Cross-clade immunity in cats vaccinated with a canarypox-vectored avian influenza vaccine
Introduction
The unprecedented spread of highly pathogenic avian influenza (HPAI) A virus of the H5N1 subtype throughout southeast Asia, Europe, the Middle East and Africa since the mid-nineties, leading to huge morbidity and mortality among domestic and wild birds, has also led to infection in many mammalian species including humans and several carnivore species. More than 450 severe human cases have been reported with a case fatality rate of approximately 60% [1] and a substantial number of outbreaks of H5N1 with high mortality have been documented in felids, including tigers and domestic cats [2]. Like other influenza A virus subtypes, HPAI H5N1 viruses continuously evolve through antigenic drift, at a rate that is alarmingly higher than for the predominant seasonal human variants (H3N2 and H1N1). Today, two different clades (clades 1 and 2), and several lineages within these clades of H5N1 have been identified which predominate in distinct geographic locations [3]. Clade 1 viruses have been isolated in Vietnam, Thailand, Cambodia and Malaysia, while clade 2 viruses of different subclades have caused outbreaks in Indonesia and China, but also in Europe, the Middle East and West Africa. Both clades have been shown to infect felids in the field, and in an experimental setting, challenge of domestic cats with a HPAI H5N1 virus (clade 1) isolated from a human case in Vietnam led to a severe generalized infection. In these experiments, cat-to cat transmission was also documented [4]. These observations suggest that domestic cats may be involved in the transmission of the virus to other animals and to humans. Cats might also play a role in the adaptation of the virus to mammalian species, contributing to the pandemic risk [5]. Therefore, the development of a HPAI vaccine for domestic cats should be considered a veterinary and also a public health priority.
In this study, we tested a recombinant canarypox virus (ALVAC®) expressing the hemagglutinin (HA) of influenza virus A/chicken/Indonesia/03 (H5N1) in a HPAI H5N1 virus vaccination-challenge model in cats. ALVAC recombinant vaccines have been shown to induce protective immune responses against several infectious agents [6]. The canarypox virus vector has two important natural properties: it is a non-replicative vector for mammalian species [7], and anti-vector immunity has not been shown to interfere with the efficacy of subsequent booster vaccination with the same vector [8], at least, in veterinary vaccine development efforts.
Following two doses of the ALVAC H5N1 vaccine candidate, all vaccinated cats were effectively protected against intratracheal challenge with wild-type influenza virus A/Vietnam/1194/2004 (H5N1, clade 1) and A/Indonesia/05/2005 (H5N1, clade 2.1).
Section snippets
Cats
Twenty-four specific pathogen-free European short-hair cats were purchased from Charles River Laboratories, France. They were approximately 4 or 5 months old at the time of the first vaccine injection, and all were seronegative for influenza virus type A and B.
Two weeks before vaccination, a body temperature probe (Star-Oddi, Reykjavik, Iceland) was implanted into the peritoneal cavity of each animal. Before challenge, the animals were housed in groups of four or five. After challenge, the
Vaccine-induced HI antibody response
Fourteen days after the first injection of vCP2241, 6 of the 12 vaccinated cats seroconverted against A/chicken/Indonesia/7/03, and none against A/Vietnam/1194/04. Fourteen days after the second injection of vCP2241, all cats had HI titers against A/chicken/Indonesia/7/03, ranging from 1.2 to 2.4 log10 HI units/mL, and 4 out of 12 cats had low antibody titers against A/Vietnam/1194/04 (Table 1).
Clinical signs (Table 2)
Two controls were found dead on day 4 and 6 post-infection (p.i.). Two other controls were moribund and
Discussion
In this study, the efficacy of a canarypox-vectored vaccine expressing the HA of a highly pathogenic H5N1 strain was tested against homologous and heterologous HPAI virus (HPAIV) challenges in cats. Heterologous challenge was done with A/Vietnam/1194/2004, a HPAIV from a different clade, which has been shown to be highly virulent in cats [12].
Infection with the A/Vietnam/1194/2004 strain or the A/Indonesia/05/2005 strain resulted in severe lethargy, fever, anorexia, weight loss, severe
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