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

Abstract

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.

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

“…The harvest culture samples were analyzed to determine HIV-1 titer by RT assay. 17 Results are shown as end-point dilution titer of samples from 2 to 3 studies using PBMC from different HIV ¡ donors.…”

“…17 Both the prototype and commercial vaccines induced moderate levels of homologous and fewer heterologous subtype-specific FIV NAbs, but induced strong T-cell responses against both homologous and heterologous subtype FIV strains. 17,18 Using the FIV model, previous studies demonstrated that an experimental HIV-1 p24 vaccine conferred cross-protection against low-dose FIV challenge which indicated that potential vaccine epitopes for FIV protection likely reside on viral p24. 19 Host responses to HIV-1 and SIV p24 antigens are associated with control of virus load.…”

The epidemiology features of retroviral infections in domestic cats from the Zagreb urban area

“…On the other hand, the prevalence of FIV infection has not altered since the virus was discovered in 1986 (PEDERSEN et al, 1987). The vaccine against FIV was not introduced until 2002 and its efficiency is still under debate, while the heterogeneity of the gene sequences poses a great problem for developing a broadly affective and protective vaccine again different subtypes of FIV (ELYAR et al, 1997;LEVY et al, 2008;COLEMAN et al, 2014). Retroviral seroprevalence is highly variable in different geographical areas as well as in different domestic cat categories.…”

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

“…Furthermore, this FIV isolate was resistant to vaccine-induced FIV NAbs based on in vitro testing and an in vivo passive-transfer study using vaccine-induced purified antibodies. Hence, the most likely mechanism of such protection was reported to be the vaccine-induced cellular immunity such as T-cell immunity [18–21]. This observation was also supported by an earlier study which determined high levels of T-cell immunity generated by cats vaccinated with the prototype FIV vaccine [19].…”

“…In the FIV/cat model of HIV/AIDS, the prototype (inactivated whole virus [IWV]) and the commercial (inactivated whole cell lysate) dual-subtype FIV vaccines, composed of subtypes A and D, conferred protection against the heterologous subtype-B FIV FC1 isolate [21]. Furthermore, this FIV isolate was resistant to vaccine-induced FIV NAbs based on in vitro testing and an in vivo passive-transfer study using vaccine-induced purified antibodies.…”