The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses derived from a phage display immune library

Nina Tikunova, Viktoriya Dubrovskaya, Vera Morozova, Tatiana Yun, Yana Khlusevich, Nikolai Bormotov, Aleksandr Laman, Fedor Brovko, Aleksandr Shvalov, Eugeni Belanov

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

A panel of recombinant human antibodies to orthopoxviruses was isolated from a combinatorial phage display library of human scFv antibodies constructed from the Vh and Vl genes cloned from the peripheral blood lymphocytes of Vaccinia virus (VACV) immune donors. Plaque-reduction neutralization tests showed that seven selected phage-displaying scFv antibodies (pdAbs) neutralized both CPXV and VACV, and five of them neutralized Monkeypox virus (MPXV). Western blot analysis of VACV and CPXV proteins demonstrated that seven neutralizing antibodies recognized a 35kDa protein. To identify this target protein, we produced a recombinant J3L protein of CPXV and showed that all the selected neutralizing antibodies recognized this protein. Neutralizing pdAb b9 was converted into fully human mAb b9 (fh b9), and scFv b9 displayed high binding affinities (K d of 0.7 and 3.2nM). The fh b9 reduced VACV plaque formation in a dose-dependent manner.

Original languageEnglish (US)
Pages (from-to)141-150
Number of pages10
JournalVirus Research
Volume163
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Cowpox virus
  • Fully human mAb
  • Monkeypox virus
  • Neutralization
  • Phage display
  • ScFv
  • Vaccinia virus

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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