Membrane embedded HIV-1 envelope on the surface of a virus-like particle elicits broader immune responses than soluble envelopes
| Autor: | Ted M. Ross, Sean P. McBurney, Kelly R. Young |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Env
Cellular immunity viruses HIV Infections HIV Antibodies HIV Envelope Protein gp120 Biology Gp41 Mice Immune system Viral Envelope Proteins Virus-like particle Neutralization Tests VLP Virology Animals Administration Intranasal Immunization Schedule AIDS Vaccines Antiserum Mice Inbred BALB C Vaccines Synthetic Virion env Gene Products Human Immunodeficiency Virus Gene Products env HIV virus diseases biochemical phenomena metabolism and nutrition Mucosal vaccination Long terminal repeat Immunoglobulin A Titer Immunoglobulin G HIV-1 biology.protein Female Immunization Antibody Vaccine Plasmids |
| Zdroj: | Virology. 358:334-346 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2006.08.032 |
| Popis: | Virally regulated HIV-1 particles were expressed from DNA plasmids encoding Gag, protease, reverse transcriptase, Vpu, Tat, Rev, and Env. The sequences for integrase, Vpr, Vif, Nef, and the long terminal repeats (LTRs) were deleted. Mutations were engineered into the VLP genome to produce particles deficient in activities associated with viral reverse transcriptase, RNase H, and RNA packaging. Each plasmid efficiently secreted particles from primate cells in vitro and particles were purified from the supernatants and used as immunogens. Mice (BALB/c) were vaccinated intranasally (day 1 and weeks 3 and 6) with purified VLPs and the elicited immunity was compared to particles without Env (Gagp55), to soluble monomeric Envgp120, or to soluble trimerized Envgp140. Only mice vaccinated with VLPs had robust anti-Env cellular immunity. In contrast, all mice had high titer anti-Env serum antibody (IgG). However, VLP-vaccinated mice had antisera that detected a broader number of linear Env peptides, had anti-Env mucosal IgA and IgG, as well as higher titers of serum neutralizing antibodies. VLPs elicited high titer antibodies that recognized linear regions in V4-C5 and the ectodomain of gp41, but did not recognize V3. These lentiviral VLPs are effective mucosal immunogens that elicit broader immunity against Env determinants in both the systemic and mucosal immune compartments than soluble forms of Env. |
| Databáze: | OpenAIRE |
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