Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors

Esther D. Quakkelaar, Anke Redeker, Elias K. Haddad, Alexandre Harari, Stella Mayo McCaughey, Thomas Duhen, Abdelali Filali-Mouhim, Jean Philippe Goulet, Nikki M. Loof, Ferry Ossendorp, Beatriz Perdiguero, Paul Heinen, Carmen E. Gomez, Karen Kibler, David M. Koelle, Rafick P. Sékaly, Federica Sallusto, Antonio Lanzavecchia, Giuseppe Pantaleo, Mariano Esteban & 3 others Jim Tartaglia, Bertram Jacobs, Cornelis J M Melief

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

Original languageEnglish (US)
Article numbere16819
JournalPLoS One
Volume6
Issue number2
DOIs
StatePublished - 2011

Fingerprint

immunostimulation (physiological)
Human Immunodeficiency Virus Proteins
Poxviridae
T-cells
interferons
Human immunodeficiency virus 1
Interferons
Antigen Presentation
HIV-1
Immunization
Interferon Type I
Gene encoding
Genes
HIV
Antigens
dendritic cells
Cross-Priming
Dendritic Cells
Carrier Proteins
T-lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Quakkelaar, E. D., Redeker, A., Haddad, E. K., Harari, A., McCaughey, S. M., Duhen, T., ... Melief, C. J. M. (2011). Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. PLoS One, 6(2), [e16819]. https://doi.org/10.1371/journal.pone.0016819

Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. / Quakkelaar, Esther D.; Redeker, Anke; Haddad, Elias K.; Harari, Alexandre; McCaughey, Stella Mayo; Duhen, Thomas; Filali-Mouhim, Abdelali; Goulet, Jean Philippe; Loof, Nikki M.; Ossendorp, Ferry; Perdiguero, Beatriz; Heinen, Paul; Gomez, Carmen E.; Kibler, Karen; Koelle, David M.; Sékaly, Rafick P.; Sallusto, Federica; Lanzavecchia, Antonio; Pantaleo, Giuseppe; Esteban, Mariano; Tartaglia, Jim; Jacobs, Bertram; Melief, Cornelis J M.

In: PLoS One, Vol. 6, No. 2, e16819, 2011.

Research output: Contribution to journalArticle

Quakkelaar, ED, Redeker, A, Haddad, EK, Harari, A, McCaughey, SM, Duhen, T, Filali-Mouhim, A, Goulet, JP, Loof, NM, Ossendorp, F, Perdiguero, B, Heinen, P, Gomez, CE, Kibler, K, Koelle, DM, Sékaly, RP, Sallusto, F, Lanzavecchia, A, Pantaleo, G, Esteban, M, Tartaglia, J, Jacobs, B & Melief, CJM 2011, 'Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors', PLoS One, vol. 6, no. 2, e16819. https://doi.org/10.1371/journal.pone.0016819
Quakkelaar, Esther D. ; Redeker, Anke ; Haddad, Elias K. ; Harari, Alexandre ; McCaughey, Stella Mayo ; Duhen, Thomas ; Filali-Mouhim, Abdelali ; Goulet, Jean Philippe ; Loof, Nikki M. ; Ossendorp, Ferry ; Perdiguero, Beatriz ; Heinen, Paul ; Gomez, Carmen E. ; Kibler, Karen ; Koelle, David M. ; Sékaly, Rafick P. ; Sallusto, Federica ; Lanzavecchia, Antonio ; Pantaleo, Giuseppe ; Esteban, Mariano ; Tartaglia, Jim ; Jacobs, Bertram ; Melief, Cornelis J M. / Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. In: PLoS One. 2011 ; Vol. 6, No. 2.
@article{48d0d04fd1e344c6aebb21d978a9bf1e,
title = "Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors",
abstract = "Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.",
author = "Quakkelaar, {Esther D.} and Anke Redeker and Haddad, {Elias K.} and Alexandre Harari and McCaughey, {Stella Mayo} and Thomas Duhen and Abdelali Filali-Mouhim and Goulet, {Jean Philippe} and Loof, {Nikki M.} and Ferry Ossendorp and Beatriz Perdiguero and Paul Heinen and Gomez, {Carmen E.} and Karen Kibler and Koelle, {David M.} and S{\'e}kaly, {Rafick P.} and Federica Sallusto and Antonio Lanzavecchia and Giuseppe Pantaleo and Mariano Esteban and Jim Tartaglia and Bertram Jacobs and Melief, {Cornelis J M}",
year = "2011",
doi = "10.1371/journal.pone.0016819",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors

AU - Quakkelaar, Esther D.

AU - Redeker, Anke

AU - Haddad, Elias K.

AU - Harari, Alexandre

AU - McCaughey, Stella Mayo

AU - Duhen, Thomas

AU - Filali-Mouhim, Abdelali

AU - Goulet, Jean Philippe

AU - Loof, Nikki M.

AU - Ossendorp, Ferry

AU - Perdiguero, Beatriz

AU - Heinen, Paul

AU - Gomez, Carmen E.

AU - Kibler, Karen

AU - Koelle, David M.

AU - Sékaly, Rafick P.

AU - Sallusto, Federica

AU - Lanzavecchia, Antonio

AU - Pantaleo, Giuseppe

AU - Esteban, Mariano

AU - Tartaglia, Jim

AU - Jacobs, Bertram

AU - Melief, Cornelis J M

PY - 2011

Y1 - 2011

N2 - Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

AB - Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.

UR - http://www.scopus.com/inward/record.url?scp=79951911508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951911508&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0016819

DO - 10.1371/journal.pone.0016819

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e16819

ER -