Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Virology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Vaccines and Antiviral Agents

Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype

Lisa Walz, Sarah-Katharina Kays, Gert Zimmer, Veronika von Messling
Stacey Schultz-Cherry, Editor
Lisa Walz
aVeterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah-Katharina Kays
aVeterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany
bGerman Centre for Infection Research (DZIF), TTU Emerging Infections, Langen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gert Zimmer
cInstitute of Virology and Immunology, Mittelhäusern, Switzerland
dDepartment of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gert Zimmer
Veronika von Messling
aVeterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany
bGerman Centre for Infection Research (DZIF), TTU Emerging Infections, Langen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Veronika von Messling
Stacey Schultz-Cherry
St. Jude Children's Research Hospital
Roles: Editor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JVI.01006-18
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • FIG 1
    • Open in new tab
    • Download powerpoint
    FIG 1

    Generation and characterization of influenza antigen-expressing VSV replicons. (A) Phylogenetic relationship of influenza A virus NA genes included in this study. Amino acid sequences were aligned using ClustalW and a phylogenetic tree constructed using the neighbor-joining method and 1,000 bootstrapped replications with observed amino acid differences as the distance on the aligned sequences using MEGA7. (B) Scheme of the genomes of the parental VSV and the recombinant VSV*ΔG replicons. VSV*ΔG lacks the gene encoding the VSV G protein and includes the eGFP gene in an additional transcription unit, depicted in gray. VSV*ΔG(X) encodes the respective heterologous influenza virus antigens, depicted in dark gray. (C) Vero E6 cells were surface biotin labeled with EZ-Link sulfo-NHS-biotin (Pierce) 12 h after infection with the respective VSV*ΔG replicons, followed by cell lysis and immunoprecipitation of 50 μg of cell extracts with homologous mouse antiserum. Proteins in the pellet fraction were separated on an SDS-PAGE gel, and surface biotin-labeled proteins were visualized using an avidin-HRP secondary antibody. (D) Protein bands from three independent replicates were quantified and normalized relative to NAPR8 for each blot and are shown as fold changes. Error bars represent the standard deviations of the means. Groups were compared using one-way ANOVA with a Tukey posttest, and statistical significance is indicated (*, P < 0.05; ns, not significant).

  • FIG 2
    • Open in new tab
    • Download powerpoint
    FIG 2

    Humoral and cellular immune responses in mice induced by the different VSV*ΔG replicons. (A) Schematic overview of the immunization strategy and blood and splenocyte sampling time points. Six- to eight-week-old naive C57BL/6 mice were immunized intramuscularly twice with 106 FFU of the VSV*ΔG replicons or with 2.5 μg of BPL-inactivated PR8 virus. (B and C) Kinetics of total antibody titers (B) and 50% neuraminidase-inhibiting (NI) antibody titers (C) against PR8 in animals immunized with matched antigens. Symbols represent the means for each group (n = 6), and error bars indicate the standard deviations of the means. (D and E) Total antibody titers (D) and NI titers (E) against all PR8, USSR, and H5N1 viruses. Bars represent the means for each group (n = 6), and error bars indicate the standard deviations of the means. Log2-transformed groups were compared to the NAPR8 group using one-way ANOVA with a Tukey posttest. (F) IFN-γ ELISpot analysis results after restimulation with purified PR8 virus. H1N1 PR8-infected mice were used as positive controls, and noninfected mice were used as negative controls. Symbols indicate spot-forming units (SFU) for individual animals, and black bars represent the respective means. Groups were compared using one-way ANOVA with a Tukey posttest, and statistical significance is indicated (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001).

  • FIG 3
    • Open in new tab
    • Download powerpoint
    FIG 3

    Protective efficacy of the different vaccine candidates. Mice were vaccinated once or twice in 4-week intervals and then challenged with 1 × 104 TCID50 of H1N1 PR8 4 weeks later. Upon challenge, animals were monitored daily for clinical signs and body weight and euthanized as soon as the weight loss reached 25%. (A to D) Percent weight changes after challenge following one (A) or two (B) immunizations and the respective percent survivals (C and D) (n = 6; N1 H5N1, n = 5). (E and F) Correlation between mean NI titer and percent survival 4 weeks after the first (E) or the second (F) immunization.

  • FIG 4
    • Open in new tab
    • Download powerpoint
    FIG 4

    Efficacy of passive serum transfer. (A) Schematic overview of the experimental design. Mice were vaccinated on days 0 and 28 with the respective VSV*ΔG replicons, and serum was isolated 7 days after the boost immunization. Sera were subsequently transferred into naive mice. Blood samples were taken 24 h later, and animals were challenged with 1 × 104 TCID50 of H1N1 PR8. (B) Total antibody responses against PR8 and NI titers of donor mice. Bars represent the means for three repeated measurements of pooled serum, and error bars indicate the standard deviations of the means. Log2-transformed groups were compared to the NAPR8 group using one-way ANOVA with a Tukey posttest. Statistical significance is indicated (*, P < 0.05; ****, P < 0.0001). (C and D) Percent weight change (C) and percent survival (D) in recipient mice. Upon challenge, body weight was monitored as a measure of morbidity. Animals were euthanized as soon as the weight loss reached 25%.

  • FIG 5
    • Open in new tab
    • Download powerpoint
    FIG 5

    Humoral immune responses in ferrets induced by the different VSV*ΔG replicons and viral load after infection. (A) Schematic overview of the immunization-and-infection strategy and blood sampling time points. Naive ferrets were immunized twice with 108 FFU VSV*ΔG replicons intramuscularly. All animals were challenged intranasally with 105 TCID50 A/Mexico/InDRE4487/2009 and sacrificed for virus titration on day 3 after infection. (B and C) Kinetics of total antibody titers (B) and NI titers (C) against pdmH1N1 in animals immunized with matched or mismatched antigens. Log2-transformed groups were compared using two-way ANOVA with a Tukey posttest. (D and E) Temperature changes (E) and clinical scores (F) measured over 3 days after infection. Symbols represent the means for each group (n = 4; postinfection N1 H5N1, n = 2), and error bars indicate the standard deviations of the means. (F and G) Virus titers in the nasal turbinates (F) and lungs (G) in terms of TCID50 per gram on MDCK cells. Symbols indicate data for individual animals, and black bars represent the respective means.

  • FIG 6
    • Open in new tab
    • Download powerpoint
    FIG 6

    Linear comparison of the NA proteins. The cytoplasmic domain, transmembrane region (TM), stalk region, and head domain are depicted in dark, medium and light gray, and white, respectively. Putative glycosylation sites are shown above, active sites are in red, and previously identified critical residues for inhibiting antibody binding are indicated by gray arrowheads and the respective amino acid numbering.

PreviousNext
Back to top
Download PDF
Citation Tools
Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype
Lisa Walz, Sarah-Katharina Kays, Gert Zimmer, Veronika von Messling
Journal of Virology Aug 2018, 92 (17) e01006-18; DOI: 10.1128/JVI.01006-18

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Virology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype
(Your Name) has forwarded a page to you from Journal of Virology
(Your Name) thought you would be interested in this article in Journal of Virology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Neuraminidase-Inhibiting Antibody Titers Correlate with Protection from Heterologous Influenza Virus Strains of the Same Neuraminidase Subtype
Lisa Walz, Sarah-Katharina Kays, Gert Zimmer, Veronika von Messling
Journal of Virology Aug 2018, 92 (17) e01006-18; DOI: 10.1128/JVI.01006-18
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • RESULTS
    • DISCUSSION
    • MATERIALS AND METHODS
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

correlates of protection
functional antibodies
influenza A virus
neuraminidase protein
VSV replicon vaccine platform

Related Articles

Cited By...

About

  • About JVI
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #Jvirology

@ASMicrobiology

       

 

JVI in collaboration with

American Society for Virology

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0022-538X; Online ISSN: 1098-5514