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

doi:10.1016/j.virusres.2011.09.008

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 journal › Article › peer-review

11 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 language	English (US)
Pages (from-to)	141-150
Number of pages	10
Journal	Virus Research
Volume	163
Issue number	1
DOIs	https://doi.org/10.1016/j.virusres.2011.09.008
State	Published - Jan 2012
Externally published	Yes

Keywords

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

ASJC Scopus subject areas

Infectious Diseases
Cancer Research
Virology

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10.1016/j.virusres.2011.09.008

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title = "The neutralizing human recombinant antibodies to pathogenic Orthopoxviruses derived from a phage display immune library",

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.",

keywords = "Cowpox virus, Fully human mAb, Monkeypox virus, Neutralization, Phage display, ScFv, Vaccinia virus",

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

note = "Funding Information: Authors thank Professor Alexandr A. Ilyichev for fruitful discussion of this study. This work was supported in part by The International Science & Technology Center Grant #1638p and Russian Federal Science & Technology Program Grant # 43.035.1.1.1527 .",

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AU - Tikunova, Nina

AU - Dubrovskaya, Viktoriya

AU - Morozova, Vera

AU - Yun, Tatiana

AU - Khlusevich, Yana

AU - Bormotov, Nikolai

AU - Laman, Aleksandr

AU - Brovko, Fedor

AU - Shvalov, Aleksandr

AU - Belanov, Eugeni

N1 - Funding Information: Authors thank Professor Alexandr A. Ilyichev for fruitful discussion of this study. This work was supported in part by The International Science & Technology Center Grant #1638p and Russian Federal Science & Technology Program Grant # 43.035.1.1.1527 .

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N2 - 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.

AB - 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.

KW - Cowpox virus

KW - Fully human mAb

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KW - Neutralization

KW - Phage display

KW - ScFv

KW - Vaccinia virus

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

Abstract

Keywords

ASJC Scopus subject areas

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