Effect of Preexisting Immunity to Tetanus Toxoid on the Efficacy of Tetanus Toxoid-Conjugated Heroin Vaccine in Mice
Essie Komla,
Oscar B. Torres,
Rashmi Jalah,
Agnieszka Sulima,
Zoltan Beck,
Carl R. Alving,
Arthur E. Jacobson,
Kenner C. Rice,
Gary R. Matyas
Affiliations
Essie Komla
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
Oscar B. 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
Rashmi Jalah
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
Agnieszka Sulima
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3373, USA
Zoltan 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
Carl R. Alving
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
Arthur E. Jacobson
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3373, USA
Kenner C. Rice
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 9800 Medical Center Drive, Bethesda, MD 20892-3373, USA
Gary R. Matyas
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
Opioid use disorder (OUD) is a serious health problem that has dramatically increased over the last decade. Although current therapies for the management of OUD can be effective, they have limitations. The complementary strategy to combat the opioid crisis is the development of a conjugate vaccine to generate high affinity antibodies in order to neutralize opioids in circulation before reaching the brain. The components of an opioid vaccine include an opioid hapten (6-AmHap) that is conjugated to a carrier protein (tetanus toxoid) with the addition of adjuvants (Army Liposome Formulation adsorbed to aluminum hydroxide-ALFA). There is no consensus in the literature as to whether preexisting immunity to the carrier protein may impact the immunogenicity of the conjugate vaccine by inducing an enhanced or suppressed immune response to the hapten. Here, we investigated whether pre-exposure to tetanus toxoid would affect the immunogenicity and efficacy of the heroin vaccine, TT-6-AmHap. Mice were primed with diphtheria, tetanus, and acellular pertussis (DTaP) vaccine at weeks -4 and -2, then immunized with TT-6-AmHap vaccine at weeks 0, 3, and 6. Using ELISA and behavioral assays, we found that preexisting immunity to tetanus toxoid had no influence on the immunogenicity and efficacy of the TT-6-AmHap vaccine.
