A candidate phocid herpesvirus vaccine that provides protection against feline herpesvirus infection
Introduction
To date, two herpesviruses in seals have been identified: (1) phocid herpesvirus type 1 (PhHV-1), an alpha-herpesvirus; and (2) phocid herpesvirus type 2, a tentative gamma-herpesvirus [1], [2]. Like other alpha-herpesvirus infections, PhHV-1 causes disease in its target species, ranging from severe generalised fatal disease in pups to a mild self-limiting upper respiratory tract disease in otherwise healthy adult seals [3]. Outbreaks of PhHV-1 infections are a severe management problem in seal orphanages and rehabilitation centres, and currently no PhHV-1 vaccine is available. Virus vaccines that are used in wild animals or animals that have to be re-introduced in the wild should as a matter of principle not be based on replication competent live attenuated viruses. Therefore, inactivated or subunit vaccines would be preferred. Since vaccines against herpesvirus infections should probably induce adequate T-cell responses, inducing MHC class I restricted cytotoxic T-lymphocyte (CTL) responses, which is usually not achieved by non-replicating vaccines, adjuvants should be used that would allow the induction of adequate T-cell responses with non-replicating antigens. Therefore, in the current study we have chosen to use the presentation of PhHV-1 antigens in ISCOM (for review see [4]). For obvious reasons, possibilities to test candidate vaccines in seals are limited. Given the antigenic and genetic relationship between PhHV-1 and feline herpesvirus (FHV) [1], [2], [5], the FHV–cat system could be considered for the preliminary testing of candidate PhHV-1 vaccines. Here we have tested the efficacy and safety of a candidate PhHV-1 based ISCOM vaccine together with candidate FHV and as a control canine distemper virus (CDV) based ISCOM vaccines prepared in the same way, in the FHV cat system.
Section snippets
Virus preparations
Crandell feline kidney cells (CrFK) and Vero cells were seeded into roller bottles at a concentration of 2.5×106 cells per 100 ml Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 2% penicillin–streptomycin and 5% fetal bovine serum. Once monolayers were formed, CrFK cells were infected at a multiplicity of infection (moi) of approximately 10−4 of either FHV (strain 6887/Han90) [5] or PhHV-1 (strain PB84) [4]. Vero cells were infected with CDV (Bussel strain) at a moi of approximately
Response to vaccination
After each of the three vaccinations with the respective vaccines, the animals were monitored for apparent clinical side effects of vaccination. In none of the animals side effects were observed.
Sera were tested for their ability to neutralise FHV in the presence of 4% (v/v) rabbit serum. The cats in the PhHV-1 ISCOM vaccinated group developed lower levels of cross-neutralising antibodies against FHV than the cats in the FHV ISCOM vaccinated group. Mean antibody responses after vaccinations and
Discussion
In the present paper we have shown that a PhHV-1 based ISCOM vaccine is safe and induces partial cross-protection from FHV disease in cats to a similar extent as an ISCOM based on FHV candidate vaccine. Therefore, we may expect that the tested PhHV-1 vaccine will offer significant protection to PhHV-1 induced disease in seals.
The PhHV-1 ISCOM was effective, as cats of the PhHV-1 ISCOM vaccinated group were protected against development of severe clinical symptoms as measured by the absence of
Acknowledgements
We thank Thijs Kuiken for carefully reviewing the manuscript and Marco van de Bildt for technical assistance.
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