Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1997-09-15
1999-11-16
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
424 934, 4242551, 4241844, 435 691, 435 693, 435 711, 4351723, A61K 3902, A61K 39102, A01N 6300, C12P 2106
Patent
active
059852852
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel vaccines for provision of protection against infection with the organism Yersinia pestis and to methods for administering these. Particularly provided are parenterally and orally active vaccines capable of offering protection against bubonic and pneumonic plague. particularly by induction of mucosal immunity in both humans and other animals.
Yersinia pestis is the highly virulent causative organism of plague in a wide range of animals, including man. Infection with such organisms results in a high rate of mortality. Studies have shown that the high virulence is due to a complex array of factors encoded by both the chromosome and three plasmids, including the Lcr genes, a fibrinolysin and a capsule.
Man is an occasional host in the natural cycle of the disease, and bubonic plague, characterised by the swelling of local lymph nodes, may occur following the bite of an infected flea. One of the complications of bubonic plague is secondary pneumonia, and in these cases the disease is readily transmitted between humans by airborne droplets. Plague is endemic in regions of North and South America, Africa, China and Asia (see Butler (1983) Plague and Other Yersinia Infections; Plenum Press, New York). Current outbreaks are believed to be part of the fourth world pandemic of the disease, with a clear need to protect individuals living or travelling in endemic areas, and laboratory workers handling the bacterium.
The current whole cell vaccines available for prevention of plague are highly heterogeneous. resulting in side effects which make them unsuitable for widespread use (eg Meyer et al (1974) J. Infect Dis 129 supp 13-18 and 85-120: Marshall et al (1974) ibid supp 19-25).
One current vaccine for plague is the Cutter vaccine which comprises formaldehyde killed plague bacilli and is administered to the body by intramuscular injection. However, parenteral immunisation, although effective in inducing systemic immunity, does not effectively induce mucosal immunity (McGhee et al, (1992) Vaccine 10, 75-88) and cases of pneumonic plague have been reported in vaccinated individuals (Meyer (1970) Bull WHO 42 p663-668). So far no vaccine capable of producing a protective immune response at mucosal surfaces has been reported.
The live attenuated EV76 vaccine was tested extensively and used in the former Soviet Union from 1939, although its efficacy in evoking an immune response in man is questionable (Meyer et al (1974) J. Infect. Dis. 129 Supp: 13-18). It has been shown that the virulence of EV76 differs in several animal species. and non-human primates are particularly susceptible to a chronic infection with this strain. In the Western World the vaccine is considered to be unsuitable for mass vaccinations due to the extreme severity of the side effects and the possibility of the strain reverting to full virulence.
Two known Y. pestis antigens are the Y. pestis LcrV (V antigen), and the Fl antigen: both of which have now been found to be capable of evoking protective immune responses in animals. The present inventors have previously provided live orally active vaccine microorganisms capable of expressing V antigen and F1 antigen respectively which each provide good protection against challenge with Y. pestis at up to 10.sup.3 cfu. These vaccines are the subject of copending patent applications PCTIGB94/02818 and GB 9404577.0.
The present inventors have now surprisingly found that whereas only the unacceptably hazardous EV live vaccine had been shown to be capable of giving good protection against challenge with 10.sup.9 cfu or more with Y. pestis GB strain, and V and F1 antigens alone only provide full protection against challenge with about 10.sup.5 cfu. by administering a combined vaccine comprising V and F1 antigens they can at least match the protection afforded by EV76 without any of the hazards that have kept the EV vaccine from general use.
Still more advantageously, they have found that the vehicle for administration may be a simple mixture of the two protein components, rath
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Bennett Alice M
Leary Sophie E C
Oyston Petra C F
Titball Richard W
Williamson Ethel D
Devi S.
Housel James C.
The Secretary of State for Defence in Her Britanic Majesty's Gov
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