Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects

Roff, Shannon; Sanou, Missa; Rathore, Mobeen H.; Levy, Jay A.; Yamamoto, Janet K.

doi:10.1080/21645515.2015.1026500

Cited by 5 publications

(15 citation statements)

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“…Such results suggest that selecting protective T-cell epitopes from the Gag-p24 and Pol-RT may be a better strategy since expression of whole viral proteins do not appear to confer protection. The need for such a selection also infers that viral proteins are composed of epitopes that enhance viral infection as well as epitopes that readily mutate to escape vaccine immunity [ 79 , 85 , 87 , 88 ]. The former case has been demonstrated in a preliminary in vitro study which demonstrated the presence of FIV enhancing epitope nearby a protective T-cell epitope on FIV p24 [ 89 ].…”

Section: A Novel Approach To Confirm the Value Of T-cell Immunity mentioning

confidence: 99%

“…The T-cell functional parameters derived from those observed in the protected IWV-vaccinated cats have been used to identify the conserved T-cell epitopes on FIV p24 and RT that stimulate anti-FIV/HIV T-cell activities in the PBMC of both HIV + human subjects and IWV-vaccinated cats [ 87 , 88 ]. Two FIV p24 peptides and two FIV RT peptides were selected by this method [ 89 ].…”

Section: A Novel Approach To Confirm the Value Of T-cell Immunity mentioning

confidence: 99%

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Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Sahay

Yamamoto

2018

Viruses

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The feline immunodeficiency virus (FIV) vaccine called Fel-O-Vax® FIV is the first commercial FIV vaccine released worldwide for the use in domestic cats against global FIV subtypes (A–E). This vaccine consists of inactivated dual-subtype (A plus D) FIV-infected cells, whereas its prototype vaccine consists of inactivated dual-subtype whole viruses. Both vaccines in experimental trials conferred moderate-to-substantial protection against heterologous strains from homologous and heterologous subtypes. Importantly, a recent case-control field study of Fel-O-Vax-vaccinated cats with outdoor access and ≥3 years of annual vaccine boost, resulted in a vaccine efficacy of 56% in Australia where subtype-A viruses prevail. Remarkably, this protection rate is far better than the protection rate of 31.2% observed in the best HIV-1 vaccine (RV144) trial. Current review describes the findings from the commercial and prototype vaccine trials and compares their immune correlates of protection. The studies described in this review demonstrate the overarching importance of ant-FIV T-cell immunity more than anti-FIV antibody immunity in affording protection. Thus, future efforts in developing the next generation FIV vaccine and the first effective HIV-1 vaccine should consider incorporating highly conserved protective T-cell epitopes together with the conserved protective B-cell epitopes, but without inducing adverse factors that eliminate efficacy.

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Section: A Novel Approach To Confirm the Value Of T-cell Immunity mentioning

confidence: 99%

Section: A Novel Approach To Confirm the Value Of T-cell Immunity mentioning

confidence: 99%

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Sahay

Yamamoto

2018

Viruses

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“…In comparison, T-cell epitopes are short linear peptides processed from a protein antigen, and presented on MHC molecules for their recognition by TCR on T cell to induce its effector function(s). The conserved T-cell epitopes on HIV are identical or similar (homologous) in aa sequences and are conserved among the HIV isolates from the same subtype (type-specific) or from multiple HIV subtypes [ 44 – 46 ], and those evolutionarily preserved are conserved among AIDS lentiviruses of humans, nonhuman primates (NHPs), and cats (HIV, SIV, FIV) [ 47 , 48 ]. Generally, those conserved among HIV/SIV/FIV are often conserved within and among HIV subtypes [ 47 , 48 ].…”

Section: Conserved B-cell and T-cell Epitopes On Hivmentioning

confidence: 99%

“…The conserved T-cell epitopes on HIV are identical or similar (homologous) in aa sequences and are conserved among the HIV isolates from the same subtype (type-specific) or from multiple HIV subtypes [ 44 – 46 ], and those evolutionarily preserved are conserved among AIDS lentiviruses of humans, nonhuman primates (NHPs), and cats (HIV, SIV, FIV) [ 47 , 48 ]. Generally, those conserved among HIV/SIV/FIV are often conserved within and among HIV subtypes [ 47 , 48 ]. The evolutionarily conserved epitopes that maintained their existence among different hosts have lower likelihood to acquire mutation(s) compared to the non-conserved epitopes with variable aa sequences.…”

Section: Conserved B-cell and T-cell Epitopes On Hivmentioning

confidence: 99%

Conserved HIV Epitopes for an Effective HIV Vaccine

Sahay¹,

Nguyen²,

Yamamoto³

2017

J Clin Cell Immunol

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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.

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“…The feline IFNγ and IL-2 ELISpot analyses of PBMC to overlapping peptide pools for FIV p24 and reverse transcriptase (RT) were performed as previously described [28]. CD3 + CD4 + and CD3 + CD8 + T-cell proliferation was determined by FACS using the carboxyfluorescein diacetate succinimide ester (CFSE) method as previously described [29]. Cytokine and cytotoxin mRNA analysis was performed using PBMC and FACS-sorted CD3 + CD4 + and CD3 + CD8 + T cells from donors as previously described [19].…”

Section: Methodsmentioning

confidence: 99%

An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection

Aranyos

Roff

et al. 2016

Vaccine

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The importance of vaccine-induced T-cell immunity in conferring protection with prototype and commercial FIV vaccines is still unclear. Current studies performed adoptive transfer of T cells from prototype FIV-vaccinated cats to partial-to-complete feline leukocyte antigen (FLA)-matched cats a day before either homologous FIVPet or heterologous-subtype pathogenic FIVFC1 challenge. Adoptive-transfer (A–T) conferred a protection rate of 87% (13 of 15, p<0.001) against FIVPet using FLA-matched T cells, whereas all 12 control cats were unprotected. Furthermore, A-T conferred protection rate of 50% (6 of 12, p<0.023) against FIVFC1 using FLA-matched T cells, whereas all 8 control cats were unprotected. Transfer of FLA-matched T and B cells demonstrated that T cells are needed to confer A-T protection. In addition, complete FLA-matching and addition of T-cell numbers >13×106 cells were required for A-T protection against FIVFC1 strain, reported to be a highly pathogenic virus resistant to vaccine-induced neutralizing-antibodies. The addition of FLA-matched B cells alone was not protective. The poor quality of the anti-FIV T-cell immunity induced by the vaccine likely contributed to the lack of protection in an FLA-matched recipient against FIVFC1. The quality of the immune response was determined by the presence of high mRNA levels of cytolysin (perforin) and cytotoxins (granzymes A, B, and H) and T helper-1 cytokines (interferon-γ [IFNγ] and IL2). Increased cytokine, cytolysin and cytotoxin production was detected in the donors which conferred protection in A-T studies. In addition, the CD4+ and CD8+ T-cell proliferation and/or IFNγ responses to FIV p24 and reverse transcriptase increased with each year in cats receiving 1X-3X vaccine boosts over 4 years. These studies demonstrate that anti-FIV T-cell immunity induced by vaccination with a dual-subtype FIV vaccine is essential for prophylactic protection against AIDS lentiviruses such as FIV and potentially HIV-1.

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Conserved epitopes on HIV-1, FIV and SIV p24 proteins are recognized by HIV-1 infected subjects

Cited by 5 publications

References 50 publications

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine

Conserved HIV Epitopes for an Effective HIV Vaccine

An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection

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