Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

Jan Felix Drexler, Gilda Grard, Alexander N. Lukashev, Liubov I. Kozlovskaya, Sindy Böttcher, Gökhan Uslu, Johan Reimerink, Anatoly P. Gmyl, Raphaël Taty-Taty, Sonia Etenna Lekana-Douki, Dieudonné Nkoghe, Anna M. Eis-Hübinger, Sabine Diedrich, Marion Koopmans, Eric M. Leroy, and Christian Drosten
  1. aInstitute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany;
  2. bCentre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
  3. cChumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia;
  4. dRobert Koch Institute, National Reference Laboratory for Poliomyelitis and Enteroviruses, 13302 Berlin, Germany;
  5. eNetherlands Center for Infectious Disease Control, 3720, Bilthoven, The Netherlands;
  6. fLomonosov Moscow State University, Moscow 119991, Russia;
  7. gMinistry of Health, Pointe Noire, Republic of Congo; and
  8. hInstitut de Recherche pour le Développement, Unité Mixte de Recherche 224 (Maladies Infectieuses et Vecteurs: Écologie, Génétique, Évolution et Contrôle), Institut de Recherche pour le Développement/Centre National de la Recherche Scientifique/Unité Mixte 1, 34032 Montpellier, France

See allHide authors and affiliations

PNAS September 2, 2014 111 (35) 12889-12894; first published August 18, 2014; https://doi.org/10.1073/pnas.1323502111
Jan Felix Drexler
aInstitute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gilda Grard
bCentre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander N. Lukashev
cChumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liubov I. Kozlovskaya
cChumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sindy Böttcher
dRobert Koch Institute, National Reference Laboratory for Poliomyelitis and Enteroviruses, 13302 Berlin, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gökhan Uslu
eNetherlands Center for Infectious Disease Control, 3720, Bilthoven, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Johan Reimerink
eNetherlands Center for Infectious Disease Control, 3720, Bilthoven, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anatoly P. Gmyl
cChumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782, Russia;
fLomonosov Moscow State University, Moscow 119991, Russia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raphaël Taty-Taty
gMinistry of Health, Pointe Noire, Republic of Congo; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonia Etenna Lekana-Douki
bCentre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dieudonné Nkoghe
bCentre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna M. Eis-Hübinger
aInstitute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sabine Diedrich
dRobert Koch Institute, National Reference Laboratory for Poliomyelitis and Enteroviruses, 13302 Berlin, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marion Koopmans
eNetherlands Center for Infectious Disease Control, 3720, Bilthoven, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric M. Leroy
bCentre International de Recherches Médicales de Franceville, BP 769 Franceville, Gabon;
hInstitut de Recherche pour le Développement, Unité Mixte de Recherche 224 (Maladies Infectieuses et Vecteurs: Écologie, Génétique, Évolution et Contrôle), Institut de Recherche pour le Développement/Centre National de la Recherche Scientifique/Unité Mixte 1, 34032 Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: drosten@virology-bonn.de eric.leroy@ird.fr
Christian Drosten
aInstitute of Virology, University of Bonn Medical Centre, 53127 Bonn, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: drosten@virology-bonn.de eric.leroy@ird.fr
  1. Edited by Eckard Wimmer, Stony Brook University, Stony Brook, NY, and approved July 23, 2014 (received for review December 17, 2013)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

In 2010, a large outbreak of poliomyelitis involving 445 laboratory-confirmed cases occurred in the Republic of Congo. The 47% case-fatality rate was unusually high. Outbreak severity was attributed to low immunization coverage but vaccine-mediated immunity against the outbreak virus was never investigated. We isolated the poliovirus type 1 responsible for the outbreak and located its evolutionary origins to Southeast Asia. Fatal cases showed evidence for previous vaccination against polioviruses and the outbreak virus was refractive against neutralization by monoclonal and vaccine-derived antibodies. This pointed to immune escape contributing to the severity of the outbreak. Sustained vaccination regimens in polio-free regions, together with clinical and environmental poliovirus surveillance will be necessary to combat antigenetically variant polioviruses in the poliomyelitis eradication endgame.

Abstract

In 2010, a large outbreak of poliomyelitis with unusual 47% lethality occurred in Pointe Noire, Republic of Congo. Vaccine-mediated immunity against the outbreak virus was never investigated. A wild poliovirus 1 (WPV1) isolated from a fatal case (termed PV1-RC2010) showed a previously unknown combination of amino acid exchanges in critical antigenic site 2 (AgS2, VP1 capsid protein positions 221SAAL→221PADL). These exchanges were also detected in an additional 11 WPV1 strains from fatal cases. PV1-RC2010 escaped neutralization by three different mAbs relevant for AgS2. Virus neutralization was tested in sera from fatal cases, who died before supplementary immunization (n = 24), Gabonese recipients of recent oral polio vaccination (n = 12), routinely vaccinated German medical students (n = 34), and German outpatients tested for antipoliovirus immunity (n = 17) on Vero, human rhabdomyosarcoma, and human epidermoid carcinoma 2 cells. Fatal poliomyelitis cases gave laboratory evidence of previous trivalent vaccination. Neutralizing antibody titers against PV1-RC2010 were significantly lower than those against the vaccine strain Sabin-1, two genetically distinct WPV1s isolated in 1965 and 2010 and two genetically distinct vaccine-derived PV strains. Of German vaccinees tested according to World Health Organization protocols, 15–29% were unprotected according to their neutralization titers (<1:8 serum dilution), even though all were protected against Sabin-1. Phylogenetic analysis of the WPV1 outbreak strains suggested a recent introduction of virus progenitors from Asia with formation of separate Angolan and Congolese lineages. Only the latter carried both critical AgS2 mutations. Antigenetically variant PVs may become relevant during the final phase of poliomyelitis eradication in populations with predominantly vaccine-derived immunity. Sustained vaccination coverage and clinical and environmental surveillance will be necessary.

Footnotes

  • ↵1J.F.D., G.G., E.M.L., and C.D. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: drosten{at}virology-bonn.de or eric.leroy{at}ird.fr.
  • Author contributions: J.F.D., E.M.L., and C.D. designed research; J.F.D., G.G., A.N.L., L.I.K., S.B., G.U., J.R., S.E.L.-D., and S.D. performed research; G.G., A.P.G., R.T.-T., D.N., and M.K. contributed new reagents/analytic tools; J.F.D., A.N.L., A.M.E.-H., S.D., M.K., E.M.L., and C.D. analyzed data; and J.F.D., E.M.L., and C.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The nucleotide sequences reported in this paper have been deposited in the GenBank database (accession nos. JF838278–JF838290).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1323502111/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Poliovirus drift variant
Jan Felix Drexler, Gilda Grard, Alexander N. Lukashev, Liubov I. Kozlovskaya, Sindy Böttcher, Gökhan Uslu, Johan Reimerink, Anatoly P. Gmyl, Raphaël Taty-Taty, Sonia Etenna Lekana-Douki, Dieudonné Nkoghe, Anna M. Eis-Hübinger, Sabine Diedrich, Marion Koopmans, Eric M. Leroy, Christian Drosten
Proceedings of the National Academy of Sciences Sep 2014, 111 (35) 12889-12894; DOI: 10.1073/pnas.1323502111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Poliovirus drift variant
Jan Felix Drexler, Gilda Grard, Alexander N. Lukashev, Liubov I. Kozlovskaya, Sindy Böttcher, Gökhan Uslu, Johan Reimerink, Anatoly P. Gmyl, Raphaël Taty-Taty, Sonia Etenna Lekana-Douki, Dieudonné Nkoghe, Anna M. Eis-Hübinger, Sabine Diedrich, Marion Koopmans, Eric M. Leroy, Christian Drosten
Proceedings of the National Academy of Sciences Sep 2014, 111 (35) 12889-12894; DOI: 10.1073/pnas.1323502111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley

Article Classifications

  • Biological Sciences
  • Microbiology
Proceedings of the National Academy of Sciences: 111 (35)
Table of Contents

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Mouse fibroblast cells. Electron bifurcation reactions keep mammalian cells alive.
Exploring electron bifurcation
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490