ArticleRetrovirology2011
A stabilized HIV-1 envelope glycoprotein trimer fused to CD40 ligand targets and activates dendritic cells.
Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
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- Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry.iScience · 2022Article
- New Approaches to Dendritic Cell-Based Therapeutic Vaccines Against HIV-1 Infection.Frontiers in immunology · 2021Review
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- Engineering and Characterization of a Fluorescent Native-Like HIV-1 Envelope Glycoprotein Trimer.Biomolecules · 2015Article
- Immunosilencing a highly immunogenic protein trimerization domain.The Journal of biological chemistry · 2015Article
- Autoantibodies induced by chimeric cytokine-HIV envelope glycoprotein immunogens.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Article
- HIV-1 adenoviral vector vaccines expressing multi-trimeric BAFF and 4-1BBL enhance T cell mediated anti-viral immunity.PloS one · 2014Article
- T cell responses to viral infections - opportunities for Peptide vaccination.Frontiers in immunology · 2014Review
- Elicitation of HIV-1-neutralizing antibodies against the CD4-binding site.Current opinion in HIV and AIDS · 2013Review
- A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies.PLoS pathogens · 2013Article
- Article
- Designing a soluble near full-length HIV-1 gp41 trimer.The Journal of biological chemistry · 2013Article
- Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers.PloS one · 2013Article
- An HIV-1 envelope glycoprotein trimer with an embedded IL-21 domain activates human B cells.PloS one · 2013Article
- Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF) activity.PloS one · 2013Article
- Targeting HIV-1 envelope glycoprotein trimers to B cells by using APRIL improves antibody responses.Journal of virology · 2012Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOne reason why subunit protein and DNA vaccines are often less immunogenic than live-attenuated and whole-inactivated virus vaccines is that they lack the co-stimulatory signals provided by various components of the more complex vaccines. The HIV-1 envelope glycoprotein complex (Env) is no exception to this rule. Other factors that limit the induction of neutralizing antibodies against HIV-1 lie in the structure and instability of Env. We have previously stabilized soluble trimeric mimics of Env by introducing a disulfide bond between gp120 and gp41 and adding a trimer stabilizing mutation in gp41 (SOSIP.R6 gp140).
resultsWe further stabilized the SOSIP.R6 gp140 using a GCN4-based isoleucine zipper motif, creating SOSIP.R6-IZ gp140. In order to target SOSIP.R6-IZ to immune cells, including dendritic cells, while at the same time activating these cells, we fused SOSIP.R6-IZ to the active domain of CD40 ligand (CD40L), which may serve as a 'cis-adjuvant'. The Env component of the SOSIP.R6-IZ-CD40L fusion construct bound to CD4 and neutralizing antibodies, while the CD40L moiety interacted with CD40. Furthermore, the chimeric molecule was able to signal efficiently through CD40 and induce maturation of human dendritic cells. Dendritic cells secreted IL-6, IL-10 and IL-12 in response to stimulation by SOSIP.R6-IZ-CD40L and were able to activate naïve T cells.
conclusionsChimeric HIV-1 gp140 - CD40L trimers can target and activate dendritic cells. Targeting and activating immune cells using CD40L and other 'cis-adjuvants' may improve subunit protein vaccine immunogenicity for HIV-1 and other infectious diseases.
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