Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female miceResearch in context
Stefan Slamanig,
Irene González-Domínguez,
Lauren A. Chang,
Nicholas Lemus,
Tsoi Ying Lai,
Jose Luis Martínez,
Gagandeep Singh,
Victoria Dolange,
Adam Abdeljawad,
Shreyas Kowdle,
Moataz Noureddine,
Prajakta Warang,
Gagandeep Singh,
Benhur Lee,
Adolfo García-Sastre,
Florian Krammer,
Michael Schotsaert,
Peter Palese,
Weina Sun
Affiliations
Stefan Slamanig
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
Irene González-Domínguez
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Lauren A. Chang
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Nicholas Lemus
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Tsoi Ying Lai
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Jose Luis Martínez
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Gagandeep Singh
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Victoria Dolange
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Adam Abdeljawad
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Shreyas Kowdle
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Moataz Noureddine
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Prajakta Warang
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Gagandeep Singh
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA
Benhur Lee
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Adolfo García-Sastre
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Florian Krammer
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Michael Schotsaert
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Peter Palese
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Weina Sun
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding author.
Summary: Background: In order to prevent the emergence and spread of future variants of concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing vaccines capable of stopping transmission is crucial. The SARS-CoV-2 vaccine NDV-HXP-S can be administered live intranasally (IN) and thus induce protective immunity in the upper respiratory tract. The vaccine is based on Newcastle disease virus (NDV) expressing a stabilised SARS-CoV-2 spike protein. NDV-HXP-S can be produced as influenza virus vaccine at low cost in embryonated chicken eggs. Methods: The NDV-HXP-S vaccine was genetically engineered to match the Omicron variants of concern (VOC) BA.1 and BA.5 and tested as an IN two or three dose vaccination regimen in female mice. Furthermore, female mice intramuscularly (IM) vaccinated with mRNA-lipid nanoparticles (LNPs) were IN boosted with NDV-HXP-S. Systemic humoral immunity, memory T cell responses in the lungs and spleens as well as immunoglobulin A (IgA) responses in distinct mucosal tissues were characterised. Findings: NDV-HXP-S Omicron variant vaccines elicited high mucosal IgA and serum IgG titers against respective SARS-CoV-2 VOC in female mice following IN administration and protected against challenge from matched variants. Additionally, antigen-specific memory B cells and local T cell responses in the lungs were induced. Host immunity against the NDV vector did not interfere with boosting. Intramuscular vaccination with mRNA-LNPs was enhanced by IN NDV-HXP-S boosting resulting in improvement of serum neutralization titers and induction of mucosal immunity. Interpretation: We demonstrate that NDV-HXP-S Omicron variant vaccines utilised for primary immunizations or boosting efficiently elicit humoral and cellular immunity. The described induction of systemic and mucosal immunity has the potential to reduce infection and transmission. Funding: This work was partially funded by the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) and by the NIAID Collaborative Vaccine Innovation Centers and by institutional funding from the Icahn School of Medicine at Mount Sinai. See under Acknowledgements for details.
