The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization

Olga V. Masalova; Ekaterina I. Lesnova; Alexei V. Pichugin; Tatiana M. Melnikova; Vadim V. Grabovetsky; Natalia V. Petrakova; Olga A. Smirnova; Alexander V. Ivanov; Alexei D. Zaberezhny; Ravshan I. Ataullakhanov; Maria G. Isaguliants; Alla A. Kushch

doi:10.1016/j.vaccine.2009.10.097

The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization

Olga V. Masalova (Corresponding Author)
, Ekaterina I. Lesnova
, Alexei V. Pichugin
, Tatiana M. Melnikova
, Vadim V. Grabovetsky
, Natalia V. Petrakova
, Olga A. Smirnova
, Alexander V. Ivanov
, Alexei D. Zaberezhny
, Ravshan I. Ataullakhanov
, Maria G. Isaguliants (Corresponding Author)
, Alla A. Kushch

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax^®. The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-γ. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4⁺ and CD8⁺ T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.

Original language	English
Pages (from-to)	1987-1996
Number of pages	10
Journal	Vaccine
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/j.vaccine.2009.10.097
Publication status	Published - 23 Feb 2010
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords*

Adjuvant
DNA immunization
HCV vaccine
Hepatitis C virus
Heterologous prime-boost
Immunomax
Nonstructural protein 5A (NS5A)
Promiscuous T-cell epitopes

Field of Science*

1.6 Biological sciences
3.1 Basic medicine
3.3 Health sciences

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1016/j.vaccine.2009.10.097

Cite this

Masalova, O. V., Lesnova, E. I., Pichugin, A. V., Melnikova, T. M., Grabovetsky, V. V., Petrakova, N. V., Smirnova, O. A., Ivanov, A. V., Zaberezhny, A. D., Ataullakhanov, R. I., Isaguliants, M. G., & Kushch, A. A. (2010). The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization. Vaccine , 28(8), 1987-1996. https://doi.org/10.1016/j.vaccine.2009.10.097

@article{dd8490c4d8644a39b1c73280c9bacce0,

title = "The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization",

abstract = "The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax{\textregistered}. The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-γ. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4+ and CD8+ T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.",

keywords = "Adjuvant, DNA immunization, HCV vaccine, Hepatitis C virus, Heterologous prime-boost, Immunomax, Nonstructural protein 5A (NS5A), Promiscuous T-cell epitopes",

author = "Masalova, \{Olga V.\} and Lesnova, \{Ekaterina I.\} and Pichugin, \{Alexei V.\} and Melnikova, \{Tatiana M.\} and Grabovetsky, \{Vadim V.\} and Petrakova, \{Natalia V.\} and Smirnova, \{Olga A.\} and Ivanov, \{Alexander V.\} and Zaberezhny, \{Alexei D.\} and Ataullakhanov, \{Ravshan I.\} and Isaguliants, \{Maria G.\} and Kushch, \{Alla A.\}",

note = "Funding Information: Authors wish to express a sincere gratitude to Dr. R. Bartenschlager (Heidelberg, Germany) for the gift of the plasmid pTM 3420-9396. Russian Foundation for Basic Research, grant 08-04-01107, Federal Agency for Science and Innovation, grant 02.512.11.2291, Swedish Research Council \#K2009-66X-21053-01-3; and the New Visby program of the Swedish Institute are gratefully acknowledged for the financial support.",

year = "2010",

month = feb,

day = "23",

doi = "10.1016/j.vaccine.2009.10.097",

language = "English",

volume = "28",

pages = "1987--1996",

journal = "Vaccine ",

issn = "0264-410X",

publisher = "Elsevier Ltd.",

number = "8",

}

Masalova, OV, Lesnova, EI, Pichugin, AV, Melnikova, TM, Grabovetsky, VV, Petrakova, NV, Smirnova, OA, Ivanov, AV, Zaberezhny, AD, Ataullakhanov, RI, Isaguliants, MG & Kushch, AA 2010, 'The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization', Vaccine , vol. 28, no. 8, pp. 1987-1996. https://doi.org/10.1016/j.vaccine.2009.10.097

TY - JOUR

T1 - The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization

AU - Masalova, Olga V.

AU - Lesnova, Ekaterina I.

AU - Pichugin, Alexei V.

AU - Melnikova, Tatiana M.

AU - Grabovetsky, Vadim V.

AU - Petrakova, Natalia V.

AU - Smirnova, Olga A.

AU - Ivanov, Alexander V.

AU - Zaberezhny, Alexei D.

AU - Ataullakhanov, Ravshan I.

AU - Isaguliants, Maria G.

AU - Kushch, Alla A.

N1 - Funding Information: Authors wish to express a sincere gratitude to Dr. R. Bartenschlager (Heidelberg, Germany) for the gift of the plasmid pTM 3420-9396. Russian Foundation for Basic Research, grant 08-04-01107, Federal Agency for Science and Innovation, grant 02.512.11.2291, Swedish Research Council #K2009-66X-21053-01-3; and the New Visby program of the Swedish Institute are gratefully acknowledged for the financial support.

PY - 2010/2/23

Y1 - 2010/2/23

N2 - The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax®. The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-γ. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4+ and CD8+ T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.

AB - The aim of this study was to evaluate the immunogenicity of NS5A protein of human hepatitis C virus (HCV) when delivered as naked DNA (NS5A DNA), or recombinant protein (rNS5A). DBA/2J mice received NS5A DNA, rNS5A, or NS5A DNA/rNS5A in different prime-boost combinations with a peptidoglycan Immunomax®. The weakest response was induced after rNS5A prime and NS5A DNA boost; rNS5A alone induced an immune response with a strong Th2-component; and NS5A DNA alone, a relatively weak secretion of IL-2 and IFN-γ. The most efficient was co-injection of NS5A DNA and rNS5A, which induced a significant increase in CD4+ and CD8+ T-cell counts, anti-NS5A antibodies, specific T-cell proliferation, and proinflammatory cytokine production in vitro against a broad spectrum of NS5A epitopes. Administration of the mixture of adjuvanted DNA and protein immunogens can be selected as the best regimen for further preclinical HCV-vaccine trials.

KW - Adjuvant

KW - DNA immunization

KW - HCV vaccine

KW - Hepatitis C virus

KW - Heterologous prime-boost

KW - Immunomax

KW - Nonstructural protein 5A (NS5A)

KW - Promiscuous T-cell epitopes

UR - https://www.scopus.com/pages/publications/76949095182

U2 - 10.1016/j.vaccine.2009.10.097

DO - 10.1016/j.vaccine.2009.10.097

M3 - Article

C2 - 20188254

AN - SCOPUS:76949095182

SN - 0264-410X

VL - 28

SP - 1987

EP - 1996

JO - Vaccine

JF - Vaccine

IS - 8

ER -

The successful immune response against hepatitis C nonstructural protein 5A (NS5A) requires heterologous DNA/protein immunization

Abstract

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Keywords*

Field of Science*

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