A5046694302- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Herpesvirus Infections and Treatments
- Influenza Virus Research Studies
- Glycosylation and Glycoproteins Research
- Animal Disease Management and Epidemiology
- vaccines and immunoinformatics approaches
- Click Chemistry and Applications
- Respiratory viral infections research
- Virology and Viral Diseases
- Chemical Synthesis and Analysis
Boehringer Ingelheim (United States)
2021-2023
Novartis (Switzerland)
2013
Dana-Farber Cancer Institute
2003-2011
Harvard University
2003-2011
Novartis (United States)
2011
Global Vaccines (United States)
2011
Binding to the CD4 receptor induces conformational changes in human immunodeficiency virus (HIV-1) gp120 exterior envelope glycoprotein. These allow bind coreceptor, either CCR5 or CXCR4, and prime gp41 transmembrane glycoprotein mediate virus-cell membrane fusion entry. Soluble forms of (sCD4) small-molecule mimics (here exemplified by JRC-II-191) also induce these HIV-1 glycoproteins, but typically inhibit entry into CD4-expressing cells. To investigate mechanism inhibition, we monitored...
Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing lack have been generated laboratory. These CD4-independent are sensitive to neutralization multiple antibodies recognize different epitopes. The mechanisms underlying independence, global sensitivity association...
ABSTRACT Binding to the primary receptor CD4 induces conformational changes in human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by gp41 transmembrane glycoprotein. Here we report derivation of an HIV-1 variant, H66N, confers resistance temperature extremes. The H66N change decreases spontaneous sampling CD4-bound conformation glycoproteins, thus diminishing...
ABSTRACT The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein trimer consists of gp120 and gp41 subunits undergoes a series conformational changes upon binding to the receptors, CD4 CCR5/CXCR4, that promote entry. Surprisingly, we found glycoproteins some HIV-1 strains are functionally inactivated by prolonged incubation on ice. Serial exposure extremes temperature, followed expansion replication-competent viruses, allowed selection temperature-resistant virus. this resisted...
Vaccines are an essential tool for the control of viral infections in domestic animals. We generated recombinant vector herpesvirus turkeys (vHVT) vaccines expressing computationally optimized broadly reactive antigen (COBRA) H5 avian influenza virus (AIV) alone (vHVT-AI) or combination with protein 2 (VP2) infectious bursal disease (IBDV) (vHVT-IBD-AI) fusion (F) Newcastle (NDV) (vHVT-ND-AI). In vaccinated chickens, all three vHVT provided 90-100% clinical protection against divergent...
A fully synthetic trivalent mimotope of gp120 conjugated to pan allelic HLA DR binding epitope was prepared using solid-phase peptide synthesis and optimized copper-catalyzed azide−alkyne cycloaddition. The methodology efficiently provides chemically uniform heteromultimeric constructs with enhanced binding, avidity, specificity toward an established HIV-neutralizing human antibody, MAb b12. versatile strategy serves as a powerful platform for the development peptides potential HIV-1 vaccine...
Entry of HIV-1 into target cells requires binding the viral envelope glycoprotein (Env) to cellular receptors and subsequent conformational changes that culminates in fusion cell membranes. Recent structural information has revealed these transitions are regulated by three conserved but potentially flexible layers stacked between receptor-binding domain (gp120) arm (gp41) Env. We hypothesized artificial insertion a covalent bond will 'snap' Env conformation is less mobile stably expose...
The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage emergence vaccine-resistant field underscores need for a broadly protective H5 A vaccine. Here, we tested experimental vector herpesvirus turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived inserts or computationally optimized reactive antigen (COBRA) challenge by homologous genetically divergent HPAI Gs/GD in chickens. Direct...
Methods Here, we designed disulfide-stabilized recombinant HIV1 subtype B (SF162) envelope glycoproteins (Env), gp120 and gp140, by insertion of site-specific cysteine pairs between two layers (layer 1 2) in inner domain gp120. In addition, identified a novel adjuvant approach using Carbopol 971P, cross-linked polyanionic carbomer, combination with the Novartis proprietary oil-in water adjuvant, MF59, to augment humoral immune responses Env glycoprotein. We performed thorough vitro analysis...