Live attenuated vaccines against feline infectious peritonitis virus and other feline pathogens (UDG.6029)

Project nummer: udg6029

Omschrijving van het onderzoek

Feline infectious peritonitis (FIP) is a fatal disease of cats caused by a coronavirus, the feline infectious peritonitis virus (FIPV) of which two serotypes (I and II) occur. Currently, the virus is the leading infectious cause of mortality in young cats in pedigree catteries and shelters. Becuase an effective vaccine is not available, our aim is to develope one. In a current CW/STW project (#349-4600, ending September 1, 2002) our lab established a system for reverse genetics of FIPV (serotype II) based on targeted RNA recombination. Using this new systemwe rationally designed attenuated viruses by deletion of genes implicated in viral virulence. We showed, for the first time, that oronasal vaccination with these deletion viruses can protect cats against FIP when challenged with homologous (i.e. serotype II) virulent FIPV. These viruses, which are presently being tested against serotype I FIPV, are obviously excellent candidate vaccines. Live attenuated virus vaccines are generally superior over other types of vaccines as they can elicit the broadest spectrum of immune responses, including mucosal responses when applied oronasally.
The primary objective of this proposal is to develop the above vaccine candidates into a save vaccine that will protect against both feline coronavirus (FCoV) serotypes. The safety aspect will be adressed by changing the gene order in the attenuated deletion viruses: we will relocate the N gene to a position upstream of the S gene, a major genomic rearrangement tolerated without loss of fitness by the mouse coronavirus MHV-A59. This will minimize the chances of generating viable viruses by recombination of our live coronaviral vaccines with virulent coronaviruses circulating in the field. In addition, the rearrangement is expected to further attenuate the vaccine viruses. If these viruses would appear not to protect (sufficiently) against serotype I viruses, we will engineer derivates that express a type I spike gene construct in order to obtain the vaccine(s) that will provide the desired broad protection.
Our second objective is to develop these genomically rearranged deletion viruses into vaccine vectors by inserting sequences known to encode important antigens from other feline pathogens. Thus, an env gene fragment on the feline leukemia virus (FeLV), a major feline pathogen, will be incorporated into the above FIPV vaccine virus. The resulting chimeric virus will be characterized in vitro and subsequently tested for its efficacy as a combination vaccine not only against FIPV but also against a challenge with FeLV.
The deletion of viral genes involved in virulence combined with the rearrangement of the order of the essential genes and the insertion of genes from other pathogens is a unique and original approach to vaccine development. We have demonstrated the feasibility of this approach in recent model studies using a murine coronavirus.

Gebruikers

Er zijn twee bedrijven bij dit project betrokken.

Projectleider

Prof.dr. P.J.M. Rottier

Universiteit Utrecht
Diergeneeskunde
Infectieziekten & Immunologie

Postbus 80165
3508 TD Utrecht

Status van het project

Gestart	: 01-03-2003
Einddatum	: 16-10-2007

Trefwoorden

Biotechnologie, Diergeneeskunde, Immunologie, Moleculaire biologie, Vaccin, Vaccin ontwikkeling, Virologie

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