# Safety/Tolerability/Immunogenicity of first-in-human Aβ DNA vaccine, AV-1959D Phase 1 trials in early-stage AD subjects: based on IND18953 cleared by FDA.

> **NIH AG R01** · INSTITUTE FOR MOLECULAR MEDICINE · 2026 · $2,115,510

## Abstract

Project Summary
Recent data from clinical trials with humanized or fully human mAbs targeting Aβ suggest that immunotherapy
could clear/reduce brain amyloid plaques and even slow cognitive decline in vaccinated subjects when initiated
as a preventive measure. However, passive immunotherapy with even the most effective anti-Aβ mAb is not
practical and cost-effective as a preventive measure in healthy subjects due to the need for frequent (monthly)
administrations of high concentrations (~800mg IV injections/each time) of this immunotherapeutic in a
substantial patient population. At the same time, high doses of mAb frequently (~30%) induce ARIA-E and ARIA-
H. In contrast, AD vaccine, similar to the vast majority of vaccines in general, could be very effective when used
as a preventive/early intervention measure. Today, only limited results are available from ACC001, CAD106,
and UB311 epitope vaccine clinical trials, but fortunately, comprehensive data on AN-1792 are published. These
data demonstrated that the AN-1792 vaccine has induced antibodies specific to N-terminus of amyloid in ~19%
immunized AD patients without causing ARIA-E and ARIA-H abnormalities. Importantly the follow-up analysis
revealed that even after 14 years post-vaccination, the vaccinated subjects were plaque-free, and there was a
significant inverse correlation between peripheral blood anti-Aβ antibody titers and the plaque counts. Despite
the reduction of Aβ pathology, vaccination did not improve cognitive functions likely due to tau pathology buildup.
These data support our long-standing proposal of starting anti-Aβ vaccination with AV-1959D as a prophylactic
measure in subjects at risk for AD to inhibit/reduce oligomerization of Aβ and delay downstream pathological
processes. However, based on an ethical imperative raised by the FDA during our pre-IND meeting, they
recommended us to test our Aβ vaccine AV-1959D in participants with early-stage AD patients prior to initiating
the preventive tri

## Key facts

- **NIH application ID:** 11300264
- **Project number:** 5R01AG074983-05
- **Recipient organization:** INSTITUTE FOR MOLECULAR MEDICINE
- **Principal Investigator:** Michael G Agadjanyan; LON S SCHNEIDER; David  Sultzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AG
- **Fiscal year:** 2026
- **Award amount:** $2,115,510
- **Award type:** 5
- **Project period:** 2022-02-15T00:00:00 → 2027-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11300264

## Citation

> US National Institutes of Health, RePORTER application 11300264, Safety/Tolerability/Immunogenicity of first-in-human Aβ DNA vaccine, AV-1959D Phase 1 trials in early-stage AD subjects: based on IND18953 cleared by FDA. (5R01AG074983-05). Retrieved via AI Analytics 2026-07-11 from https://api.ai-analytics.org/grant/nih/11300264. Licensed CC0.

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