Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Combination of antigens from multiple bacterial species
Reexamination Certificate
1995-03-29
2004-06-01
Smith, Lynette R. F. (Department: 1645)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Combination of antigens from multiple bacterial species
C424S093300, C424S093410, C424S130100, C424S156100, C424S163100, C424S167100, C424S184100, C424S201100, C424S239100, C424S247100, C424S255100, C424S282100
Reexamination Certificate
active
06743430
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to low dose multicomponent vaccines. More specifically, the invention relates to low dose multicomponent vaccines comprising a safe and immunogenically effective combination of: at least one protective antigen component from clostridial organisms, at least one protective antigen component from a non-clostridial organism and an adjuvant.
2. Brief Description of the Prior Art
Preparation and formulation of multicomponent vaccines have historically been complicated by physical and technological hurdles. Multicomponent vaccines of interest are those vaccines that contain as essential antigen components: one or more protective antigens from one or more organisms and an adjuvant. The protective antigen component can be in the form of a whole bacterial culture, a whole virus culture, a cell-free toxoid, a purified toxoid, or a subunit.
When one combines whole cultures of organisms (viruses or bacteria) in a formulation of multicomponent vaccines, the formulation would contain numerous antigens (hundreds to thousands). Some of these are protective antigens as mentioned above. Some of these antigens are detrimental to protection of the animals or cause reaction in the animals (“detrimental antigens”). The detrimental antigens can interfere with the protective antigens by either physically or chemically blocking the active sites of the protective antigens. The interference prevents the protective antigens from protecting animals. Also, the detrimental antigens can produce negative responses such as local reactions, systemic reactions, anaphylaxis and/or immunosuppression in the animals. Therefore, the use of combinations of whole culture organisms can cause problems with efficacy or with animal reactivity. Animal reactivity produces localized reactions resulting in swellings or abscesses at the injection sites or a systemic response such as anaphylaxis that can result in death of the animal.
Aggravating the animal reactivity is the administration of multi-component vaccines to large animals (e.g., cattle) in high doses. The dose range has historically been from about 5 mL to 10 mL to allow incorporation of all of the protective antigens into one formulation. Illustratively, up to seven clostridial whole cultures or toxoids can be combined into a 5.0 mL dose of vaccine for administration to cattle. See, for instance, pages 319, 320, 321, 322, and 432 of the Compendium of Veterinary Products, Third Edition, 1995-1996). Also, 6 Clostridial whole cultures or toxoids have been combined with
Hemophilus somnus
in a 5.0 mL dose vaccines. See pages 191, 192, 319, 433, 490, and 1013 of the Compendium of Veterinary Products, Third Edition, 1995-1996). Reportedly, such vaccines demonstrate significant animal reactivity.
Animal reactivity that produces localized reactions (often called injection site lesions or blemishes) have become a matter of significant concern for the beef industry. Many scientific and lay articles since 1991 have addressed the concern with injection site lesions. See Stokka et al, J. Am. Vet. Med. Assoc., 1994, Feb. 1, 204(3): 415-9, Effertz, Beef Today, March 1991 and Beef Today, September 1992, Dittmer, CALF News Cattle Feeder, September 1992; Smith, FEEDSTUFFS, Aug. 24, 1992, and Hrehocik et al, dvm, September 1992. During the past several years, many scientific and lay articles have reported that injection site lesions are deleterious to the quality of beef. The injection site lesions must be cut out of the meat and discarded. This causes significant monetary loses to retailers, beef packers and feedlots. It has been estimated that 12-15% of prime beef cuts have some type of injection site lesion that must be trimmed away (Effertz, Beef Today, March 1991). This article attributes the main cause of the injection site lesions to 7-way clostridial vaccines. Additionally, there have been reports that up to 90% of cattle have injection site lesions in their carcass. Injection site lesions have been associated with: (1) the presence of many detrimental antigens or contaminants which are present in whole culture vaccines, (2) the adjuvants incorporated into such vaccines, (3) the method of administration of such vaccines (4) the large dose size of some of the multicomponent vaccines (5.0-10.0 mL), and (5) animal the reactivity of the protective antigen components of the vaccines.
Typically, clostridial vaccines are not highly purified because purification can be cost prohibitive. As one would realize, animal vaccine production must be necessarily economically effective if the vaccines are to enjoy widespread use. Therefore, highly purified animal vaccines are virtually cost prohibitive.
Somewhat related prior art involves two vaccines containing six clostridial whole cultures or toxoids administered in a 2.0 mL dose volume. See Compendium of Veterinary Products, Third Edition, 1995-1996, pages 133, 1183, 1184 and 1185 and the advertising brochure entitled “ALPHA-7™-JUST ONCE”. However, these vaccines do not include any additional component such as: additional clostridial component(s) or one or more non-clostridial component(s).
Antigenic components of clostridial vaccines were typically obtained by concentrating whole cultures of the bacteria. Concentration was accomplished by precipitating whole cultures with ammonium salts such as ammonium sulfate or concentrating such whole cultures via ultrafiltration. Both procedures are costly. Additionally, these procedures produce massive amounts of cells resulting in a high antigen mass that remains as an antigenic mass of solids in the product. Such a high antigenic mass would induce animal reactivity, particularly injection site lesions.
An even greater problem exists when one combines clostridial organisms with non-clostridial organisms such as Gram-negative bacteria, e.g.,
H. somnus
and
M. bovis
and the Pasteurella spp. Many of these organisms are, in themselves, highly reactive and contain high levels of endotoxin that produce anaphylaxis. Also, their antigenic components supposedly cause interference. The high dose of the art-known combination of
H. somnus
and six clostridial components, i.e., a 5.0 mL dose volume can be the source of animal reactivity. In the case of non-clostridial viral formulations, the addition of clostridial components to these formulations can adversely affect viral epitopes. Consequently the viral components of the formulation may become non-efficacious.
Because of the severity of the Clostridial diseases and other disease complexes described herein, it is increasingly important that calves and young cattle entering feedlots as well as pregnant cows are properly vaccinated. The vaccines must contain protective antigens described herein. While one could administer each of the protective antigens in a monovalent vaccine, this mode of administration would require several vaccinations for each animal. This is impractical in a because: 1) handling animals for repeated vaccinations can result in undue stress and consequential diseases; 2) labor for performing such vaccinations is expensive compared to the profit obtained from each animal; 3) the more injection sites on an animal, the more potential for injection site reactions.
There is, therefore, a clear need for multicomponent vaccines containing many protective antigens that do not contain detrimental antigens and do not produce animal reactivity. By this invention, there are provided low dose multicomponent vaccines containing: protective antigen components of a clostridial organism(s) and at least one non-clostridial protective antigen component and an adjuvant, and the processes for making and using the vaccines.
SUMMARY OF THE INVENTION
This invention relates to a multicomponent vaccine comprising: a safe and immunogenically effective combination of protective antigen components from at least one clostridial organism, a protective antigen component from a non-clostridial organism and an adjuvant, wherein the vaccine is in a low dose volume. By “low dose” is meant
Bryant Sharon A.
McGinley Michael J.
Nibbelink Stuart K.
Parizek Richard E.
Vlieger Lonny E.
Blackstone William M.
Hines Ja'Na
Ramey III William P.
Smith Lynette R. F.
LandOfFree
Multicomponent vaccine containing clostridial and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Multicomponent vaccine containing clostridial and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Multicomponent vaccine containing clostridial and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3326706