Optimization of human immunodeficiency virus Gag expression by newcastle disease virus vectors for the induction of potent immune responses

Elena Carnero, Wenjing Li, Antonio V. Borderia, Bruno Moltedo, Thomas Moran, Adolfo García-Sastre

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8 + T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.

Original languageEnglish
Pages (from-to)584-597
Number of pages14
JournalJournal of Virology
Volume83
Issue number2
DOIs
Publication statusPublished - Jan 2009
Externally publishedYes

Fingerprint

Disease Vectors
Virus Activation
Newcastle disease virus
HIV
Viruses
Antigens
Codon
Human Immunodeficiency Virus gag Gene Products
Immunity
Vaccines
Vaccinia virus
Viral Genome
Eggs
Chickens
Animal Models
Genome
T-Lymphocytes
Safety

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Optimization of human immunodeficiency virus Gag expression by newcastle disease virus vectors for the induction of potent immune responses. / Carnero, Elena; Li, Wenjing; Borderia, Antonio V.; Moltedo, Bruno; Moran, Thomas; García-Sastre, Adolfo.

In: Journal of Virology, Vol. 83, No. 2, 01.2009, p. 584-597.

Research output: Contribution to journalArticle

Carnero, Elena ; Li, Wenjing ; Borderia, Antonio V. ; Moltedo, Bruno ; Moran, Thomas ; García-Sastre, Adolfo. / Optimization of human immunodeficiency virus Gag expression by newcastle disease virus vectors for the induction of potent immune responses. In: Journal of Virology. 2009 ; Vol. 83, No. 2. pp. 584-597.
@article{4194618f2a9f4d1b9af359d2edb69b8e,
title = "Optimization of human immunodeficiency virus Gag expression by newcastle disease virus vectors for the induction of potent immune responses",
abstract = "One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8 + T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.",
author = "Elena Carnero and Wenjing Li and Borderia, {Antonio V.} and Bruno Moltedo and Thomas Moran and Adolfo Garc{\'i}a-Sastre",
year = "2009",
month = "1",
doi = "10.1128/JVI.01443-08",
language = "English",
volume = "83",
pages = "584--597",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Optimization of human immunodeficiency virus Gag expression by newcastle disease virus vectors for the induction of potent immune responses

AU - Carnero, Elena

AU - Li, Wenjing

AU - Borderia, Antonio V.

AU - Moltedo, Bruno

AU - Moran, Thomas

AU - García-Sastre, Adolfo

PY - 2009/1

Y1 - 2009/1

N2 - One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8 + T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.

AB - One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8 + T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.

UR - http://www.scopus.com/inward/record.url?scp=58149526762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149526762&partnerID=8YFLogxK

U2 - 10.1128/JVI.01443-08

DO - 10.1128/JVI.01443-08

M3 - Article

C2 - 19004953

AN - SCOPUS:58149526762

VL - 83

SP - 584

EP - 597

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -