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

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TitleBiochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus.
Publication TypeJournal Article
Year of Publication2005
AuthorsForsell, MNE, Li, Y, Sundbäck, M, Svehla, K, Liljeström, P, Mascola, JR, Wyatt, R, Hedestam, GBKarlsson
JournalJ Virol
Volume79
Issue17
Pagination10902-14
Date Published2005 Sep
ISSN0022-538X
KeywordsAIDS Vaccines, Animals, Cells, Cultured, env Gene Products, Human Immunodeficiency Virus, 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
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.

DOI10.1128/JVI.79.17.10902-10914.2005
Alternate JournalJ. Virol.
PubMed ID16103142
PubMed Central IDPMC1193613