# Manufacturing of Drug Product, Dual Aβ/tau Vaccine for Clinical Trials

> **NIH NIH U01** · INSTITUTE FOR MOLECULAR MEDICINE · 2023 · $2,270,000

## Abstract

Project Summary
Immunotherapy is still considered a promising therapeutic strategy for AD prevention. Data from
various immunotherapeutic studies support our long-standing tenet that immunogenic AD
vaccines could at least delay disease progression when they target both Aβ and Tau pathological
molecules at an early stage of the disease or even in healthy people at AD risk. Recently FDA
announced emergency accelerated approval of mAb Aducanumab for treatment of early AD.
However, it is impractical to use very expensive mAbs as a preventive treatment for healthy
subjects due to the need for frequent (monthly) administration of high concentrations (700-800mg
per IV injection) of this immunotherapeutic. In contrast, almost all effective vaccines are effective
when they are used as a preventive treatment. Accordingly, the major goal of the IMM-NIA
cooperative U01 AG-60965 program is to manufacture single vaccines targeting tau or Aβ, and a
dual vaccine, targeting both pathological molecules together. Based on this goal within the scope
of the current program, we worked with Gates Biomanufacturing Facility (GBF) to manufacture
two components of the dual vaccine, AV-1980R and AV-1959R recombinant proteins (drug
substances), in a GMP format for first-human Phase I clinical trials. GBF developed two drug
substances, AV-1980R and AV-1959R, that were tested in pre-clinical IND-enabling
safety/toxicology studies. While GMP manufacturing of the first component of the dual vaccine,
AV-1980R, is initiated and will be completed in August 2022, unexpectedly, technical difficulties
arose with the production of the second component, AV-1959R. AV-1959R appeared to be a more
aggregation-prone protein than AV-1980R, which led to a different formulation and a substantial
decrease in AV-1959R production yield. While these difficulties are not significant for single
vaccines, AV-1959R or AV-1980R (IND preparation is ongoing), manufacturing/formulation
optimization is required for the dual vaccine prior to preparation and submission of IND. GBF team
has identified a technical path forward to protein yield increase and formulation based on their
experience and analytical tools such as dynamic light scattering, SDS-PAGE, and reverse-phase
HPLC. Therefore, this project aims to develop a formulation for AV-1959R, which will increase
the production yield of AV-1959R, support short and long-term stability, and manufacture a final
cGMP grade dual vaccine (drug product). The requested funds will cover the cost of process
development/formulation optimization of AV-1959R, manufacturing of cGMP AV-1959R drug
substance, formulation of dual vaccine, filling/lyophilization, packaging, and release tests, stability
of drug product dual vaccine.

## Key facts

- **NIH application ID:** 10667237
- **Project number:** 3U01AG060965-04S2
- **Recipient organization:** INSTITUTE FOR MOLECULAR MEDICINE
- **Principal Investigator:** Michael G Agadjanyan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $2,270,000
- **Award type:** 3
- **Project period:** 2019-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667237

## Citation

> US National Institutes of Health, RePORTER application 10667237, Manufacturing of Drug Product, Dual Aβ/tau Vaccine for Clinical Trials (3U01AG060965-04S2). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10667237. Licensed CC0.

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