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Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus

Academic Article
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Overview

authors

  • Forsell, M. N. E.
  • Li, Yuxing
  • Sundback, M.
  • Svehla, K.
  • Liljestrom, P.
  • Mascola, J. R.
  • Wyatt, Richard
  • Hedestam, G. B. K.

publication date

  • September 2005

journal

  • Journal of Virology  Journal

abstract

  • The current lack of envelope glycoprotein immunogens that elicit broadly neutralizing antibody responses remains a major challenge for human immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent design and construction of stable soluble gp140 trimers have shown that some neutralization breadth can be achieved by using immunogens that better mimic the functional viral spike complex. The use of genetic delivery systems to drive the in vivo expression of such immunogens for the stimulation of neutralizing antibodies against HIV-1 may offer advantages by maintaining the quaternary structure of the trimeric envelope glycoproteins. Here, we describe the biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein trimers expressed by recombinant Semliki Forest virus (rSFV). The results presented here demonstrate that rSFV supports the expression of stable soluble gp140 trimers that retain recognition by conformationally sensitive antibodies. Further, we show that rSFV particle immunizations efficiently primed immune responses as measured after a single boost with purified trimeric gp140 protein, resulting in a Th1-biased antibody response. This differed from the Th2-biased antibody response obtained after repeated immunizations with purified gp140 protein trimers. Despite this difference, both regimens stimulated neutralizing antibody responses of similar potency. This suggests that rSFV may be a useful component of a viral vector prime-protein boost regimen aimed at stimulating both cell-mediated immune responses and neutralizing antibodies against HIV-1.

subject areas

  • AIDS Vaccines
  • Animals
  • Cells, Cultured
  • Female
  • Gene Products, env
  • HIV Antibodies
  • HIV Infections
  • Immunization
  • Immunization Schedule
  • Lymphocyte Count
  • Mice
  • Neutralization Tests
  • Rabbits
  • Semliki forest virus
  • Solubility
  • Spleen
  • Th1 Cells
  • Vaccines, Synthetic
  • env Gene Products, Human Immunodeficiency Virus
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Identity

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.79.17.10902-10914.2005

PubMed ID

  • 16103142
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Additional Document Info

start page

  • 10902

end page

  • 10914

volume

  • 79

issue

  • 17

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