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Novel Mechanisms of Protection from Substance Abuse Drugs

Award Number: R21DA065065
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Novel Mechanisms of Protection from Substance Abuse Drugs - SUMMARY The objective of this proposal is to determine the mechanisms that produce protective immunity for neurotropic chemicals such as fentanyl, cocaine, and nicotine. This proposal is in response to PAR-25-101 Cutting-Edge Basic Research Awards (CEBRA). Annual US overdose deaths have risen alarmingly to over 100,000 from fentanyl (FEN) which is often combined with cocaine. Additionally, annual US deaths related to nicotine addiction average 435,000. It has become evident that the development of alternative therapeutic strategies is of paramount importance. Generation of protective host immunity against addictive substances has demonstrated limited success using monoclonal antibodies or vaccines. However, we recently showed that FEN vaccination admixed with specific adjuvants and delivery routes markedly blocked FEN-induced analgesia and penetration into the brain. In addition, FEN-specific IgA correlated best with protection from FEN challenge. Additional research has recently identified meningeal plasma cells as key protective cells for the brain against infection. We believe that either IgA isotypes and/or a brain specific “antibody helmet” is the key to generating protective immunity against drugs involved in substance use disorders (SUD). Such immunity could be used to help prevent relapse and avert addiction related deaths. Here, we aim to perform basic research to define if specific antibody isotypes or locations of antibody secreting cells provide a protective phenotype from drugs involved in SUD. To achieve this, our proposal aims to conduct the following studies: (1) Test if targeted depletion of meningeal plasma cells will eliminate protective immunity against SUD in a mouse model. (2) Use two-photon cranial window imaging to determine in real time how meningeal plasma cells correlate to protection against SUD. (3) Determine if specific isotypes (e.g. IgA) or antibody locations (CSF, serum) are critical for protection against SUD. These studies have the potential to be paradigm shifting as to how best to activate host immunity to protect the brain from SUDs and toxic substances.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $229,500 )
2026	2026	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Drug Use and Addiction Research Programs	000	1	4/27/2026	NEW	$229,500
														Subtotal = $229,500

Grand Total All Awards = $229,500

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Novel Mechanisms of Protection from Substance Abuse Drugs

Award Number: R21DA065065

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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