A bioconjugate leveraging xenoreactive antibodies to alleviate cocaine-induced behavior

Jacob, Nicholas T.; Anraku, Kensaku; Kimishima, Atsushi; Zhou, Bin; Collins, Karen; Lockner, Jonathan W.; Ellis, Beverly A.; Janda, Kim D.

doi:10.1039/c7cc04055e

Cited by 6 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within the GC, CD4 + T helper (Th) cells will also differentiate into Th 1 , Th 2 , Th 17 , T follicular helper (T fh ), and GC-T fh subsets which coordinate B cell responses to different antigens 27,28 . In this context, B and T cell responses to vaccines can be shaped by the incorporation of adjuvants to achieve successful immunization 29,30 . Pre-clinical studies have already shown that the efficacy of vaccines against SUD is enhanced by adjuvants such as aluminum salts (alum) and toll-like receptor 4 (TLR4) or TLR9 agonists [31][32][33][34] .…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

et al. 2020

View full text Add to dashboard Cite

Opioid use disorders (OUD) affect over 27 million people worldwide. Anti-opioid vaccines offer a promising strategy to treat OUD and prevent overdose. Using immunomodulation of cytokine signaling to increase vaccine efficacy, this study found that blocking IL-4 improved the efficacy of vaccines targeting oxycodone and fentanyl in male and female mice. Genetic deletion of the IL-4 receptor, STAT6, or antibody-based depletion of IL-13, did not increase vaccine efficacy against opioids, suggesting the involvement of type I IL-4 receptors. Enhancement of vaccine efficacy with blockade of IL-4 was associated with improved germinal center formation in secondary lymphoid organs and selective transcriptome signatures in the activated CD4+ T cell population subset. These data suggest that IL-4 is both a pharmacological target and a potential biomarker of vaccine efficacy against OUD.

show abstract

Section: Introductionmentioning

confidence: 99%

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Enhanced antigen uptake and presentation by antigen-presenting cells was achieved by targeting the Fcγ receptor (FcγR) stimulating the release of cytokines for the recruitment of effector cells (e.g., CD4 + T cells). In this study, anti-cocaine vaccines GNE -OVA-GAL (and GNE -TT-GAL; Table ) formulated with alhydrogel effectively produced a viable anti-cocaine response . This xenoreactive antibody vaccination strategy led to an antibody response with higher affinity for cocaine that significantly attenuated cocaine-induced locomotion.…”

Section: Anti-cocaine Vaccinesmentioning

confidence: 99%

“…Janda and co-workers devised a method for enhancing the response to cocaine haptens through conjugation of a carbohydrate epitope (e.g., Galα1,3-Gal, GAL), leading to a highly specific anti-cocaine vaccine that significantly attenuated cocaine-induced locomotion compared to the hapten−carrier protein alone. 51 Enhanced antigen uptake and presentation by antigen-presenting cells was achieved by targeting the Fcγ receptor (FcγR) stimulating the release of cytokines for the recruitment of effector cells (e.g., CD4 + T cells). In this study, anti-cocaine vaccines GNE-OVA-GAL (and GNE-TT-GAL; Table 1) formulated with alhydrogel effectively produced a viable anti-cocaine response.…”

Section: Pre-clinical Advances Inmentioning

confidence: 99%

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Stephenson

Tóth

2023

J. Med. Chem.

View full text Add to dashboard Cite

Cocaine is one of the oldest and most widely used illicit drugs in the world and is responsible for major worldwide medical and social problems. Drug addiction is a disease state where the body relies on a substance for normal functioning and develops a physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state, or social life. The primary driver for the development of anti-cocaine vaccines has been the failure to develop effective pharmacological treatments to combat cocaine dependence. Despite several decades of research, no approved pharmacological treatments for cocaine dependence are available to assist addicts to overcome cocaine withdrawal or to prevent drug relapse. This Perspective highlights the challenges associated with anti-cocaine vaccines, including the current state of anti-cocaine vaccines and catalytic antibody research to aid in the fight against cocaine addiction.

show abstract

“…Antidrug vaccines targeting multiple, structurally distinct species are not common and have utilized two tactics: 1) mixing two individual vaccines together (admixture vaccine) [9–10]; or 2) successive conjugation steps of one hapten and then the second to a carrier protein [11–12]. To specifically address the escalating incidence of fentanyl-contamination in heroin, we investigated the efficacy of an admixture of individual heroin and fentanyl conjugate vaccines against challenges of 10–20% fentanyl in heroin [13–14].…”

Section: Introductionmentioning

confidence: 99%

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

Natori¹,

Hwang

Lin

et al. 2019

Beilstein J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

Background: Increased death due to the opioid epidemic in the United States has necessitated the development of new strategies to treat addiction. Monoclonal antibodies and antidrug vaccines provide a tool that both aids addiction management and reduces the potential for overdose. Dual drug vaccines formulated by successive conjugation or by mixture have certain drawbacks. The current study examines an approach for combatting the dangers of fentanyl-laced heroin, by using a hapten with one epitope that has domains for both fentanyl and heroin. Results: We evaluated a series of nine vaccines developed from chemically contiguous haptens composed of both heroin- and fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark heroin vaccine, but exhibited attenuated protection against fentanyl compared to our fentanyl vaccine. Conclusion: After thorough investigation of this strategy, we have identified key considerations for the development of a chemically contiguous heroin–fentanyl vaccine. Importantly, this is the first report of such a strategy in the opioid–drug–vaccine field.

show abstract

A bioconjugate leveraging xenoreactive antibodies to alleviate cocaine-induced behavior

Cited by 6 publications

References 32 publications

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

Mechanisms of interleukin 4 mediated increase in efficacy of vaccines against opioid use disorders

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

Contact Info

Product

Resources

About