Chemistry: molecular biology and microbiology – Kit
Patent
1998-04-29
2000-10-24
Wilson, James O.
Chemistry: molecular biology and microbiology
Kit
424 7808, 424 941, 4241841, 4242061, 435236, 435238, 514 55, 514888, 530387, 530404, 530406, 530413, G01N 3353
Patent
active
061366064
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a vaccine composition in the form of a kit comprising a first container containing an antigenic preparation comprising influenza virus antigens and a second container containing a mucosal adjuvant. The invention also relates to a method of immunising a patient against influenza by administering the said composition to the patient, and a method of enhancing the immunogenicity of an influenza viral antigen, particularly when administered intranasally, by co-administering therewith the said adjuvant.
Current influenza vaccines consist of either inactivated whole virus, disrupted virus (split vaccines) or purified preparations of the membrane glycoproteins haemagglutinin (HA) and neuraminidase (NA) sub-unit vaccines. Haemagglutinin and neuraminidase are the antigens to which protective antibody responses are directed, haemagglutinin being the major protective antigen. Estimates of the efficacy of these parenterally administered vaccines vary greatly. Such vaccines are believed to act primarily by eliciting circulating anti-haemagglutinin lgG antibodies that transudate into the lower respiratory tract.
M. L. Clements et al, J. Clinical Microbiology 24, 157-160, 1986, have previously reported that both secretory IgA and serum lgG participate in immunity to influenza virus. Moreover, in mice, a number of published studies have demonstrated the importance of respiratory IgA to protection against influenza infection. It has also been found that an advantage of stimulating a local IgA response to influenza is that it is often of a broader specificity than the serum response and thus can provide cross-protection against viruses possessing haemagglutinin molecules different from those present in the vaccine. Accordingly, influenza vaccines that elicit both local secretory and serum anti-haemagglutinin responses should provide superior immunity to current vaccines. However, parenteral vaccination (intramuscular, sub-cutaneous etc) is not effective at eliciting local antibody production, if there has been no previous mucosal exposure (e.g. infection). In order to stimulate the mucosal immune system, the vaccine must be applied topically to a mucosal surface.
Mucosal administration of influenza vaccine would have a number of advantages over traditional parenteral immunisation regimes. Paramount amongst these are more effective stimulation of the local mucosal immune system of the respiratory tract and the likelihood that vaccine uptake rates would be increased because the fear and discomfort associated with injections would be avoided. Accordingly, a number of attempts have been made to develop mucosal influenza vaccines. A drawback however is that inactivated vaccines are often poorly immunogenic when given mucosally. For example, Kuno-sakai et al (vaccine 12:1303-1310, (1994) have shown that administration of inactivated vaccine to humans gave strong mucosal and serum antibody responses and was effective in preventing infection by live vaccine virus. However, in order to achieve such results, Kuno-sakai et al administered three times the commercially available dose, an approach which is not considered to be commercially viable. In order to overcome this problem, different approaches to improving the immunogenicity of flu vaccines given orally or intranasally have included the use of the B sub-unit of cholera toxin (CTB) as an adjuvant (see S. Tamura et al, vaccine, 6, 409, (1988), encapsulation of the vaccine in a variety of microspheres (see Z. Moldoveanu et al, J.lnf.Dis. 167, 85-90 (1993), and the use of live attenuated strains (see H. F. Maassab et al, vaccines, Plotkin S. A and Mortimer F. A Jr (eds) W. B. Saunders Philadelphia p435 (1993). To date however, no practical means of enhancing the immunogenicity of mucosally administered flu vaccines has been developed.
It has now been found by the Applicants that by administering influenza antigens such as the haemagglutinin and neuraminidase antigens in combination with a particular chitosan derivative, it is possible to achieve good IgG and
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Medeva Holdings BV
Wilson James O.
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