Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection

Momtchilo Russo
* ,
Maria Cássia Mendes-Corrêa
,
Bruna Bezerra Lins
,
Victor Kersten
,
Paulo C. A. Pernambuco Filho
,
Toni Ricardo Martins
ORCID logo ,
Tania R. Tozetto-Mendoza
,
Lucy S Vilas Boas
,
Brisa M. Gomes
,
Livia Dati
,
Amaro N Duarte-Neto
ORCID logo ,
Gustavo R. Reigado
ORCID logo ,
Ana Beatriz Teixeira Frederico
ORCID logo ,
Danielle R. de A. De Brito e Cunha
ORCID logo ,
Anderson V. De Paula
,
Jose G. Da Silva
ORCID logo ,
Carlos M. Vasconcelos
ORCID logo ,
Felipe S. Chambergo
,
Viviane A. Nunes
,
Ana Paula Dinis Ano Bom
,
Leda R. Castilho
ORCID logo ,
Rodrigo T. Martins
,
Mario Hiroyuki Hirata
ORCID logo ,
Luciana Mirotti
Version 1 : Received: 8 October 2023 / Approved: 9 October 2023 / Online: 9 October 2023 (11:43:57 CEST)

A peer-reviewed article of this Preprint also exists.

Russo, M.; Mendes-Corrêa, M.C.; Lins, B.B.; Kersten, V.; Pernambuco Filho, P.C.A.; Martins, T.R.; Tozetto-Mendoza, T.R.; Vilas Boas, L.S.; Gomes, B.M.; Dati, L.M.M.; Duarte-Neto, A.N.; Reigado, G.R.; Frederico, A.B.T.; de Brito e Cunha, D.R.A.; de Paula, A.V.; da Silva, J.I.G.; Vasconcelos, C.F.M.; Chambergo, F.S.; Nunes, V.A.; Ano Bom, A.P.D.; Castilho, L.R.; Martins, R.A.P.; Hirata, M.H.; Mirotti, L. Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection. Vaccines 2023, 11, 1732. Russo, M.; Mendes-Corrêa, M.C.; Lins, B.B.; Kersten, V.; Pernambuco Filho, P.C.A.; Martins, T.R.; Tozetto-Mendoza, T.R.; Vilas Boas, L.S.; Gomes, B.M.; Dati, L.M.M.; Duarte-Neto, A.N.; Reigado, G.R.; Frederico, A.B.T.; de Brito e Cunha, D.R.A.; de Paula, A.V.; da Silva, J.I.G.; Vasconcelos, C.F.M.; Chambergo, F.S.; Nunes, V.A.; Ano Bom, A.P.D.; Castilho, L.R.; Martins, R.A.P.; Hirata, M.H.; Mirotti, L. Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection. Vaccines 2023, 11, 1732.

Abstract

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate to COVID-19 constituted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight lost and mortality indicators. However, when compared to the subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine that was more robust than homologous immunity.

Keywords

SARS-CoV-2; vaccine; hACE2 transgenic mice; intranasal route; spike protein; cationic liposome; CpG-ODNs; heterologous immunity

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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