In recognition of the frequent association of HIV-1 infection with the use of injected heroin, the US Military HIV Research Program (MHRP) and the National Institute for Drug Abuse initiated a collaborative interagency agreement in 2010 to examine the feasibility of creating a practical combination anti-heroin vaccine (AHV) and HIV vaccine product. Based on the recent multi- institutional immune correlate analyses of the successful MHRP RV144 Thai trial that demonstrated that antibodies directed to the HIV-1 gp120 V2 loop correlated with protection against HIV-1 infection, together with previous studies that demonstrated the feasibility of immunoprotection to heroin abuse, MHRP believes that a unique opportunity exists to create a candidate peptide vaccine both to HIV-1 and heroin. As a result of this collaboration, a safe, inexpensive, heroin-hapten-peptide-based, easily manufactured, strongly adjuvanted combination candidate AHV/HIV vaccine product has now been created that is ready for optimization and advanced preclinical testing for anticipated phase I and phase II clinical trials. If successful it is anticipated that this vaccine will provid a deployable heroin vaccine and will represent a major advance for creation of a practical and effective HIV vaccine. The major goals are to: (1) optimize the hapten-gp41/gp120-T helper peptide-adjuvant-carrier formulation by examining the relative immune responses in rodents with three alternative identified lead heroin haptens;(2) perform advanced preclinical immunogenicity studies in rodents with the final lead formulation to examine antibody isotypes, affinities, specificities for heroin and HIV gp41 and gp120-V2 loop epitopes;(3) examine vaccine-induced anti-heroin antibodies for prevention of anesthetic effects and prevention of physiological effects associated with drug overdose in rodents and non-human primates;(4) perform neutralization and other in vitro functional analyses of vaccine- i

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
NIH Director’s Pioneer Award (NDPA) (DP1)
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Special Emphasis Panel (ZDA1-SXC-E (06))
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Chiang, Nora
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Henry M. Jackson Fdn for the Adv Mil/Med
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Torres, Oscar B; Antoline, Joshua F G; Li, Fuying et al. (2016) A simple nonradioactive method for the determination of the binding affinities of antibodies induced by hapten bioconjugates for drugs of abuse. Anal Bioanal Chem 408:1191-204
Torres, Oscar B; Alving, Carl R; Matyas, Gary R (2016) Synthesis of Hapten-Protein Conjugate Vaccines with Reproducible Hapten Densities. Methods Mol Biol 1403:695-710
Jalah, Rashmi; Torres, Oscar B; Mayorov, Alexander V et al. (2015) Efficacy, but not antibody titer or affinity, of a heroin hapten conjugate vaccine correlates with increasing hapten densities on tetanus toxoid, but not on CRM197 carriers. Bioconjug Chem 26:1041-53
Alving, Carl R; Matyas, Gary R; Torres, Oscar et al. (2014) Adjuvants for vaccines to drugs of abuse and addiction. Vaccine 32:5382-9
Torres, Oscar B; Jalah, Rashmi; Rice, Kenner C et al. (2014) Characterization and optimization of heroin hapten-BSA conjugates: method development for the synthesis of reproducible hapten-based vaccines. Anal Bioanal Chem 406:5927-37
Matyas, Gary R; Rice, Kenner C; Cheng, Kejun et al. (2014) Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine. Vaccine 32:1473-9
Li, Fuying; Cheng, Kejun; Antoline, Joshua F G et al. (2014) Synthesis and immunological effects of heroin vaccines. Org Biomol Chem 12:7211-32
Matyas, Gary R; Mayorov, Alexander V; Rice, Kenner C et al. (2013) Liposomes containing monophosphoryl lipid A: a potent adjuvant system for inducing antibodies to heroin hapten analogs. Vaccine 31:2804-10