Amyloid Vaccine AV-1959R Generates Antibodies in All Phase 1 Recipients

AV-1959R, an investigational amyloid-beta (Aβ) vaccine developed by Nuravax and the Institute for Molecular Medicine (IMM), was shown to induce anti-Aβ antibody responses in every vaccinated participant in a randomized phase 1 trial, according to newly published results in Molecular Neurodegeneration. Although not designed to evaluate to evaluate clinical efficacy, the study met its safety and immunogenicity objectives.¹

After a pair of priming immunizations given 1 month apart, all 12 AV-1959R recipients developed anti-Aβ antibodies. Notably, geometric mean titers (GMTs) reached 60,240 in the 100 µg cohort and 69,530 in the 300 µg cohort. None of the 4 placebo recipients showed a measurable response, and their anti-Aβ42 antibody levels stayed at baseline, with a GMT of 156. Based on those figures, vaccinated GMTs were roughly 386-fold and 446-fold higher than placebo. The release did not report P values or confidence intervals for the comparison.

“Amyloid-beta is a self-protein, which makes it difficult to generate a strong, targeted immune response against pathological forms of the protein,” said Michael Agadjanyan, PhD, head of Molecular Immunology at IMM and founder of Nuravax, in a statement.¹ “The Phase 1 results provide clinical evidence that MultiTEP-based AV-1959R can overcome immune tolerance and induce antibodies that preferentially recognize aggregated Aβ.”

In exploratory analyses, vaccine-induced antibodies bound most strongly to aggregated Aβ species, including protofibrils and fibrils, bound oligomers more weakly, and showed little to no binding to monomeric Aβ. Serum from vaccinated participants also bound amyloid plaques in cortical tissue from people with Alzheimer disease (AD) but not in non-AD control tissue.

Antibody-kinetics modeling projected that titers could remain approximately 5-fold above baseline for about 1 year after priming, a result the companies said supports testing an annual booster in future studies. Investigators noted that durability and clinical relevance still need to be confirmed prospectively.¹

According to the news release, the trial met its safety objectives, but the announcement did not report adverse event (AE) counts, serious AEs, or amyloid-related imaging abnormality (ARIA) findings by arm.¹ The registered protocol lists the number of participants with treatment-emergent or serious AEs as the primary end point.

“This 16-participant Phase 1 study provides an initial assessment of safety and immunogenicity but cannot establish the safety or efficacy of the vaccine,” Lon S. Schneider, MD, professor of psychiatry, neurology, and gerontology at the Keck School of Medicine of USC and a coauthor of the publication, said in a statement.^{1 “}The planned Phase 2 study is designed to evaluate these questions in participants with biomarker-confirmed amyloid pathology.”

Nuravax and IMM plan a phase 2 preventive trial in cognitively unimpaired individuals with biomarker-confirmed amyloid pathology across both low and high amyloid burden. The study is expected to expand safety monitoring to include ARIA with hemosiderin deposition (ARIA-H) and ARIA with edema or effusion (ARIA-E), and to assess surrogate efficacy through amyloid- and tau-related brain and blood biomarkers.

AV-1959R is built on the MultiTEP platform, which pairs self-antigen B-cell epitopes with foreign T-helper epitopes to provoke antibody responses against proteins the immune system would otherwise tolerate.The drug product was supplied by IMM under National Institutes of Health cooperative agreement U01 AG060965. AV-1959R is not approved for any use.¹

REFERENCE
1. Nuravax and Institute for Molecular Medicine announce publication of phase 1 results for AV-1959R amyloid-beta vaccine. News release. Nuravax, Inc. Published October 13, 2026. Accessed October 19, 2026. https://www.prnewswire.com/news-releases/nuravax-and-institute-for-molecular-medicine-announce-publication-of-phase-1-results-for-av-1959r-amyloid-beta-vaccine-302905613.html