Heroin vaccine: Using titer, affinity, and antinociception as metrics when examining sex and strain differences

• Published in: Vaccine Vol. 37; no. 30; pp. 4155 - 4163
• Main Authors: Hwang, Candy S., Smith, Lauren C., Wenthur, Cody J., Ellis, Beverly, Zhou, Bin, Janda, Kim D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 09.07.2019; Elsevier Limited
• Subjects: Allergy and Immunology; Binding sites; Conjugate vaccine; cytokines; Drug abuse; Experiments; Females; Gender differences; genetic variation; Heroin; human population; Human populations; Hypersensitivity; Immune response; Immune system; Immunization; Immunoglobulin E; Inbreeding; Laboratory animals; Males; mice; Mouse; Narcotics; Pain perception; Quarantine; Sex; Sex differences; Sexes; Strain; strain differences; Substance use; Tetanus; vaccination; Vaccines; Women; United States > US; PBS; TT; SUD; SW; Conjugate vaccine; Sex differences; s.c; i.p; CpG ODN; Strain; BSA; Mouse; SPR; NHS; J:DO; 6-AM; Heroin; Jackson Diversity:Outbred; N-hydroxysuccinimide; subcutaneous; CpG oligodeoxynucleotides; surface plasmon resonance; Swiss Webster; 6-acetylmorphine; tetanus toxoid; intraperitoneal; substance use disorder; phosphate buffered saline; bovine serum albumin
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2019.05.061

•Heroin-TT vaccine variability was tested in both sexes in several mouse strains.•Vaccinated male SW mice exhibit rare hypersensitivity to low exposure of heroin.•Hypersensitivity is limited to male SW mice and not due to cytokine or IgE response.•Inbred BALB/c and outbred J:DO had the best response against heroin.•Vaccinated males and females of the same strain exhibit similar responses heroin. Anti-drug vaccines have potential as new interventions against substance use disorder (SUD). However, given the challenges seen with inter-individual variability in SUD vaccine trials to date, new interventions should ensure a robust immune response and safety profile among a diverse population. This requires accounting for sex and heritable genetic differences in response to both abused substances as well as the vaccination itself. To test response variability to our heroin-tetanus toxoid (Her-TT) immunoconjugate vaccine, we vaccinated male and female mice from several mouse strains including Swiss Webster (SW), BALB/c, and Jackson diversity mice (J:DO). Previous studies with vaccinated male SW mice demonstrated a rare hypersensitivity resulting in mice rapidly expiring with exposure to a low dose of heroin. Our results indicate that this response is limited to only male SW mice, and not to any other strain or female SW mice. Our data suggest that this hypersensitivity is not the result of an overactive cytokine or IgE response. Vaccination was similarly effective among the sexes for each strain and against repeated heroin challenge. Inbred BALB/c and J:DO mice were found to have the best vaccine response against heroin in antinociception behavioral assay. These results highlight the importance of incorporating both male and female subjects, along with different strains to mimic diverse human populations, as new SUD vaccines are being tested.