Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Recombinant virus encoding one or more heterologous proteins...
Reexamination Certificate
2001-02-16
2003-05-06
Salimi, Ali R. (Department: 1648)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Recombinant virus encoding one or more heterologous proteins...
C424S204100, C424S202100, C424S209100, C435S320100, C536S023720
Reexamination Certificate
active
06558674
ABSTRACT:
The present invention relates to a vaccine formulation for vaccinating equidae, in particular horses. It also relates to a corresponding vaccination method.
A relatively wide variety of horse pathologies exist. Apart from the well-known respiratory pathologies, such as rhinopneumonitis and influenza, horses are susceptible, in particular on the American continent, to various encephalomyelites. Finally, horses exhibit a variety of other pathologies among which tetanus, Lyme disease and equine arteritis may be mentioned, in particular, without forgetting the risks of exposure to the rabies virus.
The circumstances under which horses are exposed to various pathogenic microorganisms have been increased by the movement of large numbers of horses over substantial distances by land or by air, such that the risk of infection tends to increase.
However, in view of the high cost of these animals, in particular in the case of breeding animals, saddle horses and racehorses, it is economically important to control, as far as possible, the risks of infection, which translate into the animal being unavailable for long periods, if not actually being lost. A certain number of horse vaccines, whose efficacy varies, already exist.
Thus, inactivated or subunit vaccines, all of which, however exhibit some limitations expressed as incomplete or short-term protection and, possibly, safety problems linked to the adjuvants employed, have been developed for the equine rhinopneumonitis which is caused by the different strains of equine herpesvirus (EHV).
Attempts are also being made to use vaccination to prevent equine influenza, which is another important pathology. The vaccines employed are inactivated or subunit vaccines which, while they are effective to a certain degree, are nevertheless not without problems. Thus, protection is frequently not complete and is generally of a relatively brief duration, thereby requiring revaccinations, as in the case of rhinopneumonitis. Safety problems may also be encountered.
Vaccines based on antitetanus toxoid have also been developed and are undeniably effective.
Vaccines against encephalomyelites, some eastern encephalomyelites, western encephalomyelitis and Venezuelan encephalomyelitis, whose efficacy is still poorly known, also exist.
For reasons of economy, on the one hand, and the rational management of equine vaccinations on the other, multivalent vaccine formulations have already been proposed for preventing several of these infectious diseases.
The combinations which have so far been developed have been achieved using inactivated vaccines or live vaccines and, where appropriate, mixtures of these vaccines. Their implementation poses problems of compatibility between valencies and of stability. Thus, it is necessary to ensure compatibility between the different valencies, both with regard to the different antigens employed and with regard to the formulations themselves, in particular when inactivated vaccines and live vaccines are combined at the same time. There is also the problem of preserving such combined vaccines and also that of their safety, in particular in the presence of adjuvant. In general, these vaccines are relatively expensive.
Furthermore, these formulations have not enabled three of the main valencies, namely the equine influenza, rhinopneumonitis, in particular EHV-1 and EHV-4, and tetanus valencies, to be combined. For example, combinations of the influenza and encephalomyelitis valencies, or of the rhinopneumonitis and encephalomyelitis valencies, are known.
The Patent Applications WO-A-90 11 092, WO-A-93 19 183, WO-A-94 21 797 and WO-A-95 20 660 have proposed using the recently developed technique of polynucleotide vaccines. It is known that these vaccines use a plasmid which is capable of expressing, in the host cells, the antigen which is inserted into the plasmid. All the routes of administration have been proposed (intraperitoneal, intravenous, intramuscular, transcutaneous, intradermal, mucosal, etc.). Different means of vaccination may also be used, such as DNA deposited on the surface of gold particles and projected so as to penetrate into the skin of the animal (Tang et al., Nature 356, 152-154, 1992) and injections by means of a liquid jet, which makes it possible to transfect, at one and the same time, skin, muscle, fatty tissues and mammary tissues (Furth et al., Analytical Biochemistry, 205, 365-368, 1992) (See also U.S. Pat. Nos. 5,846,946, 5,620,896, 5,643,578, 5,580,589, 5,589,466, 5,693,622, and 5,703,055; Science, 259:1745-49, 1993; Robinson et al., seminars in IMMUNOLOGY, 9:271-83, 1997; Luke et al., J. Infect. Dis. 175(1):91-97, 1997; Norman et al., Vaccine, 15(8):801-803, 1997; Bourne et al., The Journal of Infectious Disease, 173:800-7, 1996; and, note that generally a plasmid for a vaccine or immunological composition can comprise DNA encoding an antigen operatively linked to regulatory sequences which control expression or expression and secretion of the antigen from a host cell, e.g., a mammalian cell; for instance, from upstream to downstream, DNA for a promoter, DNA for a eukaryotic leader peptide for secretion, DNA for the antigen, and DNA encoding a terminator.
The polynucleotide vaccines can use both naked DNAs and formulated DNAs, for example within liposomes or cationic lipids.
Polynucleotide vectors which integrate the HA or NT genes have been tried out in mice, ferrets and chickens in the case of the influenza virus. No data are available for the horse.
With regard to tetanus, it has recently been reported that immunization of mice with a plasmid which expresses the non-toxic C-terminal region of the tetanus toxin, together with the C fragment, induced the appearance of seroprotective antibodies in the mouse.
However, it is not possible to transpose directly the teaching of the results obtained in these animals of short lifespan to other mammals, in particular mammals of large size.
There is still a requirement, therefore, to improve the protection of equidae, in particular horses, against infectious pathologies.
The invention proposes to provide a multivalent vaccine formulation which makes it possible to vaccinate equidae, in particular horses, against a number of pathogenic agents.
Another object of the invention is to provide such a vaccine formulation which combines different valencies while at the same time exhibiting the requisite criteria of compatibility and stability of the valencies between themselves.
Another object of the invention is to provide such a vaccine formulation which makes it possible to combine different valencies in one and the same excipient.
Another object of the invention is to provide such a vaccine formulation which is easy to implement and inexpensive.
Yet another object of the invention is to provide such a formulation and a method of vaccinating horses which makes it possible to obtain a protection, including a multivalent protection, which is associated with a high level of efficacy and is of long duration while exhibiting a high degree of safety.
The present invention therefore relates to a vaccine formulation against pathologies of equidae, in particular horses, which comprises at least 3 polynucleotide vaccine valencies, each of which comprises an plasmid integrating so as to express it, in vivo in the cells, a gene of an equine pathogen valency, with these valencies being selected from the group consisting of equine rhinopneumonitis virus, EHV, equine influenza virus, EIV, and tetanus (Cl. tetani), with these plasmids comprising, for each valency, one or more of the genes selected from the group consisting of gB and gD in the case of the equine rhinopneumonitis virus, HA, NP and N in the case of the equine influenza virus, and a gene which encodes all or part of the C subunit of the tetanus toxin.
In the present invention, valency is understood as meaning at least one antigen which ensures protection against the virus of the pathogen under consideration, with the valency being able to contain, as a subvalency, one or more natural or modified genes of one or more
Audonnet Jean-Christophe
Bouchardon Annabelle
Riviere Michel
Frommer William S.
Frommer & Lawrence & Haug LLP
Kowalski Thomas J.
Merial
Salimi Ali R.
LandOfFree
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