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Protection against SARS-CoV-2 transmission by a parenteral prime—Intranasal boost vaccine strategy

Dennis ChristensenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkCharlotta PolacekVirus Research & Development Laboratory, Department of Virology and Microbiological Special diagnostics, Statens Serum Institut, Copenhagen, DenmarkDaniel J. ShewardDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenLeo HankeDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenAinhoa Moliner MorroDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenGerald M. McInerneyDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenBen MurrellDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenKatrine Top HartmannDepartment of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen DenmarkHenrik Elvang JensenDepartment of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen DenmarkGregers JungersenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkKristin E. Engelhart IlligenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkLouise Krag IslingCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkRune Fledelius JensenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkJulia Sid HansenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkIda RosenkrandsCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkCarlota Fernandez-AntunezCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkSantseharay RamírezCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkFrank FollmannCenter for Vaccine Research, Statens Serum Institut, Copenhagen, DenmarkJens BukhCopenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkGabriel Kristian PedersenCenter for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark. Electronic address: [email protected]
2022en
ABI

Аннотация

BACKGROUND: Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission. METHODS: We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission. FINDINGS: Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission. INTERPRETATION: This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies. FUNDING: This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.

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