Key result
NDV-HXP-S proves safe and maintains or boosts serum IgG versus placebo across multiple delivery routes.
Why the study?
Intramuscular vaccines against SARS-CoV-2 protect against severe disease but provide limited mucosal protection.
Does live NDV-HXP-S administered intranasally, intramuscularly, or simultaneously improve immune responses and maintain safety in previously vaccinated healthy adults?
RCT (n=35)
No
Does live NDV-HXP-S administered intranasally, intramuscularly, or simultaneously improve immune responses and maintain safety in previously vaccinated healthy adults?
In a small Phase 1 trial, the live NDV-HXP-S vaccine was safe and elicited variable systemic and mucosal immune responses, supporting further clinical development.
NDV-HXP-S appears tolerable in small Phase 1 cohorts; leaves open whether mucosal boosting enhances protection versus standard IM regimens.
Background Newcastle disease virus hexapro spike (NDV-HXP-S) is a recombinant vaccine designed to elicit both systemic and mucosal immunity against SARS-CoV-2. Intramuscular vaccines protect against severe disease but provide limited mucosal protection. We conducted a Phase 1 trial of live NDV-HXP-S administered intranasally (IN), intramuscularly (IM), or simultaneously (IN+IM) in previously vaccinated adults. Methods Thirty-five healthy adults without prior COVID-19 were enrolled at a single site in New York City (Feb 2022–Apr 2024). Participants received low- or high-dose NDV-HXP-S via IN, IM, or IN+IM routes, or placebo. Safety was monitored for 365 days; immune responses in serum and saliva were measured through day 84. Findings All 35 participants completed follow-up. NDV-HXP-S was safe and well tolerated, with only grade 1–2 adverse events. Placebo recipients showed waning antibody titers, whereas NDV-HXP-S maintained or boosted serum IgG and neutralizing activity. Salivary sIgA rose modestly. Participants with low baseline CD4+ T-cell activity exhibited increases by day 28. The study was not powered for statistical significance. Interpretation Live NDV-HXP-S was safe and well tolerated in this small Phase 1 study. Exploratory immunogenicity analyses showed variable systemic and mucosal responses, supporting further evaluation of updated NDV-HXP-S formulations in larger controlled studies. Funding Supported by the Icahn School of Medicine Dean's Philanthropic Fund, CastleVax Inc., Mount Sinai CTSA (UL1TR004419), and philanthropic and federal grants. Trial registration ClinicalTrials.gov NCT05181709 .
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Liu et al. (2026) conducted an RCT in SARS-CoV-2 (n=35). NDV-HXP-S vs. Placebo was evaluated on Safety and immune responses. NDV-HXP-S administered via IN, IM, or IN+IM routes was safe with only grade 1-2 adverse events and maintained or boosted serum IgG compared to placebo.
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