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Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.

Publication ,  Journal Article
Khattar, SK; Samal, S; LaBranche, CC; Montefiori, DC; Collins, PL; Samal, SK
Published in: PLoS One
2013

The development of a vaccine against human immunodeficiency virus-1 (HIV-1) capable of inducing broad humoral and cellular responses at both the systemic and mucosal levels will be critical for combating the global AIDS epidemic. We previously demonstrated the ability of Newcastle disease virus (NDV) as a vaccine vector to express oligomeric Env protein gp160 and induce potent humoral and mucosal immune responses. In the present study, we used NDV vaccine strain LaSota as a vector to compare the biochemical and immunogenic properties of vector-expressed gp160, gp120, and two versions of gp140 (a derivative of gp160 made by deleting the transmembrane and cytoplasmic domains), namely: gp140L, which contained the complete membrane-proximal external region (MPER), and gp140S, which lacks the distal half of MPER. We show that, similar to gp160, NDV-expressed gp140S and gp120, but not gp140L, formed higher-order oligomers that retained recognition by conformationally sensitive monoclonal antibodies. Immunization of guinea pigs by the intranasal route with rLaSota/gp140S resulted in significantly greater systemic and mucosal antibody responses compared to the other recombinants. Immunization with rLaSota/140S, rLaSota/140L rLaSota/120 resulted in mixed Th1/Th2 immune responses as compared to Th1-biased immune responses induced by rLaSota/160. Importantly, rLaSota/gp140S induced neutralizing antibody responses to homologous HIV-1 strain BaL.26 and laboratory adapted HIV-1 strain MN.3 that were stronger than those elicited by the other NDV recombinants. Additionally, rLaSota/gp140S induced greater CD4+ and CD8+ T-cell responses in mice. These studies illustrate that rLaSota/gp140S is a promising vaccine candidate to elicit potent mucosal, humoral and cellular immune responses to the HIV-1 Env protein.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

10

Start / End Page

e78521

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines, Attenuated
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Engineering
  • Newcastle disease virus
  • Mice, Inbred BALB C
  • Mice
  • Immunity, Mucosal
  • Immunity, Humoral
 

Citation

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Chicago
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MLA
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Khattar, S. K., Samal, S., LaBranche, C. C., Montefiori, D. C., Collins, P. L., & Samal, S. K. (2013). Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector. PLoS One, 8(10), e78521. https://doi.org/10.1371/journal.pone.0078521
Khattar, Sunil K., Sweety Samal, Celia C. LaBranche, David C. Montefiori, Peter L. Collins, and Siba K. Samal. “Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.PLoS One 8, no. 10 (2013): e78521. https://doi.org/10.1371/journal.pone.0078521.
Khattar SK, Samal S, LaBranche CC, Montefiori DC, Collins PL, Samal SK. Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector. PLoS One. 2013;8(10):e78521.
Khattar, Sunil K., et al. “Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.PLoS One, vol. 8, no. 10, 2013, p. e78521. Pubmed, doi:10.1371/journal.pone.0078521.
Khattar SK, Samal S, LaBranche CC, Montefiori DC, Collins PL, Samal SK. Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector. PLoS One. 2013;8(10):e78521.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

10

Start / End Page

e78521

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccines, Attenuated
  • Recombinant Proteins
  • Protein Structure, Tertiary
  • Protein Engineering
  • Newcastle disease virus
  • Mice, Inbred BALB C
  • Mice
  • Immunity, Mucosal
  • Immunity, Humoral