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Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design.
This article was published in the following journal.
Name: Cell reports
The N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing the structural flexibili...
During the entry process, the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagem...
Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand t...
Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being e...
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To determine the reactivity and safety of HIV-1 recombinant envelope glycoprotein gp160. To determine the immunogenicity of gp160. Although recent advances have been made in antiviral the...
To determine the safety of vaccinia-derived HIV-1 recombinant envelope glycoprotein (gp160) in human volunteers; to evaluate the immunogenicity of this preparation in human volunteers. Alt...
A Phase I Multicenter Clinical Trial to Evaluate the Safety and Immunogenicity of Vaccinia Derived HIV-1 Recombinant Envelope Glycoprotein (gp160) of Human Immunodeficiency Virus: Evaluation of Accelerated Schedules
To evaluate the safety and immune response to vaccinia-derived HIV-1 recombinant envelope glycoprotein (gp160) using an accelerated dosage schedule; to evaluate duration of antibody respon...
A Phase I Multicenter Clinical Trial to Evaluate the Safety and Immunogenicity of Vaccinia Derived HIV-1 Recombinant Envelope Glycoprotein (gp160) of Human Immunodeficiency Virus: Evaluation of a 200-Mcg Dose
To determine the safety of and immune response to vaccinia-derived HIV-1 recombinant envelope glycoprotein (gp160) at a dose of 200 mcg in human volunteers; to evaluate duration of antibod...
To evaluate the safety and immune response to 160 mcg HIV-1 recombinant envelope glycoprotein gp160. To evaluate the duration of antibody response and its relationship to dose and frequenc...
Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.
An envelope protein of the human immunodeficiency virus that is encoded by the HIV env gene. It has a molecular weight of 160,000 kDa and contains numerous glycosylation sites. It serves as a precursor for both the HIV ENVELOPE PROTEIN GP120 and the HIV ENVELOPE PROTEIN GP41.
Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.
Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus.
The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.
Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...