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

Public Health Relevance

The practical outcome of this research will identify a practical, relatively inexpensive, and easily manufactured combination vaccine that could potentially be deployed both for therapy of heroin drug abuse and for prevention of HIV infection. The vaccine research in this project will have completed essentially all of the preclinical steps required for presentation to the US Food and Drug Administration, and for subsequent human clinical trials to test safety and efficacy in heroin users, and for those at risk for HIV infection. The proposed vaccine, if successful in advanced clinical trials and approved for human use, could directly enter medical practice for therapy of heroin injection drug users, with the expectation of reduction or elimination of the heroin ?high?, reduction of the consequent risk for heroin overdose reaction, and reduction of the risk HIV infection.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1DA034787-04
Application #
8904645
Study Section
Special Emphasis Panel (ZDA1)
Program Officer
Chiang, Nora
Project Start
2012-08-01
Project End
2016-07-31
Budget Start
2015-08-01
Budget End
2016-07-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
144676566
City
Bethesda
State
MD
Country
United States
Zip Code
20817
Sulima, Agnieszka; Jalah, Rashmi; Antoline, Joshua F G et al. (2018) A Stable Heroin Analogue That Can Serve as a Vaccine Hapten to Induce Antibodies That Block the Effects of Heroin and Its Metabolites in Rodents and That Cross-React Immunologically with Related Drugs of Abuse. J Med Chem 61:329-343
Beck, Zoltan; Torres, Oscar B; Matyas, Gary R et al. (2018) Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex. J Control Release 275:12-19
Torres, Oscar B; Matyas, Gary R; Rao, Mangala et al. (2017) Heroin-HIV-1 (H2) vaccine: induction of dual immunologic effects with a heroin hapten-conjugate and an HIV-1 envelope V2 peptide with liposomal lipid A as an adjuvant. NPJ Vaccines 2:13
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
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
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; 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
Alving, Carl R; Matyas, Gary R; Torres, Oscar et al. (2014) Adjuvants for vaccines to drugs of abuse and addiction. Vaccine 32:5382-9

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