Developing Translational Vaccines against Heroin and Fentanyl through Investigation of Adjuvants and Stability

The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small-molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal...

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Published inMolecular pharmaceutics Vol. 18; no. 1; pp. 228 - 235
Main Authors Blake, Steven, Bremer, Paul T, Zhou, Bin, Petrovsky, Nikolai, Smith, Lauren C, Hwang, Candy S, Janda, Kim D
Format Journal Article
LanguageEnglish
Published United States 04.01.2021
Subjects
Adjuvants, Immunologic - pharmacology
Adjuvants, Pharmaceutic - pharmacology
Analgesics, Opioid - immunology
Animals
Fentanyl - immunology
Heroin - immunology
Immunization - methods
Male
Mice
Mice, Inbred BALB C
Oligodeoxyribonucleotides - immunology
Opioid-Related Disorders - immunology
Vaccination - methods
Vaccines, Conjugate - immunology
vaccine
heroin
fentanyl
carrier protein
immunopharmacotherapy
adjuvants
opioids
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Abstract The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small-molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal with side effects and financial hardships from their repeated use. An alternative therapeutic approach utilizes endogenously generated antibodies through active vaccination to reduce the effect of opioids without modulating the opioid receptor. Here, we explore different adjuvants and storage conditions to improve opioid vaccine efficacy and shelf life. Our results revealed that inulin-based formulations (Advax) containing a CpG oligodeoxynucleotide (ODN) acted as effective adjuvants when combined with a heroin conjugate: immunized mice showed excellent recovery from heroin-induced antinociception accompanied by high titer, high opioid affinity serum antibodies similar to the immunopotentiating properties of traditional alum-based adjuvants. Moreover, nonhuman primates vaccinated with a heroin/fentanyl combination vaccine demonstrated potent antibody responses against opioids when formulated with both inulin and alum adjuvants. Finally, storing a freeze-dried opioid vaccine formulation maintained efficacy for up 1 year at room temperature. The results from our studies represent an advance toward a clinically feasible opioid vaccine.
AbstractList The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small-molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal with side effects and financial hardships from their repeated use. An alternative therapeutic approach utilizes endogenously generated antibodies through active vaccination to reduce the effect of opioids without modulating the opioid receptor. Here, we explore different adjuvants and storage conditions to improve opioid vaccine efficacy and shelf life. Our results revealed that inulin-based formulations (Advax) containing a CpG oligodeoxynucleotide (ODN) acted as effective adjuvants when combined with a heroin conjugate: immunized mice showed excellent recovery from heroin-induced antinociception accompanied by high titer, high opioid affinity serum antibodies similar to the immunopotentiating properties of traditional alum-based adjuvants. Moreover, nonhuman primates vaccinated with a heroin/fentanyl combination vaccine demonstrated potent antibody responses against opioids when formulated with both inulin and alum adjuvants. Finally, storing a freeze-dried opioid vaccine formulation maintained efficacy for up 1 year at room temperature. The results from our studies represent an advance toward a clinically feasible opioid vaccine.
The near insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing small molecule drugs continue to inadequately address OUD due to their engagement of the opioid receptor, which can leave the user to deal with side effects and financial hardships from their repeated use. An alternative therapeutic approach utilizes endogenously-generated antibodies through active vaccination to reduce the effect of opioids without modulating the opioid receptor. Here, we explore different adjuvants and storage conditions to improve opioid vaccine efficacy and shelf-life. Our results revealed that inulin-based formulations (Advax ™ ) containing a CpG oligodeoxynucleotide (ODN) acted as effective adjuvants when combined with a heroin conjugate: immunized mice showed excellent recovery from heroin-induced antinociception accompanied by high titer, high opioid affinity serum antibodies similar to the immunopotentiating properties of traditional alum-based adjuvants. Moreover, non-human primates vaccinated with a heroin/fentanyl combination vaccine demonstrated potent antibody responses against opioids when formulated with both inulin and alum adjuvants. Finally, storing a freeze-dried opioid vaccine formulation maintained efficacy for up 1 year at room temperature. The results from our studies represent an advance toward a clinically feasible opioid vaccine.
Author Zhou, Bin
Blake, Steven
Smith, Lauren C
Janda, Kim D
Bremer, Paul T
Petrovsky, Nikolai
Hwang, Candy S
AuthorAffiliation Vaxine Pty Ltd, 11 Walkley Avenue, Warradale 5046, South Australia, Australia
Flinders Medical Centre, Flinders University, GPO Box 2100, Adelaide 5001, South Australia, Australia
Cessation Therapeutics, LLC, 3031 Tisch Way, San Jose, California 95128, United States
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
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Issue 1
Keywords vaccine
heroin
fentanyl
carrier protein
immunopharmacotherapy
adjuvants
opioids
Language English
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Snippet The nearly insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters,...
The near insurmountable adversity that accompanies opioid use disorder (OUD) creates life-altering complications for opioid users. To worsen matters, existing...
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SubjectTerms Adjuvants, Immunologic - pharmacology
Adjuvants, Pharmaceutic - pharmacology
Analgesics, Opioid - immunology
Animals
Fentanyl - immunology
Heroin - immunology
Immunization - methods
Male
Mice
Mice, Inbred BALB C
Oligodeoxyribonucleotides - immunology
Opioid-Related Disorders - immunology
Vaccination - methods
Vaccines, Conjugate - immunology
Title Developing Translational Vaccines against Heroin and Fentanyl through Investigation of Adjuvants and Stability
URI https://www.ncbi.nlm.nih.gov/pubmed/33301675
https://pubmed.ncbi.nlm.nih.gov/PMC9946458
Volume 18
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