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Vaccine against Infections Bovine Rhinotracheitis

#3699


Development of the Experimental DNA Vaccine Preparation for Induction of Mucosal Immunity Against Infectious Bovine Rhinotracheitis

Tech Area / Field

  • BIO-MIB/Microbiology/Biotechnology
  • AGR-VTH/Vaccines and Theraupetics/Agriculture

Status
3 Approved without Funding

Registration date
13.02.2007

Leading Institute
Research Center of Toxicology and Hygienic Regulation of Biopreparations, Russia, Moscow reg., Serpukhov

Supporting institutes

  • Ivanovsky Institute of Virology, Russia, Moscow

Collaborators

  • University of Saskatchewan / Vaccine & Infectious Disease Organization, Canada, SK, Saskatoon\nVIDO, Canada, SK, Saskatoon\nUniversity of Chicago / Department of Molecular Genetics and Cell Biology, USA, IL, Chicago

Project summary

The project objective is development of experimental DNA vaccine preparation for induction of mucosal immunity against the bovine infectious rhinotracheitis (BIRT). BIRT is induced by DNA-containing virus of Herpesviridae superfamily. It is a widely spread acute contagious cattle disease which affects the organisms through mucosa and can be presented in 5 forms, including:
  1. affection of the upper respiratory tract;
  2. vaginitis, endometritis, orchitis, sterility;
  3. encephalitis;
  4. conjunctivitis and;
  5. arthritis.

Solution of the BIRT problem is of great significance for Russian and Canadian economics. BIRT-caused economical loss is expressed in lowering of milk yield from infected animals (by 50-60%), barrenness when vaginal form of disease, slow development of calves and their rejection due to ablepsia.

Anti-BIRT vaccines available at the market are not efficient enough to assure a reliable protection against this disease.

There exist different kinds of live anti-BIRT vaccines. Only in the US 14 variants of live vaccines are being used [14,16]. Most of them are viral strains attenuated by long-time passing in primary and continuous cell cultures. In Belgium and Japan the ts-mutants are in current use. Live vaccines under intranasal and intramuscular delivery provide strong local immunity to protect animals from infection. For vaccination with live vaccines the strains should be used that are incapable of persisting since recombinant may be produced as a result of interaction of attenuated and virulent virus strains. The TK-minus immunogenic mutant capable of persisting in vaccinated calves for no less than 3 months and being transmitted to other calves without reversion to TK+ genotype was proposed as a live vaccine [17].

In the Russian Federation and CIS countries for BIRT prevention live vaccine TK-A developed at the All-Russian Institute for Experimental Veterinary (ARIEV) is currently being used. It is delivered subcutaneously and traumatizing can lead to reducing the quality of the cattle meat products. Immunity in vaccinated animals is maintained for no less than 1 year. Also, “Bivac” vaccine containing 2 vaccine strains (PG-3 and IRT) is being broadly used.

When using live vaccines, persistence and excretion of attenuated BIRT virus strain was found, especially frequently and for a long time - in the sperm of vaccinated bulls [18]. Administration of a live vaccine in the oestral period may be accompanied by affection of ovaries [17]; vaccination in early pregnancy can cause an abortion [19].

Intranasal vaccination is more effective than subcutaneous or intramuscular ones. Intranasally delivered virus easily penetrates into the cells of upper airways and pharynx circle; under genital delivery – into epithelial cells of vagina or preputium. The advantage of intranasal vaccination lies in intensification of IgA synthesis and local production of interferon.

A live polyvalent vaccine based on five types of attenuated viruses (IRT, VD-BS, PG-3, RG and bovine adenovirus type 7) widely spread in Japan and other countries is patent pending. All its components are made in cell cultures. Polyvalence of the preparation enhances the efficacy of vaccination [20].

Also, recombinant vaccines are currently under development. For example, insertion of monomer fragment of the P1 protein gene of the foot-and-mouth disease into gene gIII of the attenuated vaccine strain IRT (NY) has resulted in synthesis of protein, which provides protection of vaccinated calves against BIRT and foot-and-mouth disease.

The other types of the vaccines used are inactivated and sub-unit vaccines based on glycoprotein IV. They offer different efficacy.

There is no direct connection between humoral AB and immunity to BIRT. Even low AB titers can protect animal from infection. Finding of specific AB in blood serum is not a precise indicator of immunity still being a criterion at the immunologic assessment. Most authors believe that virus-neutralizing AB in titers 1:2-1:4 protect animals against infection. Immunization of animals with a live anti-BIRT vaccines helps make lower but not prevent latent BIRT infection.

All above convinces of the necessity to develop and study new-class immunogenic preparations - DNA vaccines. Inhalation is an attractive variant of these vaccines’ delivery, which provides an active inducement of cellular component of immunity and acts in the area of the natural infection entrance specifically stimulating synthesis of immunoglobulin A. This route of DNA-vaccines delivery needs protection of the active agent (DNA). In the proposed project this function is provided by polyethyleneimine, which builds up with DNA a stable complex well associated with alveoli cells due to its cation properties. Development of this complex dissociation means will make it possible to make a precise assessment of the concentration of the active agent for which a cloned gene gD BIRT will be used.

The experience of the proposal authors in molecular biology of herpesviruses, in anti-herpertic DNA vaccine preparations (based on the gene gD of the Herpes simplex virus type 1, HSV1, analogue of gIV of BIRT), and in DNA vaccine inhalation preparations gives a hope to successful realization of the project proposed.


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