Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo

Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1... Pandemic influenza A virus (H1N1) 2009 poses a serious public-health challenge worldwide. To characterize the neutralizing epitopes of this virus, we generated a panel of eight monoclonal antibodies (mAbs) against the HA of the A/California/07/2009 virus. The antibodies were specific for the 2009 pdm H1N1 HA, as the antibodies displayed HA-specific ELISA, hemagglutination inhibition (HAI) and neutralization activity. One mAb (mAb12) showed significantly higher HAI and neutralizing titers than the other mAbs. We mapped the antigenic epitopes of the HA by characterizing escape mutants of a 2009 H1N1 vaccine strain (NYMC X-179A). The amino acid changes suggested that these eight mAbs recognized HA antigenic epitopes located in the Sa, Sb, Ca1 and Ca2 sites. Passive immunization with mAbs showed that mAb12 displayed more efficient neutralizing activity in vivo than the other mAbs. mAb12 was also found to be protective, both prophylactically and therapeutically, against a lethal viral challenge in mice. In addition, a single injection of 10 mg/kg mAb12 outperformed a 5-day course of treatment with oseltamivir (10 mg/kg/day by gavage) with respect to both prophylaxis and treatment of lethal viral infection. Taken together, our results showed that mouse-origin mAbs displayed neutralizing effectiveness in vitro and in vivo . One mAb in particular (mAb12) recognized an epitope within the Sb site and demonstrated outstanding neutralizing effectiveness. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Evaluation of neutralizing efficacy of monoclonal antibodies specific for 2009 pandemic H1N1 influenza A virus in vitro and in vivo

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Publisher
Springer Vienna
Copyright
Copyright © 2014 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-013-1852-y
Publisher site
See Article on Publisher Site

References

  • Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic
    Smith, GJ; Vijaykrishna, D; Bahl, J; Lycett, SJ; Worobey, M; Pybus, OG; Ma, SK; Cheung, CL; Raghwani, J; Bhatt, S; Peiris, JS; Guan, Y; Rambaut, A
  • Influenza A/H1N1pdm virus in Russian Asia in 2009–2010
    Ilyicheva, T; Susloparov, I; Durymanov, A; Romanovskaya, A; Sharshov, K; Kurskaya, O; Ignashkina, M; Shestopalov, A
  • Prevention and treatment of bronchopneumonia in mice caused by mouse-adapted variant of avian H5N2 influenza A virus using monoclonal antibody against conserved epitope in the HA stem region
    Smirnov, YA; Lipatov, AS; Gitelman, AK; Claas, EC; Osterhaus, AD
  • Characterization of highly pathogenic H5N1 avian influenza viruses isolated from poultry markets in central China
    Chen, J; Fang, F; Yang, Z; Liu, X; Zhang, H; Zhang, Z; Zhang, X; Chen, Z
  • Escape mutants of pandemic influenza A/H1N1 2009 virus: variations in antigenic specificity and receptor affinity of the hemagglutinin
    Rudneva, I; Ignatieva, A; Timofeeva, T; Shilov, A; Kushch, A; Masalova, O; Klimova, R; Bovin, N; Mochalova, L; Kaverin, N

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