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Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.
J Virol
December 2024
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
During the process by which human immunodeficiency virus (HIV-1) enters cells, the envelope glycoprotein (Env) trimer on the virion surface engages host cell receptors. Binding to the receptor CD4 induces Env to undergo transitions from a pretriggered, "closed" (State-1) conformation to more "open" (State 2/3) conformations. Most broadly neutralizing antibodies (bNAbs), which are difficult to elicit, recognize the pretriggered (State-1) conformation.
View Article and Find Full Text PDFSignal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.
Front Immunol
October 2024
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Article Synopsis
- The study focuses on the HIV-1 envelope (Env) protein, crucial for developing effective vaccines, and explores how the signal peptide (SP) affects its antigenicity (ability to trigger immune response) and immunogenicity (ability to induce an immune response).
- Researchers compared the Env proteins from two different HIV-1 isolates, assessing their natural forms and chimeras with swapped SPs, using various methods to evaluate their antigenicity and responses in mice.
- Results showed that swapping SPs influenced the antibodies' binding, with some chimeras showing improved immunogenicity, while the inclusion of DNA vaccines reduced the effectiveness of the wild-type proteins in generating a strong immune response.
Crimean Congo hemorrhagic fever virus nucleoprotein and GP38 subunit vaccine combination prevents morbidity in mice.
NPJ Vaccines
August 2024
Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Immunizing mice with Crimean-Congo hemorrhagic fever virus (CCHFV) nucleoprotein (NP), glycoprotein precursor (GPC), or with the GP38 domain of GPC, can be protective when the proteins are delivered with viral vectors or as a DNA or RNA vaccine. Subunit vaccines are a safe and cost-effective alternative to some vaccine platforms, but Gc and Gn glycoprotein subunit vaccines for CCHFV fail to protect despite eliciting high levels of neutralizing antibodies. Here, we investigated humoral and cellular immune responses and the protective efficacy of recombinant NP, GP38, and GP38 forms (GP85 and GP160) associated with the highly glycosylated mucin-like (MLD) domain, as well as the NP + GP38 combination.
View Article and Find Full Text PDFComparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.
J Virol
September 2024
Department of Integrative Immunobiology, Duke University School of Medicine, Durham, North Carolina, USA.
Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design.
View Article and Find Full Text PDFmRNA lipid nanoparticles expressing cell-surface cleavage independent HIV Env trimers elicit autologous tier-2 neutralizing antibodies.
Front Immunol
August 2024
Wyatt Lab, Department of Immunology and Microbiology, Scripps Research, La Jolla, CA, United States.
Article Synopsis
- - The HIV-1 envelope glycoprotein (Env) is crucial for the virus's ability to infect cells, requiring a specific cleavage process for its subunits to function in viral entry; a new method aims to enhance immunization strategies against HIV by genetically expressing a stable Env trimer on cell surfaces.
- - Researchers developed a 'native flexibly linked' (NFL) construct to simplify the expression of these HIV Env trimers without needing cleavage, ensuring they retain the right structure (native-like conformation) and can effectively stimulate the immune response.
- - The study shows that immunizing rabbits with mRNA lipid nanoparticles containing these membrane-bound stabilized Env trimers elicited strong neutralizing antibody responses, indicating potential for this genetic
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