bf223fb8a1b4639f235f9844cbe2d9e0 pmc_9692796.pdf 89d96d68a1ae3a3a73fe43b52b658063d00804b6 pmc_9692796.pdf e98fb01d3be48a7169cc9b62e3e291dd8763a108707cb884fec7cb60e8d9c21d pmc_9692796.pdf Title: Heterologous Systemic Prime–Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters Subject: Background: Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are administered systemically and typically result in poor immunogenicity at the mucosa. As a result, vaccination is unable to reduce viral shedding and transmission, ultimately failing to prevent infection. One possible solution is that of boosting a systemic vaccine via the nasal route resulting in mucosal immunity. Here, we have evaluated the potential of bacterial spores as an intranasal boost. Method: Spores engineered to express SARS-CoV-2 antigens were administered as an intranasal boost following a prime with either recombinant Spike protein or the Oxford AZD1222 vaccine. Results: In mice, intranasal boosting following a prime of either Spike or vaccine produced antigen-specific sIgA at the mucosa together with the increased production of Th1 and Th2 cytokines. In a hamster model of infection, the clinical and virological outcomes resulting from a SARS-CoV-2 challenge were ameliorated. Wuhan-specific sIgA were shown to cross-react with Omicron antigens, suggesting that this strategy might offer protection against SARS-CoV-2 variants of concern. Conclusions: Despite being a genetically modified organism, the spore vaccine platform is attractive since it offers biological containment, the rapid and cost-efficient production of vaccines together with heat stability. As such, employed in a heterologous systemic prime–mucosal boost regimen, spore vaccines might have utility for current and future emerging diseases. Keywords: COVID-19; SARS-CoV-2; nasal vaccine; prime boost Author: Paidamoyo M. Katsande, Leira Fernández-Bastit, William T. Ferreira, Júlia Vergara-Alert, Mateusz Hess, Katie Lloyd-Jones, Huynh A. Hong, Joaquim Segales and Simon M. Cutting Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Nov 10 12:33:01 2022 CET ModDate: Thu Nov 10 12:39:38 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1491403 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KPGTVT+VnURWPalladioL Type 1 Custom yes yes no 10 0 PKJJQN+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 RKDYVF+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 VEJFET+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 FYYAHQ+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 VIWIOF+CMSY10 Type 1 Builtin yes yes no 65 0 ZXDKIP+EURM10 Type 1 Builtin yes yes no 69 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 76 0 PCKLCA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 93 0 PCKLCB+PalatinoLinotype CID TrueType Identity-H yes 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PCKLCD+PalatinoLinotype,Italic CID TrueType Identity-H yes yes yes 192 0 PCKLCE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 198 0 PCKLCA+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 212 0 PCKLCC+PalatinoLinotype TrueType WinAnsi yes yes no 215 0 PCKLCE+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 218 0 AWDAAW+VnURWPalladioL-Italic Type 1 Custom yes yes no 228 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-12-08 02:27:57 CET RepresentationInformation: pmc_9692796.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-12-01 02:19:17 CET Size: 1491403 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 401 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: General Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Construction of B. subtilis Spores Expressing SARS-CoV-2 Antigens Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Immunogens Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Prime Boost Vaccination Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Determination of Mucosal and Systemic Antibody Titers by Indirect ELISA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Cytokine Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Hamster Challenge Study Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Children: Item: Title: Construction of B. subtilis Spores Displaying SARS-CoV-2 Domains Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Intranasal Boosting with a Spore Vaccine following a Systemic Prime Evokes Mucosal Immune Responses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Boosting with Spores Evokes Cross-Reactive Antibodies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Intranasal Boosting with a Spore Vaccine Results in a Mixed T Cell Cytokine Profile Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Intranasal Boosting with Spores Is Protective in the Hamster SARS-CoV-2 Model of Infection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Info: Title: Heterologous Systemic Prime Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters Author: Paidamoyo M. Katsande, Leira Fernández-Bastit, William T. Ferreira, Júlia Vergara-Alert, Mateusz Hess, Katie Lloyd-Jones, Huynh A. Hong, Joaquim Segales and Simon M. Cutting Subject: Background: Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are administered systemically and typically result in poor immunogenicity at the mucosa. As a result, vaccination is unable to reduce viral shedding and transmission, ultimately failing to prevent infection. One possible solution is that of boosting a systemic vaccine via the nasal route resulting in mucosal immunity. Here, we have evaluated the potential of bacterial spores as an intranasal boost. Method: Spores engineered to express SARS-CoV-2 antigens were administered as an intranasal boost following a prime with either recombinant Spike protein or the Oxford AZD1222 vaccine. Results: In mice, intranasal boosting following a prime of either Spike or vaccine produced antigen-specific sIgA at the mucosa together with the increased production of Th1 and Th2 cytokines. In a hamster model of infection, the clinical and virological outcomes resulting from a SARS-CoV-2 challenge were ameliorated. Wuhan-specific sIgA were shown to cross-react with Omicron antigens, suggesting that this strategy might offer protection against SARS-CoV-2 variants of concern. Conclusions: Despite being a genetically modified organism, the spore vaccine platform is attractive since it offers biological containment, the rapid and cost-efficient production of vaccines together with heat stability. As such, employed in a heterologous systemic prime mucosal boost regimen, spore vaccines might have utility for current and future emerging diseases. 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