Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines

Abstract

Cats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657x15) the cleavage site and an FIV envelope bacterial fusion protein (␤-Galactosidase-Env) were incorporated into immune-stimulating complexes or adjuvanted with Quil A. Although all immunized cats developed antibodies against the envelope protein, only the cats vaccinated with the rVV-expressed envelope glycoproteins developed antibodies which neutralized FIV infection of Crandell feline kidney cells. These antibodies failed to neutralize infection of thymocytes with a molecularly cloned homologous FIV. After the third immunization the cats were challenged with homologous FIV. Two weeks after challenge the cellassociated viral load proved to be significantly higher in the cats immunized with vGR657 and vGR657x15 than in the other cats. The cats immunized with vGR657 and vGR657x15 also developed antibodies against the Gag proteins more rapidly than the cats immunized with ␤-Galactosidase-Env or the control cats. This suggested that immunization with rVV-expressed glycoprotein of FIV results in enhanced infectivity of FIV. It was shown that the observed enhancement could be transferred to naive cats with plasma collected at the day of challenge.

Vaccine-induced enhancement of viral infections

“…In another study with ISCOM-based vaccines containing several FIV envelope glycoprotein preparations, all the cats that received eukaryotically expressed Env glycoprotein developed Env-specific, virus neutralizing antibodies. These cats became viremic at least 2 weeks earlier than control cats [40]. The increased susceptibility to infection was also seen in naïve cats after transfer of plasma obtained from vaccinated cats.…”

“…Also after vaccination of cats with candidate FIV vaccines enhanced susceptibility rather than protection against infection was observed [38][39][40]. In one study, passive transfer experiments were carried out which demonstrated that antibodies were probably responsible for the observed enhancement of infection [40].…”

“…Also after vaccination of cats with candidate FIV vaccines enhanced susceptibility rather than protection against infection was observed [38][39][40]. In one study, passive transfer experiments were carried out which demonstrated that antibodies were probably responsible for the observed enhancement of infection [40]. Similarly, vaccination of horses against EIAV with a recombinant S protein-induced enhancement of subsequent infection, although the results of in vitro ADE assays did not correlate with the observed enhancement of infection [41][42][43][44][45].…”

Effect of dual-subtype vaccine against feline immunodeficiency virus infection

“…20 showing a neutralizing antibody titer < 1:10 was also protected against challenge with Petaluma virus. Studies have shown inconsistent results on the correlation between protection against FIV infection and the neutralizing antibody titer at the time of challenge Lombardi et al, 1994;Matteucci et al, 1996;Siebelink et al, 1995;Yamamoto et al, 1991b. Hosie and Flynn (1996) found that protection against challenge was correlated with the neutralizing antibody titer measured using a CrFK cell system but not with that measured in a NT assay based on the feline T cell line MBM.…”

“…A variety of vaccine approaches has been evaluated using the FIV model and these include fixed infected-cell, inactivated whole virus, subunit, and recombinant vaccines (Gonin et al, 1995;Hofmann-Lehmann et al, 1995;Hosie, 1994;Hosie and Flynn, 1996;Hosie et al, 1992Hosie et al, , 1995Lombardi et al, 1994;Lutz et al, 1995;Matteucci et al, 1996;Siebelink et al, 1995;Verschoor et al, 1995;Yamamoto et al, 1991bYamamoto et al, , 1993. Of these vaccine approaches, fixed infected cell and inactivated whole virus vaccines have successfully protected cats against homologous F1V challenge (Yamamoto et al, 1991b).…”