Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.
Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine.
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Gary R
GR
Matyas
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Bethesda, MD 20892-9415, USA; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Kenner C
KC
Rice
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Bethesda, MD 20892-9415, USA; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Kejun
K
Cheng
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Bethesda, MD 20892-9415, USA; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Fuying
F
Li
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Bethesda, MD 20892-9415, USA; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Joshua F G
JF
Antoline
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Malliga R
MR
Iyer
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, 5625 Fishers Lane, Bethesda, MD 20892-9415, USA; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 4N03, Bethesda, MD 20892-9415, USA.
Arthur E
AE
Jacobson
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817 USA.
Alexander V
AV
Mayorov
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817 USA.
Zoltan
Z
Beck
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA; U.S. Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817 USA.
Oscar B
OB
Torres
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: calving@hivresearch.org.
Carl R
CR
Alving
D000818:Animals; D000918:Antibody Specificity; D003429:Cross Reactions / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology*; D003932:Heroin / Q000276:immunology; D006556:Heroin Dependence / Q000517:prevention & control*; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000276:immunology; D009022:Morphine Derivatives / Q000276:immunology; D059225:Nociception / Q000187:drug effects; D014612:Vaccines / Q000276:immunology*
D006241:Haptens; D008050:Lipid A; D008081:Liposomes; D009022:Morphine Derivatives; D014612:Vaccines; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine; C048436:monophosphoryl lipid A
6-Acetylmorphine; Haptens; Heroin; Liposomes; Monophosphoryl lipid A; Morphine; Tetanus toxoid; Type 1 and type 2 cross-reactivity; Vaccines to drugs of abuse