Dual-subtype vaccinated cats developed broad-spectrum humoral and cellular immunity which protected cats against in vivo-derived inocula of homologous and heterologous FIV subtypes. Thus, multi-subtype antigen vaccines may be an effective strategy against AIDS viruses.
Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterization of vaccine immunity in the context of the protection detected with prototype and commercial dual-subtype FIV vaccines and in relation to HIV-1.
Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus
that causes AIDS in domestic cats. FIV is classified into five subtypes
(A–E), and all subtypes and circulating intersubtype recombinants have
been identified throughout the world. A commercial FIV vaccine, consisting of
inactivated subtype-A and –D viruses (Fel-O-Vax FIV, Fort Dodge Animal
Health), was released in the United States in 2002. The United States Department
of Agriculture approved the commercial release of Fel-O-Vax FIV based on two
efficacy trials using 105 laboratory cats and a major safety trial performed on
689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic
efficacy against global FIV subtypes and circulating intersubtype recombinants.
The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell
immunity. Findings from these studies are being used to define the prophylactic
epitopes needed for an HIV-1 vaccine for humans.
Vaccine trials were undertaken to determine whether the Fel-O-Vax FIV, a commercial dual-subtype (subtypes A and D) feline immunodeficiency virus (FIV) vaccine, is effective against a subtype B FIV isolate. Current results demonstrate the Fel-O-Vax FIV to be effective against a subtype B virus, a subtype reported to be the most common in the USA.
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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