Premium
IND‐enabling studies of vaccines to treat heroin and oxycodone use disorders
Author(s) -
Raleigh Michael,
King Samantha,
Saykao Amy,
Robinson Christine,
Baruffaldi Federico,
Gradinati Valeria,
Winston Scott,
LeSage Mark,
Pentel Paul,
Pravetoni Marco
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02440
Subject(s) - oxycodone , medicine , pharmacology , heroin , opioid , (+) naloxone , fentanyl , pharmacokinetics , morphine , methadone , in vivo , naltrexone , buprenorphine , anesthesia , drug , biology , receptor , microbiology and biotechnology
To treat opioid use disorder (OUD), a vaccine targeting oxycodone (OXY‐sKLH) is currently in a Phase I Clinical Trial and an analogous heroin vaccine (M‐sKLH) is being prepared for clinical testing. For both vaccines, key studies were performed to demonstrate the in vivo efficacy and selectivity against their respective target opioids in rats. Sprague Dawley rats were vaccinated with either OXY‐sKLH or M‐sKLH adsorbed to aluminum adjuvant and compared against controls consisting of either sKLH or aluminum alone. OXY‐sKLH protected against oxycodone‐induced, but not methadone‐induced, antinociception and respiratory depression, compared to controls, while naloxone's reversal effects remained intact. In addition, vaccination with OXY‐sKLH did not interfere with fentanyl distribution to serum and brain. M‐sKLH similarly protected against heroin‐induced effects while maintaining the effects of methadone and naloxone. Distribution of buprenorphine was also unaffected by vaccination with M‐sKLH. These in vivo data confirm the previously reported in vitro selectivity of OXY‐sKLH and M‐sKLH for their targeted opioids. To further support clinical implementation of OXY‐sKLH, follow‐up studies demonstrated that OXY‐sKLH elicited titers that remained high for at least 3‐5 months following a final vaccination, increased the half‐life of oxycodone 35‐fold, and reduced the reinforcing efficacy of oxycodone in an intravenous self‐administration model. No evidence of withdrawal was found during self‐administration. These data demonstrate that OXY‐sKLH produces a long‐lasting immune response and extensively alters oxycodone's pharmacokinetics and behavioral effects in rats, supporting its translation to human studies.