Immunogenicity and pre-clinical efficacy of an OMV-based SARS-CoV-2 vaccine

Grandi, Alberto; Tomasi, Michele; Accordini, Silvia; Bertelli, Cinzia; Vanzo, Teresa; Gagliardi, Assunta; Caproni, Elena; Tamburini, Silvia; Fantappiè, Laura; Lascio, Gabriele Di; Bisoffi, Zeno; Piubelli, Chiara; Valenti, Maria Teresa; Carbonare, Luca Dalle; Zipeto, Donato; Ravà, Micol; Fumagalli, Valeria; Lucia, Pietro Di; Marotta, Davide; Sala, Eleonora; Iannacone, Matteo; Cherepanov, Peter; Bolognesi, M.; Pizzato, Massimo; Grandi, Guido

doi:10.1101/2021.07.12.452027

Cited by 3 publications

(2 citation statements)

References 20 publications

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“…Intranasal immunization of mice with Bordetella pertussis OMVs induced mucosal IgA and Th17-mediated responses which prevented colonization of the nasal cavity and the lungs ( 40 ). OMVs derived from Salmonella typhimurium and Escherichia coli have recently also been used to present respectively the spike RBD or peptides derived from it, and in both cases immunization provided a protective response in animal models ( 56 , 57 ). In our OMV-mC-Spike vaccine, the full-length spike protein is included.…”

Section: Discussionmentioning

confidence: 99%

An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection

et al. 2021

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The development of more effective, accessible, and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector, and whole inactivated virus vaccines is essential to curtailing the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six-proline-stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to outer membrane vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells, and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum-neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination, hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs 7 days after challenge in OMV-mC-Spike-vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing.

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Section: Discussionmentioning

confidence: 99%

An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection

et al. 2021

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“…Intranasal immunization of mice with Bordetella pertussis OMVs induced mucosal IgA and Th17-mediated responses which prevented colonization of the nasal cavity and the lungs 53 . OMVs derived from Salmonella typhimurium and Escherichia coli have recently also been used to present respectively the Spike RBD or peptides derived from it, and in both cases intranasal immunization provided a protective response in animal models 54,55 . In our OMV-based COVID-19 vaccine the full length spike protein is included.…”

Section: And Meningococcalmentioning

confidence: 99%

An intranasal OMV-based vaccine induces high mucosal and systemic protecting immunity against a SARS-CoV-2 infection

Ley

Zariri

Riet

et al. 2021

Preprint

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The development of more effective, accessible and easy to administer COVID-19 vaccines next to the currently marketed mRNA, viral vector and whole inactivated vaccines, is essential to curtain the SARS-CoV-2 pandemic. A major concern is reduced vaccine-induced immune protection to emerging variants, and therefore booster vaccinations to broaden and strengthen the immune response might be required. Currently, all registered COVID-19 vaccines and the majority of COVID-19 vaccines in development are intramuscularly administered, targeting the induction of systemic immunity. Intranasal vaccines have the capacity to induce local mucosal immunity as well, thereby targeting the primary route of viral entry of SARS-CoV-2 with the potential of blocking transmission. Furthermore, intranasal vaccines offer greater practicality in terms of cost and ease of administration. Currently, only eight out of 112 vaccines in clinical development are administered intranasally. We developed an intranasal COVID-19 subunit vaccine, based on a recombinant, six proline stabilized, D614G spike protein (mC-Spike) of SARS-CoV-2 linked via the LPS-binding peptide sequence mCramp (mC) to Outer Membrane Vesicles (OMVs) from Neisseria meningitidis. The spike protein was produced in CHO cells and after linking to the OMVs, the OMV-mC-Spike vaccine was administered to mice and Syrian hamsters via intranasal or intramuscular prime-boost vaccinations. In all animals that received OMV-mC-Spike, serum neutralizing antibodies were induced upon vaccination. Importantly, high levels of spike-binding immunoglobulin G (IgG) and A (IgA) antibodies in the nose and lungs were only detected in intranasally vaccinated animals, whereas intramuscular vaccination only induced an IgG response in the serum. Two weeks after their second vaccination hamsters challenged with SARS-CoV-2 were protected from weight loss and viral replication in the lungs compared to the control groups vaccinated with OMV or spike alone. Histopathology showed no lesions in lungs seven days after challenge in OMV-mC-Spike vaccinated hamsters, whereas the control groups did show pathological lesions in the lung. The OMV-mC-Spike candidate vaccine data are very promising and support further development of this novel non-replicating, needle-free, subunit vaccine concept for clinical testing.

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