Phase 1 trial of intranasal NDV-HXP-S in previously vaccinated adults
Year: 2026
Type: article
Abstract: 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.govNCT05181709.
Source: Vaccine
Authors: Sean T.H. Liu, Irene González-Domínguez, Amparo Martínez-Pérez, Cansu Cimen Bozkus, Oscar Bladh, Tarashon Broomes-Pennicott, Alina Jen, Elizabeth Egan, Edna Leiva-Ortiz, Ashley Abid, Katherina Aguilera, Mikael Åberg, Disha Bhavsar, Temima Yellin, Anass Abbad, Gagandeep Singh, Juan Manuel Carreño, Joshua Adams, Christina Quigley, Mansi Saxena, Marcia Meseck, Ilaria Ceglia, Charlotte Thålin, Daniela Weiskopf, Adolfo García-Sastre, Peter Palese, Weina Sun, Florian Krammer, Judith A. Aberg
Institutions: Icahn School of Medicine at Mount Sinai, La Jolla Institute for Immunology, University of California San Diego, Tisch Cancer Institute, Danderyds sjukhus, Karolinska Institutet, Uppsala University, Science for Life Laboratory, Cincinnati Children's Hospital Medical Center, Medical University of Vienna
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,620
OpenAlex ID: W7166553996