Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific... – Synthetic polymer or copolymer
Reexamination Certificate
1999-06-11
2003-08-26
Krass, Frederick (Department: 1614)
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
Synthetic polymer or copolymer
C424S278100, C424S184100, C424S078080, C424S078170, C424S078180, C424S078310, C424S434000, C424S435000, C514S885000
Reexamination Certificate
active
06610310
ABSTRACT:
This invention relates to novel vaccine compositions, processes for the preparation thereof and methods for the use thereof for the mucosal (nonparenteral) immunization of warm blooded animals.
There are two main types of immunity which may provide a host organism protection against disease and/or infection: systemic (or general) immunity which is provided through parenteral vaccination; and mucosal (or local) immunity which is provided through nonparenteral vaccination.
Traditionally, vaccine development has focused on the induction of systemic immunity, including humoral (specific antibodies of IgM or IgG class) and cellular immune responses (activated T lymphocytes, activated macrophages, or others) through the use of parenteral vaccines. Such parenteral vaccines are administered through, inter alia, intramuscular or subcutaneous routes.
While providing systemic immunity through the use of parenteral vaccines and parenteral vaccination has been proven to be effective in establishing protective immunity against many different pathogens, this is not always the case. Numerous examples exist where such immunity has been proven to be wholly or partially ineffective. Furthermore, parenteral vaccines and parenteral vaccination to provide systemic immunity has other disadvantages, such as the need to breach the integrity of the skin of the organism being immunized therewith, difficulty of administration (needing, for example, trained personnel to administer such vaccines), the high grade of purity needed for such vaccines, a lack of establishment of immunity at the site of natural infection, nonprevention of infection and less than complete protection of the organism against both clinical and nonclinical symptoms of the infection as well as against the infection itself. Further, parenteral vaccines can present problems where the effective immunization of immnunocompromised hosts (i.e., young animals with maternal antibodies) is desired.
A multitude of pathogens naturally infect their hosts via the mucosal (e.g. the respiratory, gastrointestinal or genital) tissues. Mucosal (or local) immunity results from the local formation and secretion of antibodies of the IgA class. These antibodies form dimers which can be secreted into the lumen of respiratory, gastro-intestinal or genital organ. Specific IgA antibodies in the lumen are capable of reducing infection by impairing or blocking penetration of the host tissue by the pathogen. Mechanisms known to underly the inhibition of host tissue penetration include: the neutralization of viruses; the complexation with enzymes, toxins or other components produced by the pathogens (resulting in either neutralization of the activity of these components and/or blocking the adsorption of these components); the inhibition of adherence of the pathogens to mucosal surfaces; the suppression of antibody mediated inflammnatory reactions at the mucosal surfaces; and synergism with innate antibacterial factors at the musocal surface.
Mucosal (nonparenteral) vaccines and mucosal vaccination have other additional advantages over parenteral vaccines and parenteral vaccination. These advantages include the elimination of the need to breach the integrity of the skin, tissues or organs of the host, ease of administration, the possibility of employing a low grade of purity, establishment of immunity at the site of natural infection, prevention of penetration of the host tissue by the pathogen, more complete protection of the organism against both clinical and nonclinical symptoms of the infection as well as the infection itself, protection against latency and concomitant induction of mucosal and systemic immunity. Furthermore, mucosal vaccines and mucosal vaccination permit the effective immunization of immunocompromised hosts (i.e., young animals with maternal antibodies).
Thus, it can be seen that, in many cases the use of mucosal (nonparenteral) vaccines, mucosal vaccination and the immunity provided thereby is preferable over the use of parenteral vaccines, parenteral vaccination and the immunity provided thereby.
Depending on various factors, natural or artificial infection with live microorganisms can induce considerable levels of mucosal immunity. These factors include: the route of infection, the nature of the microorganism, the infectious dose involved and the immune status of the host.
However, the administration of killed (non-replicating) antigens gives little or no mucosal immunity. To alleviate this problem, adjuvants are used to increase the immune responses to killed antigens.
The adequate induction of mucosal immunity with killed (non-replicating) antigens requires both the administration of antigen to the mucosae and the use of appropriate adjuvants or antigen presentation systems.
While numerous adjuvants for parenteral vaccines are known, only a few have been shown to be useful in enhancing mucosal immunity. Such adjuvants include the toxin of
Vibrio cholera
(Cholera toxin) or products thereof (Cholera toxin subunit B—CTB), the heat-labile toxin of
E. coli
or products thereof, bacterial toxins or products thereof which are conjugated to antigens, microparticles or microcapsules of different natural or synthetic polymers having antigens incorporated therein, liposomes antigen incorporated therein or liposomes mixed with antigen, lectins, immunostimnulating complexes, muramyldipeptide and derivatives thereof, and cationic polymers (see, “Novel Delivery Systems for Oral Vaccines”, CRC Press, London, 1994).
Although well-known, the use of known mucosal adjuvants has been limited. This has been due to several factors, including: the unacceptable risks associated with the detrimental side effects of such adjuvants; problems of insufficient efficacy; the (partial) denaturation of antigens resulting from mechanical and/or chemical treatments which are involved in their preparation procedure; complicated production procedures which are associated therewith; the inconsistency of the production thereof, the high costs of their production; specific immune responses elicited to the adjuvant component; the instability of the adjuvant or the vaccine containing the adjuvant; and the enhancement or activation of nonspecific immune reactions which results from the use thereof.
Thus it can be seen that there remains an urgent need for adjuvants for mucosal vaccines (and, in particular for mucosal vaccines against respiratory diseases, gastro-intestinal diseases and sexually-transmissible diseases) which are safe, inexpensive, easy to produce and to incorporate into mucosal vaccines.
It is a primary object of the present invention to provide mucosal adjuvants capable of inducing or enhancing immune responses to antigens.
It is a further primary object of the present invention to provide mucosal adjuvants for mucosal vaccines (and, in particular, for mucosal vaccines against respiratory diseases, gastro-intestinal diseases and sexually-transmissible diseases) which are safe, inexpensive, easy to produce and easy to incorporate in to such mucosal vaccines in which they are to be employed.
It is a still further primary object of the present invention to provide mucosal vaccines which incorporate such mucosal adjuvants therein for inducing or enhancing immune responses to antigens.
It is a yet further primary object of the present invention to provide methods for inducing or enhancing immune responses to antigens and to provide methods for providing mucosal adjuvants and mucosal vaccines comprised of mucosal adjuvants which are capable of such inducement or enhancement.
The present invention relates to mucosal adjuvants for incorporation into mucosal vaccines and to mucosal vaccines incorporating such adjuvants therein useful for the induction or enhancement of mucosal and/or systemic immune responses to antigens.
Thus, in accordance with the teachings of the present invention, there is provided a mucosal adjuvant for vaccines comprising a water-soluble polyanionic polymer having anionic constitutional repeating units.
The mucosal adjuvants of the present invent
American Cyanamid Company
Krass Frederick
Levis John F.
Mandel Adley F.
Ostrup Clinton
LandOfFree
Polyanionic polymers as adjuvants for mucosal immunization does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polyanionic polymers as adjuvants for mucosal immunization, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polyanionic polymers as adjuvants for mucosal immunization will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3091386