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 vaccineinduced anti-HIV antibodies from rodents and non-human primates;and (5) demonstrate the feasibility of inexpensive scaled-up vaccine manufacture for future phase I/II clinical studies.
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.
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