Improved NYVAC-based vaccine vectors

Karen Kibler, Carmen E. Gomez, Beatriz Perdiguero, Shukmei Wong, Trung Huynh, Susan Holechek, William Arndt, Victoria Jimenez, Ruben Gonzalez-Sanz, Karen Denzler, Elias K. Haddad, Ralf Wagner, Rafick P. Sékaly, James Tartaglia, Giuseppe Pantaleo, Bertram Jacobs, Mariano Esteban

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

Original languageEnglish (US)
Article numbere25674
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 9 2011

Fingerprint

vector vaccines
Viruses
Vaccines
viruses
Poxviridae
Combined Vaccines
AIDS Vaccines
Interferon Type I
Vaccinia virus
Host Specificity
Virus Replication
vaccines
Keratinocytes
Genes
Signal Transduction
keratinocytes
Acquired Immunodeficiency Syndrome
interferons
Fibroblasts
Signal transduction

ASJC Scopus subject areas

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

Cite this

Kibler, K., Gomez, C. E., Perdiguero, B., Wong, S., Huynh, T., Holechek, S., ... Esteban, M. (2011). Improved NYVAC-based vaccine vectors. PLoS One, 6(11), [e25674]. https://doi.org/10.1371/journal.pone.0025674

Improved NYVAC-based vaccine vectors. / Kibler, Karen; Gomez, Carmen E.; Perdiguero, Beatriz; Wong, Shukmei; Huynh, Trung; Holechek, Susan; Arndt, William; Jimenez, Victoria; Gonzalez-Sanz, Ruben; Denzler, Karen; Haddad, Elias K.; Wagner, Ralf; Sékaly, Rafick P.; Tartaglia, James; Pantaleo, Giuseppe; Jacobs, Bertram; Esteban, Mariano.

In: PLoS One, Vol. 6, No. 11, e25674, 09.11.2011.

Research output: Contribution to journalArticle

Kibler, K, Gomez, CE, Perdiguero, B, Wong, S, Huynh, T, Holechek, S, Arndt, W, Jimenez, V, Gonzalez-Sanz, R, Denzler, K, Haddad, EK, Wagner, R, Sékaly, RP, Tartaglia, J, Pantaleo, G, Jacobs, B & Esteban, M 2011, 'Improved NYVAC-based vaccine vectors', PLoS One, vol. 6, no. 11, e25674. https://doi.org/10.1371/journal.pone.0025674
Kibler K, Gomez CE, Perdiguero B, Wong S, Huynh T, Holechek S et al. Improved NYVAC-based vaccine vectors. PLoS One. 2011 Nov 9;6(11). e25674. https://doi.org/10.1371/journal.pone.0025674
Kibler, Karen ; Gomez, Carmen E. ; Perdiguero, Beatriz ; Wong, Shukmei ; Huynh, Trung ; Holechek, Susan ; Arndt, William ; Jimenez, Victoria ; Gonzalez-Sanz, Ruben ; Denzler, Karen ; Haddad, Elias K. ; Wagner, Ralf ; Sékaly, Rafick P. ; Tartaglia, James ; Pantaleo, Giuseppe ; Jacobs, Bertram ; Esteban, Mariano. / Improved NYVAC-based vaccine vectors. In: PLoS One. 2011 ; Vol. 6, No. 11.
@article{03df33f0ed88496ead5477adcbc7d3a4,
title = "Improved NYVAC-based vaccine vectors",
abstract = "While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.",
author = "Karen Kibler and Gomez, {Carmen E.} and Beatriz Perdiguero and Shukmei Wong and Trung Huynh and Susan Holechek and William Arndt and Victoria Jimenez and Ruben Gonzalez-Sanz and Karen Denzler and Haddad, {Elias K.} and Ralf Wagner and S{\'e}kaly, {Rafick P.} and James Tartaglia and Giuseppe Pantaleo and Bertram Jacobs and Mariano Esteban",
year = "2011",
month = "11",
day = "9",
doi = "10.1371/journal.pone.0025674",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - Improved NYVAC-based vaccine vectors

AU - Kibler, Karen

AU - Gomez, Carmen E.

AU - Perdiguero, Beatriz

AU - Wong, Shukmei

AU - Huynh, Trung

AU - Holechek, Susan

AU - Arndt, William

AU - Jimenez, Victoria

AU - Gonzalez-Sanz, Ruben

AU - Denzler, Karen

AU - Haddad, Elias K.

AU - Wagner, Ralf

AU - Sékaly, Rafick P.

AU - Tartaglia, James

AU - Pantaleo, Giuseppe

AU - Jacobs, Bertram

AU - Esteban, Mariano

PY - 2011/11/9

Y1 - 2011/11/9

N2 - While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

AB - While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

UR - http://www.scopus.com/inward/record.url?scp=80655128531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80655128531&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0025674

DO - 10.1371/journal.pone.0025674

M3 - Article

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e25674

ER -