Publication date: Jun 30, 2026
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. 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. 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. 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. Supported by the Icahn School of Medicine Dean’s Philanthropic Fund, CastleVax Inc. , Mount Sinai CTSA (UL1TR004419), and philanthropic and federal grants. ClinicalTrials. govNCT05181709.
| Concepts | Keywords |
|---|---|
| 365days | COVID-19 vaccine |
| Cd4 | Intranasal vaccination |
| Severe | Mucosal immunity |
| Vaccinated | SARS-CoV-2 |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | Newcastle disease |
| disease | MESH | COVID-19 |