Disrupted adenovirus-based vaccine against drugs of abuse
The invention is directed to an adenovirus-antigen conjugate comprising (a) a disrupted adenovirus with a coat protein and (b) an antigen conjugated to the coat protein of the disrupted adenovirus, as well as a conjugate comprising (a) a disrupted adenovirus with a coat protein and (b) an antigen conjugated to the coat protein of the disrupted adenovirus. The invention also provides a method of inducing an immune response against an antigen in a human using the aforementioned conjugates. The invention further provides an adeno-associated viral vector comprising a nucleic acid sequence which encodes an antibody directed against cocaine.
1. A method of inducing an immune response against an addictive drug in a mammal, which method comprises:
(a) preparing a replication-deficient adenovirus comprising an adenoviral genome except for all or part of the E1A region, all or part of the E1B region, and all or part of the E3 region of the adenoviral genome,
(b) exposing the adenovirus to a temperature of about 50° C. to 70° C. and treating the adenovirus with sodium dodecyl sulfate (SDS) to release the nucleoprotein core and capsid proteins of the adenovirus,
(c) covalently linking an antigen of an addictive drug to one or more of the adenovirus capsid proteins to produce an adenovirus-antigen conjugate, thereby producing a composition comprising the adenovirus nucleoprotein core and the adenovirus-antigen conjugate, wherein the composition does not contain an intact adenovirus particle, and
(d) administering the composition to a mammal, whereby the antigen is presented to the immune system of the mammal to induce an immune response against the antigen in the mammal.
2. The method of claim 1 , wherein the antigen is an addictive drug or an analog or portion thereof.
3. The method of claim 1 , wherein the antigen is a small molecule.
4. The method of claim 3 , wherein the small molecule is a hapten.
5. The method of claim 1 , wherein the one or more capsid proteins is a hexon protein, a fiber protein, or a penton base protein.
6. The method of claim 1 , wherein the capsid protein comprises at least one non-native lysine residue.
7. The method of claim 6 , wherein the capsid protein comprises 5 to 10 non-native lysine residues.
8. The method of claim 2 , wherein the addictive drug is selected from the group consisting of opioids, morphine derivatives, depressants, dissociative anesthetics, cannabinoids, hallucinogens, stimulants, prescription medications, anabolic steroids, inhalants, and club drugs.
9. The method of claim 2 , wherein the addictive drug is selected from the group consisting of cocaine, fentanyl, heroin, morphine, opium, oxycodone, hydrocodone, ketamine, phencyclidine (PCP), barbiturates, benzodiazepines, flunitrazepam, y-hydroxybutyric acid (GHB), methaqualone, hashish, marijuana, lysergic acid diethylamide (LSD), mescaline, psilocybin, amphetamine, 3.4-Methylenedioxymethamphetamine (MDMA), methamphetamine, methylphenidate, and nicotine.
10. The method of claim 9 , wherein the addictive drug is cocaine.
11. The method of claim 1 , wherein the antigen is 6-(2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1]octane-2-carbonyloxy-hexanoic acid (GNC) or 6-((2R,3S)-3-(benzoyloxy)-8-methyl-8-azabicyclo [3.2.1] octane-2-carboxamido)hexanoic acid) (GNE).
12. The method of claim 1 , wherein the immune response induced against the addictive drug in the mammal by administration of the composition is greater than the immune response induced in the mammal by administration of the antigen alone.
13. The method of claim 1 , wherein the replication-deficient adenovirus is a human or non-human primate adenovirus.
14. The method of claim 13 , wherein the replication-deficient adenovirus is a human serotype 5 adenovirus.
15. The method of claim 13 , wherein the adenovirus is a non-human primate serotype C7 or sAd36 adenovirus.