System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ppublish 16 citations

PubMed: 38848648 DOI: 10.1016/j.ebiom.2024.105185

Intranasal SARS-CoV-2 Omicron variant vaccines elicit humoral and cellular mucosal immunity in female mice.

EBioMedicine 105:105185

Authors: 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

  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands.
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 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.
  • 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 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 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.
  • 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.
  • 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.
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Abstract

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 NIAIDCenters 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.

MeSH

Cells, Sars-Cov-2, Lung, Serum, Vaccines, Biomedical Research, Vaccination, Immunoglobulin A, Immunity, Mucosal, Viruses, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus, Memory, Lipid Nanoparticles

Cited by