Looking forward to leading one of only two nationally awarded ‘Anti-Opioid Vaccine Development Programs’, along with @levy_o, and working with our fantastic @PrecVaccines team and collaborators from several institutions! Here is the official news: discoveries.childrenshospital.org/covid-19-opioi…
A brief thread to give an overview of our team, some background science on our anti-opioid vaccine strategy and put into perspective why I choose to work on this problem personally...
First, as outlined on our @PrecVaccines account, the goal of the award is to develop an adjuvanted #vaccine for treatment of #opioid use disorder, and bring it to a #Phase1 #ClinicalTrial right here @BostonChildrens:
https://twitter.com/PrecVaccines/status/1317112155808821248
Fentanyl is a synthetic, highly potent opioid that is often added to other drugs like heroin, cocaine, and sometimes even marijuana: drugabuse.gov/drug-topics/tr…
The number of drug overdose deaths involving fentanyl was stable in 2011 (~1000), 2012 (~1,500), began to increase in 2013, rising to ~20,00 deaths in 2016 (PMID 31112123).
In both 2017 and 2018, fentanyl accounted for nearly half of the ~70,000 fatal drug overdoses in the U.S. As outlined by Jalal et al. (PMID 30237320), the overall mortality rate for unintentional drug poisonings in the United States grew exponentially from 1979 through 2016: 
Opioid-related deaths are on the rise during the COVID-19 pandemic, with 2020 possibly being worse than prior years: nytimes.com/interactive/20…
Conversely, a recent @NIH funded study found that people with substance use disorders (SUDs) are more susceptible to COVID-19 and its complications, an effect that was strongest for opioid use disorder (OUD): nih.gov/news-events/ne…
Our project originally started in early 2019, funded by a @NIH supplement to our ongoing efforts to make vaccines more efficient in distinct populations: discoveries.childrenshospital.org/opioid-vaccine/
The proposed vaccine is intended for those with OUD and might be exposed to fentanyl (directly or through contamination), that will stimulate anti-fentanyl antibodies, blocking it from reaching the brain and suppressing respiration. Banks et al., 2017 (PMID 30343725) reviews:
A little about is our incredible team: Sharon Levy, Director of the Adolescent Substance Use & Addiction Program (ASAP) at @BostonChildrens will lead our recruitment and provide expert leadership on translation into a clinical trial: childrenshospital.org/centers-and-se…
@elissa_weitzman of the Weitzman Lab will lead out work on investigating the attitudes/beliefs of at-risk youth and other stakeholders toward an anti-fentanyl vaccine:
https://twitter.com/PrecVaccines/status/1319652065849716736?s=20
Our @PrecVaccines Associate Director, Al Ozonoff; faculty Simon van Haren; postdoctoral scientist @sdh33ru; Hanno Steen, Department of Pathology; Cindy Williams, and Andrew Place, both of the Institutional Centers for Clinical and Translational Research will manage our BCH teams.
Our national collaborators include Jay Evans and the talented team at Inimmune (Missoula, MT); Therese A. Kosten, Tom Kosten, Colin Haile and Greg Cuny, University of Houston (Houston, TX); and Christopher Chen of Texas Biomedical Research Institute.
For those new to adjuvant science, adjuvants enhance vaccine immunogenicity (i.e., the ability of a particular substance, such as an antigen, to provoke an immune response in vivo). We summarize this in our recent review ‘Toward Precision Adjuvants’: pubmed.ncbi.nlm.nih.gov/31904601/
Here we outline how adjuvants may have many benefits; including vaccine dose/antigen-sparing, broadening immune responses to variable antigens, and enhancing immunogenicity in vulnerable populations with distinct immunity (thanks @biorender):
However, Alum is still the only adjuvant used in licensed adjuvanted pediatric vaccines and few adjuvants are commonly employed in a precision vaccines fashion: frontiersin.org/articles/10.33…
As such, the right adjuvant may be key to boosting antibodies to the fentanyl-hapten antigens, blocking it from reaching the brain where respiration is controlled:
https://twitter.com/PrecVaccines/status/1319013076675407872?s=20
Our development plan for precision vaccines includes sequential approaches including system biology; use of human in vitro systems for hypothesis testing and targeted adjuvant discovery employing population-specific biosamples, appropriate animal models and clinical trials:
We will also employ medicinal chemistry and formulation approaches, which, as we have discussed recently, are increasing important to limit adjuvant-related systemic reactogenicity: nature.com/articles/s4139…
Lastly, why take on this project…
I grew up in Ireland in the 1980‘s and early 1990’s. During this time, Ireland was experiencing one of the first opioid epidemics to hit Europe.
As outlined by Kelleher et al., there was a marked increase in the number of opioid-related deaths during the mid and late 1990s: academic.oup.com/eurpub/article…
As such, watching the rise in opioid-related deaths in the past decade, especially in my adopted home Stateside, was very similar to those early experiences from back home in Ireland.
This time however, I hope I can use my experience and skills in immunology and vaccinology to directly work on a potential, if only partial, solution to this important modern problem in our societies…
Thanks for taking the time to learn about this exciting new project. Follow @PrecVaccines for regular updates.
PS. We appreciate the ongoing and kind funding support from @NIH @healinitiative @NIAIDNews @NIDAnews @BostonChildrens @ChildrensTIDO @BCH_Innovation @BCHPedsID
PPS. This is a very ambitious project with a forward leaning timeline, so feel free to support our efforts via our @PrecVaccines donation page (or contact me directly): secure.childrenshospital.org/site/Donation2…
PPPS. I will be posting new opportunities for postdoctoral positions, research assistant positions, project manager positions in the weeks ahead. Feel free to DM me or email me at david.dowling@childrens.harvard.edu for me info…
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