Immunogenicity and efficacy of homologous and heterologous NDV and MVA SARS-CoV-2 vaccines in mice and hamsters
Effective vaccination strategies adaptable to emerging viruses like SARS-CoV-2 and capable of inducing robust protective immunity are needed. We evaluated the immunogenicity and protective efficacy of homologous and heterologous prime/boost regimens against SARS-CoV-2 in K18-hACE2 mice and Syrian hamsters using Newcastle disease virus (NDV-HXP-S, intranasal) and modified vaccinia virus Ankara (MVA-S(3P), intramuscular) vectors encoding a prefusion-stabilized SARS-CoV-2 spike (S) protein. All regimens protected against weight loss and markedly reduced viral replication and lung pathology. Vaccination induced serum anti-S and anti-receptor binding domain IgGs and neutralizing antibodies against ancestral virus and variants. In mice, mucosal anti-S IgA and IgG were detected after NDV-HXP-S immunization. Homologous MVA-S(3P)/MVA-S(3P) and heterologous NDV-HXP-S/MVA-S(3P) elicited higher polyfunctional systemic T-cell responses, while homologous NDV-HXP-S/NDV-HXP-S induced stronger pulmonary CD8<sup>+</sup> T cells. Hamsters vaccinated with NDV-HXP-S exhibited protection of the upper respiratory tract, with the NDV-HXP-S/MVA-S(3P) regimen showing a trend toward reduced direct contact transmission of SARS-CoV-2. These findings demonstrate the capacity of NDV and MVA vector platforms to induce robust systemic and mucosal antigen-specific humoral and T-cell responses against SARS-CoV-2, contributing to protection against both disease and transmission, and support further exploration of these vector platforms for vaccination against SARS-CoV-2 and potentially other pathogens.
Authors
- Weina Sun (ORCID: https://orcid.org/0000-0002-2435-5047)
- Nicholas Lemus (ORCID: https://orcid.org/0009-0006-9055-6513)
- Adolfo Garcı́a-Sastre (ORCID: https://orcid.org/0000-0002-6551-1827)
- Kaijun Jiang (ORCID: https://orcid.org/0000-0002-3607-2220)
- Mariano Estéban (ORCID: https://orcid.org/0000-0003-0846-2827)
- Stefan Slamanig (ORCID: https://orcid.org/0000-0003-3694-6597)
- Sara Flores (ORCID: https://orcid.org/0000-0002-4750-4244)
- Patricia Pérez (ORCID: https://orcid.org/0000-0001-8983-6784)
- Daniel Rodríguez-Martín (ORCID: https://orcid.org/0000-0002-6838-6355)
- Tsoi Ying Lai
- Juan García‐Arriaza (ORCID: https://orcid.org/0000-0002-5167-5724)
- Irene González‐Domínguez (ORCID: https://orcid.org/0000-0002-7920-5505)
- María A. Noriega
- Anastasija Čupić (ORCID: https://orcid.org/0000-0002-1291-1042)
- Adam Abdeljawad
- Pedro J. Sánchez‐Cordón (ORCID: https://orcid.org/0000-0002-7202-6475)
Institutions
- Consejo Superior de Investigaciones Científicas (ES)
- Instituto de Salud Carlos III (ES)
- Centro Nacional de Biotecnología (ES)
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (ES)
- Centro de Investigación Biomédica en Red (ES)
- Tisch Hospital (US)
- University of Amsterdam (NL)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1038/s41541-025-01299-3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Icahn School of Medicine at Mount Sinai
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
- Ministerio de Ciencia, Innovación y Universidades
- European Commission
- KU Leuven
- National Institutes of Health
- Agencia Estatal de Investigación
- National Institute of Allergy and Infectious Diseases
- Centro Nacional de Biotecnología