Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Pistello, Mauro; Bonci, Francesca; Zabogli, Elisa; Conti, Francesca; Freer, Giulia; Maggi, Fabrizio; Stevenson, Mario; Bendinelli, Mauro

doi:10.1128/jvi.02638-09

Cited by 10 publications

(9 citation statements)

References 70 publications

(92 reference statements)

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“…A recent study showed that immunization with FIV Pet Env-expressing autologous T cells conferred protection against a homologous challenge and correlated with immunization-induced NAbs [41]. In line with this, both active and passive immunizations in our studies conferred protection against homologous tier-1 FIV Pet .…”

Section: Discussionsupporting

confidence: 87%

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

Coleman

Martin

et al. 2014

Vaccine

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A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax® FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F′/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37–41 weeks) studies. In long-duration (76–80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs.

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Section: Discussionsupporting

confidence: 87%

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

Coleman

Martin

et al. 2014

Vaccine

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“…Plasmids p239SpSp5= and p239SpE3=, encoding the SIVmac239 molecular clone 5= and 3= ends, respectively (30,49), were obtained through the AIDS Research and Reference Reagent Program (ARRP), Division of AIDS, NIAID, NIH. The plasmid encoding the envelope of the in vivo-readapted FIV strain Petaluma (FIV-Petaluma) (pEE14-Env) was described elsewhere previously (47).…”

Section: Methodsmentioning

confidence: 99%

Feline Tetherin Is Characterized by a Short N-Terminal Region and Is Counteracted by the Feline Immunodeficiency Virus Envelope Glycoprotein

Celestino

Calistri

Vecchio

et al. 2012

J Virol

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dTetherin (BST2) is the host cell factor that blocks the particle release of some enveloped viruses. Two putative feline tetherin proteins differing at the level of the N-terminal coding region have recently been described and tested for their antiviral activity. By cloning and comparing the two reported feline tetherins (called here cBST2 504 and cBST2*) and generating specific derivative mutants, this study provides evidence that feline tetherin has a shorter intracytoplasmic domain than those of other known homologues. The minimal tetherin promoter was identified and assayed for its ability to drive tetherin expression in an alpha interferon-inducible manner. We also demonstrated that cBST2 504 is able to dimerize, is localized at the cellular membrane, and impairs human immunodeficiency virus type 1 (HIV-1) particle release, regardless of the presence of the Vpu antagonist accessory protein. While cBST2 504 failed to restrict wild-type feline immunodeficiency virus (FIV) egress, FIV mutants, bearing a frameshift at the level of the envelope-encoding region, were potently blocked. The transient expression of the FIV envelope glycoprotein was able to rescue mutant particle release from feline tetherin-positive cells but did not antagonize human BST2 activity. Moreover, cBST2 504 was capable of specifically immunoprecipitating the FIV envelope glycoprotein. Finally, cBST2 504 also exerted its function on HIV-2 ROD10 and on the simian immunodeficiency virus SIVmac239. Taken together, these results show that feline tetherin does indeed have a short N-terminal region and that the FIV envelope glycoprotein is the predominant factor counteracting tetherin restriction.

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“…Although the result from Study 1 is not statistically significant, T cells appeared to be involved in conferring A-T protection, but the number of B-cell recipients was too small to determine whether B cells alone can confer A-T protection. In regards to the potential of B cells to afford protection to recipients of A-T, studies by others have shown that the commercial dual-subtype FIV vaccine [31] as well as priming T cells with FIV Pet Env pDNA [32] induced high NAbs to FIV Pet . However, in current studies, all recipients of A-T from vaccinated cats, except for the unprotected recipients, had no NAbs to FIV Pet or FIV FC1 (data not shown) and no FIV Abs (Tables 2 and 3, immunoblot).…”

Section: Discussionmentioning

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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Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Cited by 10 publications

References 70 publications

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies

Feline Tetherin Is Characterized by a Short N-Terminal Region and Is Counteracted by the Feline Immunodeficiency Virus Envelope Glycoprotein

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

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