for an Effective HIV Vaccine

Abstract

Despite major advances in antiretroviral therapy against HIV-1, an effective HIV vaccine is urgently required to reduce the number of new cases of HIV infections in the world. Vaccines are the ultimate tool in the medical arsenal to control and prevent the spread of infectious diseases such as HIV/AIDS. Several failed phase-IIb to –III clinical vaccine trials against HIV-1 in the past generated a plethora of information that could be used for better designing of an effective HIV vaccine in the future. Most of the tested vaccine candidates produced strong humoral responses against the HIV proteins; however, failed to protect due to: 1) the low levels and the narrow breadth of the HIV-1 neutralizing antibodies and the HIV-specific antibody-dependent Fc-mediated effector activities, 2) the low levels and the poor quality of the anti-HIV T-cell responses, and 3) the excessive responses to immunodominant non-protective HIV epitopes, which in some cases blocked the protective immunity and/or enhanced HIV infection. The B-cell epitopes on HIV for producing broadly neutralizing antibodies (bNAbs) against HIV have been extensively characterized, and the next step is to develop bNAb epitope immunogen for HIV vaccine. The bNAb epitopes are often conformational epitopes and therefore more difficult to construct as vaccine immunogen and likely to include immunodominant non-protective HIV epitopes. In comparison, T-cell epitopes are short linear peptides which are easier to construct into vaccine immunogen free of immunodominant non-protective epitopes. However, its difficulty lies in identifying the T-cell epitopes conserved among HIV subtypes and induce long-lasting, potent polyfunctional T-cell and cytotoxic T lymphocyte (CTL) activities against HIV. In addition, these protective T-cell epitopes must be recognized by the HLA prevalent in the country(s) targeted for the vaccine trial. In conclusion, extending from the findings from previous vaccine trials, future vaccines should combine both T- and B-cell epitopes as vaccine immunogen to induce multitude of broad and potent immune effector activities required for sterilizing protection against global HIV subtypes.

Artificial Epitope-Based Immunogens in HIV-Vaccine Design

“…This approach seems to be rather promising when developing new generation HIV-vaccines. In theory, it makes it possible to overcome HIV-1 antigenic variability, focus immune responses on protective epitopes and allows to exclude undesirable determinants from a vaccine compound capable of inducing autoantibodies or antibodies increasing virus infectivity [3,4,13]. This paper discusses our experience in designing artificial polyepitope antigens -HIV-1 candidate vaccines.…”

“…Firstly, although trimers are rather stable in solution, they produce conformational conditions that fail to provide binding and induction of bNAbs. Secondly, trimers expose undesired immunodominant non-protective HIV epitopes that could prevent adaptive immune response from recognizing neutralizing epitopes, block protective immunity and/or induce increased HIVinfection [4,36].…”

“…However, for HIV-1 and for many other chronic viral, bacterial, fungal and parasitic infections, and cancer natural immunity is insufficient for protection [1,2]. Novel and effective approaches in polyepitope HIV-vaccine development are needed today [3,4].…”

Immunogenicity assessment of fungal l-asparaginases: an in silico approach

“…3 Relative frequency of allergenic T-cell epitopes for the HLA-DRB1*07: 01 allele for the ten microorganisms studied. A high epitope density was observed for fungal asparaginases B-cell epitope identification has been a widely used approach in peptide-based vaccine design and disease diagnosis [104][105][106]. Additionally, we identify the linear B-cell epitopes present in the nine fungal and E.coli ASNase.…”

Epitope-based vaccine as a universal vaccination strategy against Toxoplasma gondii infection: A mini-review

“…Numerous studies identified potential epitope-based antigens that could effectively induce high and protective immunity against diverse pathogens. The approach has been used to develop and evaluate vaccines to various infectious agents, such as Influenza Virus [52], Human Immunodeficiency Virus [53], Epstein-Barr Virus [19], and hepatitis B virus [54].…”