Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector
Patent
1997-11-05
2000-05-16
Housel, James C.
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
4242781, 4242041, 4242251, 4242261, 4242271, 42419611, 514 8, 514894, 530322, A61K 3900, A61K 4500, A61K 3929, A61K 3912
Patent
active
060633808
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
(1) Field of the Invention
The present invention relates to an improvement to vaccines containing alum in their compositions and in which the antigen can be partially or completely absorbed on alum. The improvement consists in the combining in the composition constituting these vaccines of 2 to 120 .mu.g per kg body weight, or 0.1 to 6 mg per dose, of muramyl peptide; these vaccines thus improved have, in particular, the advantage of conferring an enhanced immunity, so that the number of injections needed for the immunization is reduced. The only immunoadjuvants currently used in human vaccines are aluminum-based compounds such as aluminum hydroxide or phosphates (alum).
(2) Description of the Related Art
This applies, in particular, to various vaccines in which the active principle consists of an antigen obtained by genetic recombination in vitro, such as Havrix, a hepatitis A vaccine in which the active principle is an antigen obtained from a hepatitis A virus strain cultured in cell culture, and containing aluminum hydroxide in the proportion of 1.5 mg per dose (0.5 mg of aluminum) and marketed by the company Smith Kline & French (6, Esplanade Charles De Gaulle, 92731 Nanterre Cedex), under the trade name Havrix. Two administrations performed at an interval of one month enable seroconversion to be induced in 98% of individuals.
Three recombinant vaccines against the hepatitis B virus are currently on the market; they are: LYON FRANCE), which vaccine contains not more than 3.5 mg of aluminum hydroxide per dose, hydroxide per dose, aluminum hydroxide per dose.
The hepatitis B vaccines mentioned above are effective only after at least three injections at 0, 30 and 60 or 180 days, followed by an obligatory booster after one year; in addition, a number of subjects are poor responders or nonresponders. In the total population, they represent approximately 5%, and the capacity to obtain seroconversion depends greatly on the subject's age; it is already significantly smaller from 30-35 years onwards. Furthermore, there are groups which are especially poor responders, namely hemodialysis patients (30 to 45% of that population) and renal transplant recipients, 75 to 95% of whom do not respond to vaccines. Various investigations have studied this resistance to immunization with hepatitis B vaccines: the investigations of Stevens et al. (1), Zachoval et al. (2) and Grob PJ et al. (3) should be mentioned. This problem of lack of response to a hepatitis B vaccine becomes extremely serious in countries in which this viral infection has substantial endemic character and where approximately 5% of the population represents a considerable number of individuals; it is, in addition, especially critical in at-risk populations such as hemodialysis patients, who are rightly driven to undergo a large number of blood transfusions with the subsequent risks of viral contamination. Lastly, the fact of having to perform not less than three injections followed by a booster in order to immunize responder patients, the fourth injection coming one year after the first, represents an especially difficult and risky follow-up situation.
The problem of developing a vaccine which can, on the one hand, confer on existing nonresponders an immunization against a hepatitis virus infection, and, on the other hand, enable the number of vaccinating doses to be decreased in normal responders, permitting a follow up and a much more rigorous prophylaxis in regions where the infection is endemic or in at-risk populations, proves to be a medical necessity.
Another problem arising for the prophylaxis of hepatitis in regions where the infection is endemic is to produce a mixed vaccine against the different kinds of hepatitis, and in particular hepatitis A and B. At the present time, double vaccination against hepatitis A and B necessitates six injections, four of them for hepatitis B and two for hepatitis A; thus, the prophylaxis of hepatitis would be advantageously improved by: immunization against infection by both of these
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Audibert Francoise
Chedid Louis
Devi S.
Housel James C.
Vacsyn S.A.
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