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Intranasal SARS-CoV-2 Omicron Variant Vaccines Elicit Humoral and Cellular Mucosal Immunity in Mice

36 Pages Posted: 11 Jul 2023

See all articles by Stefan Slamanig

Stefan Slamanig

Mount Sinai School of Medicine - Department of Microbiology

Irene Gonzalez-Dominguez

Mount Sinai School of Medicine - Department of Microbiology

Lauren Chang

National Institutes of Health - Vaccine Research Center

Nicholas Lemus

Mount Sinai School of Medicine - Department of Microbiology

Tsoi Ying Lai

Mount Sinai School of Medicine - Department of Microbiology

Jose L. Martinez

Mount Sinai School of Medicine - Department of Microbiology

Victoria Dolange

Mount Sinai School of Medicine - Department of Microbiology

Adam Abdeljawad

Mount Sinai School of Medicine - Department of Microbiology

Shreyas Kowdle

Mount Sinai School of Medicine - Department of Microbiology

Moataz Noureddine

Mount Sinai School of Medicine - Department of Microbiology

Gagandeep Singh

Mount Sinai School of Medicine - Department of Microbiology

Gagandeep Singh

Mount Sinai School of Medicine - Department of Microbiology

Benhur Lee

Mount Sinai School of Medicine - Department of Microbiology

Adolfo Garcia-Sastre

QBI Coronavirus Research Group (QCRG); Mount Sinai Health System - Global Health and Emerging Pathogens Institute; Mount Sinai Health System - Department of Medicine, Division of Infectious Diseases; Mount Sinai Health System - Tisch Cancer Institute; Mount Sinai Health System - Department of Pathology, Molecular and Cell-Based Medicine; Mount Sinai School of Medicine - Department of Microbiology

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Michael Schotsaert

Mount Sinai Health System - Department of Microbiology

Peter Palese

Mount Sinai School of Medicine - Department of Microbiology

Weina Sun

Mount Sinai School of Medicine - Department of Microbiology

More...

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 stabilized 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 mice. Furthermore, 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 characterized.

Findings: NDV-HXP-S variant vaccines elicited high mucosal IgA and serum IgG titers against respective VOC in mice following IN administration. 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 variant vaccines utilized 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) contract 75N93021C00014 (to P.P. and A.G.S.) and by the NIAID Collaborative Vaccine Innovation Centers contract 75N93019C00051 (to P.P.), by NIAID grant R01 AI145870 (to P.P.) and by institutional funding from the Icahn School of Medicine at Mount Sinai (to P.P.). SARS-CoV-2 work in the Schotsaert lab is funded by NIH/NIAID R01AI160706, NIH/NIAID R21AI176069 and NIH/NIDDK R01DK130425 (to M.S.).

Declaration of Interest: The Icahn School of Medicine at Mount Sinai has filed patent applications entitled “RECOMBINANT NEWCASTLE DISEASE VIRUS EXPRESSING SARS-COV-2 SPIKE PROTEIN AND USES THEREOF” which names P.P., A.G.S, F.K. and W.S. as inventors. Mount Sinai is seeking to commercialize this vaccine; therefore, the institution and its faculty inventors could benefit financially. The M.S. laboratory has received unrelated research funding in sponsored research agreements from 7Hills Pharma, ArgenX N.V., Moderna and Phio Pharmaceuticals, which has no competing interest with this work. FK has consulted for Merck, Seqirus, Curevac and Pfizer, and is currently consulting for Pfizer, Third Rock Ventures, GSK and Avimex. The FK laboratory is also collaborating with Pfizer on animal models of SARS CoV-2. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus and Pfizer. A.G.S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. Specifically, A.G.S., a member of the faculty of the Icahn School of Medicine at Mount Sinai (Mount Sinai) is an inventor of a novel COVID-19 vaccine currently being investigated in clinical trials. Mount Sinai is advancing the development of this vaccine and related technologies for potential commercial use. Mount Sinai has created CastleVax Inc., a Mount Sinai company, and has licensed the applicable IP to it. Mount Sinai will receive financial compensation from CastleVax Inc. pursuant to that license if vaccine development proceeds and as an owner of the company subject to the sale of its ownership interest in the future. Subject to Mount Sinai receiving such financial consideration, A.G.S. will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy 730All other authors declare no competing interests.

Ethical Approval: All the animal experiments were performed in accordance with protocols approved by the Icahn School of Medicine at Mount Sinai Institutional Animal Care and Use Committee (IACUC). All the animals were housed in a temperature/humidity-controlled facility with 12 h light/dark cycle.

Keywords: COVID-19, mucosal immune response, low cost vaccine platform, variant vaccine, NDV vector, mRNA vaccine, prime-pull vaccination

Suggested Citation

Slamanig, Stefan and Gonzalez-Dominguez, Irene and Chang, Lauren and Lemus, Nicholas and Lai, Tsoi Ying and Martinez, Jose L. and Dolange, Victoria and Abdeljawad, Adam and Kowdle, Shreyas and Noureddine, Moataz and Singh, Gagandeep and Singh, Gagandeep and Lee, Benhur and Garcia-Sastre, Adolfo and Krammer, Florian and Schotsaert, Michael and Palese, Peter and Sun, Weina, Intranasal SARS-CoV-2 Omicron Variant Vaccines Elicit Humoral and Cellular Mucosal Immunity in Mice. Available at SSRN: https://ssrn.com/abstract=4503317 or http://dx.doi.org/10.2139/ssrn.4503317

Stefan Slamanig

Mount Sinai School of Medicine - Department of Microbiology ( email )

Irene Gonzalez-Dominguez

Mount Sinai School of Medicine - Department of Microbiology ( email )

Lauren Chang

National Institutes of Health - Vaccine Research Center ( email )

Bethesda, MD 20892-9806
United States

Nicholas Lemus

Mount Sinai School of Medicine - Department of Microbiology ( email )

Tsoi Ying Lai

Mount Sinai School of Medicine - Department of Microbiology ( email )

Jose L. Martinez

Mount Sinai School of Medicine - Department of Microbiology ( email )

Victoria Dolange

Mount Sinai School of Medicine - Department of Microbiology ( email )

Adam Abdeljawad

Mount Sinai School of Medicine - Department of Microbiology ( email )

Shreyas Kowdle

Mount Sinai School of Medicine - Department of Microbiology ( email )

New York, NY
United States

Moataz Noureddine

Mount Sinai School of Medicine - Department of Microbiology ( email )

Gagandeep Singh

Mount Sinai School of Medicine - Department of Microbiology ( email )

Gagandeep Singh

Mount Sinai School of Medicine - Department of Microbiology ( email )

Benhur Lee

Mount Sinai School of Medicine - Department of Microbiology ( email )

Adolfo Garcia-Sastre

QBI Coronavirus Research Group (QCRG) ( email )

San Francisco, CA 94158
United States

Mount Sinai Health System - Global Health and Emerging Pathogens Institute ( email )

New York, NY
United States

Mount Sinai Health System - Department of Medicine, Division of Infectious Diseases ( email )

New York, NY
United States

Mount Sinai Health System - Tisch Cancer Institute ( email )

United States

Mount Sinai Health System - Department of Pathology, Molecular and Cell-Based Medicine ( email )

New York, NY
United States

Mount Sinai School of Medicine - Department of Microbiology ( email )

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Michael Schotsaert

Mount Sinai Health System - Department of Microbiology ( email )

United States

Peter Palese

Mount Sinai School of Medicine - Department of Microbiology ( email )

Weina Sun (Contact Author)

Mount Sinai School of Medicine - Department of Microbiology ( email )

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