Flagellin-based agents and uses including effective vaccination

Abstract

The present invention relates to, in part, compositions comprising improved flagellin derived constructs and methods of using for vaccination, including adjuvants comprising flagellin-based agents.

1 .- 24 . (canceled) 
     
     
         25 . A method of vaccinating a subject against a substance abuse disorder, comprising administering an effective amount of a vaccine comprising:
 (a) an adjuvant comprising:
 a flagellin-based agent comprising an amino acid sequence having at least 95% identity with SEQ ID NO: 2, and an aluminum gel or salt, 
 wherein the ratio (w/w) of flagellin-based agent to aluminum gel or salt is about 1:500 or less and 
   (b) an antigen, the antigen being a constituent of an infectious agent selected from a live and attenuated, killed, inactivated or toxoid, infectious agent.   
     
     
         26 . The method of  claim 25 , wherein the substance abuse disorder is addiction to one or more of fentanyl, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), heroin, morphine, opium, oxycodone, hydrocodone, ketamine, phencyclidine (PCP), barbiturates, benzodiazepines, flunitrazepam, γ-hydroxybutyric acid (GHB), methaqualone, hashish, marijuana, lysergic acid diethylamide (LSD), mescaline, psilocybin, amphetamine, cocaine, methylphenidate, and nicotine. 
     
     
         27 . The method of  claim 26 , wherein the substance abuse disorder is addiction to methamphetamine. 
     
     
         28 . The method of  claim 26 , wherein the substance abuse disorder is addiction to fentanyl. 
     
     
         29 . The method of  claim 25 , wherein the antigen is the antigen of any one of the following vaccines: DTP (diphtheria-tetanus-pertussis vaccine), DTaP (diphtheria-tetanus-acellular pertussis vaccine), Hib ( Haemophilus influenzae  type b) conjugate vaccines, Pneumococcal conjugate vaccine, Hepatitis A vaccines, Poliomyelitis vaccines, Yellow fever vaccines, Hepatitis B vaccines, combination DTaP, Tdap, Hib, Human Papillomavirus (HPV) vaccine, Anthrax vaccine, and Rabies vaccine. 
     
     
         30 . The method of  claim 25 , wherein the antigen further comprises of any one of fentanyl, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), heroin, morphine, opium, oxycodone, hydrocodone, ketamine, phencyclidine (PCP), barbiturates, benzodiazepines, flunitrazepam, γ-hydroxybutyric acid (GHB), methaqualone, hashish, marijuana, lysergic acid diethylamide (LSD), mescaline, psilocybin, amphetamine, cocaine, methylphenidate, and nicotine. 
     
     
         31 . The method of  claim 25 , wherein the antigen is diphtheria antigen. 
     
     
         32 . The method of  claim 25 , wherein the antigen is tetanus antigen. 
     
     
         33 . The method of  claim 25 , wherein the flagellin-based agent comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         34 . The method of  claim 25 , wherein the flagellin-based agent comprises the amino acid sequence of SEQ ID NO: 2 and the antigen comprises succinyl methamphetamine (SMA) hapten conjugated to tetanus toxoid. 
     
     
         35 . The method of  claim 25 , wherein the flagellin-based agent inhibits and abrogates the ability of neutralizing anti-flagellin antibodies to neutralize the adjuvant. 
     
     
         36 . The method of  claim 25 , wherein the aluminum gel or salt is selected from aluminum hydroxide, aluminum phosphate, and aluminum sulfate. 
     
     
         37 . The method of  claim 25 , wherein the flagellin-based agent and/or antigen is adsorbed to the aluminum gel or salt. 
     
     
         38 . The method of  claim 25 , wherein one or more of the flagellin-based agent and aluminum gel or salt are mixed to form a stable complex. 
     
     
         39 . The method of  claim 25 , wherein the flagellin-based agent and aluminum gel or salt are mixed in a ratio that is substantially below a loading capacity of the aluminum salt. 
     
     
         40 . The method of  claim 38 , wherein the flagellin-based agent and aluminum gel or salt are mixed in a ratio (w/w) of about 1:500, or about 1:600, or about 1:700, or about 1:800, or about 1:900, or about 1:1000, or about 1:2000, or about 1:5000, or about 1:10000. 
     
     
         41 . The method of  claim 25 , wherein the vaccine further comprises an additional adjuvant selected from oil-in-water emulsion formulations, saponin adjuvants, ovalbumin, Freund's Adjuvant, cytokines, and chitosans. 
     
     
         42 . The method of  claim 25 , wherein the vaccine and/or adjuvant causes immunostimulation of one or more of a T H1  and T H2 -mediated immune response. 
     
     
         43 . The method of  claim 25 , wherein the administering is orally or by parenteral injection. 
     
     
         44 . The method of  claim 25 , wherein the administering takes place by controlled-release or sustained-release. 
     
     
         45 . The method of  claim 25 , wherein the vaccine is administered once per subject or is used in a booster strategy.