Drug – bio-affecting and body treating compositions – Nonspecific immunoeffector – per se ; or nonspecific... – Synthetic or structurally-modified peptidoglycan or...
Reexamination Certificate
1997-11-07
2001-05-01
Eyler, Yvonne (Department: 1642)
Drug, bio-affecting and body treating compositions
Nonspecific immunoeffector, per se ; or nonspecific...
Synthetic or structurally-modified peptidoglycan or...
C424S278100, C424S093100, C424S184100
Reexamination Certificate
active
06224882
ABSTRACT:
FIELD OF THE INVENTION
The present invention pertains to adjuvants, such as adjuvants for at least one epitope of interest or antigen (including allergen), immunological, immunogenic, antigenic or vaccine compositions comprising the adjuvants, and methods for making and using the same. More in particular, the present invention relates to insect cells or fractions thereof as adjuvants, such as adjuvants for at least one epitope of interest or antigen (including allergen), immunological, immunogenic, antigenic or vaccine compositions comprising the adjuvants, and methods for making and using the same.
The present invention also relates to insect cells or fractions thereof, e.g., Lepidopteran insect species insect cells or fractions thereof such as
S. frugiperda
insect cells or fractions thereof, preferably obtainable from infection with an insect virus such as a baculovirus, e.g., a recombinant insect virus such as a recombinant baculovirus, comprising adjuvants, such as adjuvants for at least one epitope of interest or antigen (including allergen), immunological, immunogenic, antigenic or vaccine compositions comprising the adjuvants, and methods for making and using the same.
The at least one epitope of interest or antigen can be a recombinant protein from expression of the recombinant baculovirus. Thus, the invention advantageously pertains to an adjuvant comprising insect cells or fractions thereof, e.g., Lepidopteran insect species insect cells or fractions thereof such as
S. frugiperda
insect cells or fractions thereof, from infection with a recombinant insect virus such as a recombinant baculovirus, for enhancing the immunogenicity of at least one epitope of interest or antigen (including allergen), to an immunological, immunogenic, antigenic or vaccine composition comprising the adjuvant and the at least one epitope of interest or antigen; wherein, advantageously the epitope of interest or antigen is from expression of at least one exogenous coding nucleic acid therefor by the recombinant virus from infection of the cells by the recombinant virus; and, to methods for making and using the same.
The inventive adjuvants surprisingly favorably alter the immune response by a vertebrate, e.g., avian, mammal, to the epitope of interest or antigen combined therewith. And, the invention pertains to compositions, uses and methods arising from this observation.
Several publications are referenced in this application, either at the end of the specification immediately preceding the claims or where the publication is mentioned; and each of these publications and each of the documents cited in each of these publications is hereby incorporated herein by reference. There is no admission that any of these publications are indeed prior art with respect to the present invention.
BACKGROUND OF THE INVENTION
Immunogenicity can be significantly improved if an antigen is co-administered with an adjuvant, commonly used as 0.001% to 50% solution in phosphate buffered saline. Adjuvants are substances that enhance the immune response to antigens, but are not necessarily immunogenic themselves. Adjuvants may act by retaining the antigen locally near the site of administration to produce a depot effect facilitating a slow, sustained release of antigen to cells of the immune system. Adjuvants can also attract cells of the immune system to an antigen depot and stimulate such cells to elicit immune responses.
Immunostimulatory agents or adjuvants have been used for many years to improve the host immune response to, for example, vaccines. Intrinsic adjuvants, such as lipopolysaccarides, normally are the components of the killed or attenuated bacteria used as vaccines. Extrinsic adjuvants are immunomodulators which are typically non-covalently linked to antigens and are formulated to enhance the host immune response.
Aluminum hydroxide and aluminum phosphate (collectively commonly referred to as alum) are routinely used as adjuvants in human and veterinary vaccines. The efficacy of alum in increasing antibody responses to diphtheria and tetanus toxoids is well established and, more recently, a HBsAg vaccine has been adjuvanted with alum.
A wide range of extrinsic adjuvants can provoke potent immune responses to antigens. These include saponins complexed to membrane protein antigens (immune stimulating complexes), pluronic polymers with mineral oil, killed mycobacteria in mineral oil, Freund's complete adjuvant, bacterial products, such as muramyl dipeptide (MDP) and lipopolysaccharide (LPS), as well as lipid A, and liposomes. To efficiently induce humoral immune response (HIR) and cell-mediated immunity (CMI), immunogens are preferably emulsified in adjuvants.
Chemically defined adjuvants, such as monophosphoryl lipid A, phospholipid conjugates have been investigated (see Goodman-Snitkoff et al., J. Immunol. 147:410-415 (1991)) as has encapsulation of the protein within a proteoliposome (see Miller et al., J. Exp. Med. 176:1739-1744 (1992)).
Synthetic polymers have also been evaluated as adjuvants. These include the homo- and copolymers of lactic and glycolic acid, which have been used to produce microspheres that encapsulate antigens (see Eldridge et al., Mol. Immunol. 28:287-294 (1993)).
Nonionic block copolymers are another synthetic adjuvant being evaluated. Adjuvant effects have also been investigated for low molecular weight copolymers in oil-based emulsions (see Hunter et al., The Theory and Practical Application of Adjuvants (Ed. Stewart-Tull, D. E. S.). John Wiley and Sons, N.Y., pp51-94 (1995)) and for high molecular weight copolymers in aqueous formulations (Todd et al., Vaccine 15:564-570 (1997)).
Desirable characteristics of ideal adjuvants include any or all (preferably most and most preferably all) of:
(1) lack of toxicity;
(2) ability to stimulate a long-lasting immune response;
(3) simplicity of manufacture and stability in long-term storage;
(4) ability to elicit both CMI and HIR to antigens administered by various routes;
(5) synergy with other adjuvants;
(6) capability of selectively interacting with populations of antigen presenting cells (APC);
(7) ability to specifically elicit appropriate T
H
1 or T
H
2 cell-specific immune responses; and
(8) ability to selectively increase appropriate antibody isotype levels (for example IgA) against antigens.
At this time however, the only adjuvant widely used in humans has been alum. Other adjuvants, such as Sponin, Quil A, and the water-in-oil adjuvant, Freund's with killed tubercle bacilli (Freund's complete) or without bacilli (Freund's incomplete), have had limited use in humans due to their toxic effects; and, concerns have been raised as to undesirable effects in animals. Simply, many adjuvant formulations have been described but most are never accepted for routine vaccines, and few have been evaluated in humans, mainly due to their toxicity.
For example, the mineral oils used as adjuvants in certain animal vaccines are not readily degraded and persist at the site of injection thereby causing unacceptable granulomas; and, in general adjuvant formulations such as mineral compounds oil emulsions, liposomes and biodegradable polymer microspheres cause local reactions due to depot formation at the site of injection.
In fact, the adjuvant effect of most experimental adjuvants has been associated with the adverse effects they elicit.
For instance, adjuvants that act as immunostimulators such as muramyl dipeptide, lipopolysaccaride, lipid A, monophosphoryl lipid A, and cytokines such as IL-2 and IL-12 can also cause systemic side-effects (general toxicity, pyrogenicity), limiting their use.
Accordingly, a problem in the art is a need for adjuvants. There remains a need for improved adjuvants that are safe and economical to manufacture for human and veterinary vaccines (reviewed by Gupta and Siber, Vaccine 13:1263-1276 (1995)).
Insect cells from
S. frugiperda
and other Lepidopteran insect species have been described in the literature and their general use to support the infection and replication of baculoviruses and the
DeBartolomeis James
Smith Gale Eugene
Voznesenski Andrei Igorevitch
Eyler Yvonne
Frommer & Lawrence & Haug LLP
Kowalski Thomas J.
Protein Science Corp.
Sun-Hoffman Lin
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