Abstract
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.
Highlights
Opioid use disorder (OUD) is a serious public health concern in the United States and around the world
To determine if preexisting immunity to tetanus toxoid (TT) would interfere with TT-6-AmHap immune responses, mice were primed with increasing doses of the DTaP vaccine ranging from 1/5000th dose of DTaP (0.1 μL DTaP) to 1/20th dose of DTaP (25 μL DTaP) at weeks
Following 3 doses of TT-6-AmHap, DTaP, antibody levels of TT, diphtheria toxoid (DT), and pertussis toxin (PT) were elevated for the 10 μL and 25 μL DTaP
Summary
Opioid use disorder (OUD) is a serious public health concern in the United States and around the world. In response to the opioid crisis, federal and state agencies have developed strategies to reduce the burden caused by opioid misuse through continued surveillance of medication-assisted treatment (MAT), which is the gold standard treatment for OUD [1,2,3]. Current FDA-approved medications for OUD include methadone, buprenorphine, naltrexone, in addition to naloxone, which is approved for opioid overdose reversal. These medications have been effective, their use comes with many limitations, including side effects (constipation, diarrhea, withdrawal symptoms) and compliance issues [3]. They have failed to curb the continued growth of OUD in the US. An additional strategy that may be useful to combat the opioid crisis is vaccination against opioids
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