Track topics on Twitter Track topics that are important to you
Eliciting broadly neutralizing antibodies (bnAbs) targeting envelope (Env) is a major goal of HIV vaccine development, but cross-clade breadth from immunization has only sporadically been observed. Recently, Xu et al (2018) elicited cross-reactive neutralizing antibody responses in a variety of animal models using immunogens based on the epitope of bnAb VRC34.01. The VRC34.01 antibody, which was elicited by natural human infection, targets the N terminus of the Env fusion peptide, a critical component of the virus entry machinery. Here we precisely characterize the functional epitopes of VRC34.01 and two vaccine-elicited murine antibodies by mapping all single amino-acid mutations to the BG505 Env that affect viral neutralization. While escape from VRC34.01 occurred via mutations in both fusion peptide and distal interacting sites of the Env trimer, escape from the vaccine-elicited antibodies was mediated predominantly by mutations in the fusion peptide. Cryo-electron microscopy of four vaccine-elicited antibodies in complex with Env trimer revealed focused recognition of the fusion peptide and provided a structural basis for development of neutralization breadth. Together, these functional and structural data suggest that the breadth of vaccine-elicited antibodies targeting the fusion peptide can be enhanced by specific interactions with additional portions of Env. Thus, our complete maps of viral escape both delineate pathways of resistance to these fusion peptide-directed antibodies and provide a strategy to improve the breadth or potency of future vaccine-induced antibodies against Env's fusion peptide.
This article was published in the following journal.
Name: PLoS pathogens
Chlamydia trachomatis (Ct), the most common bacterial STI, leads to pelvic inflammatory disease, infertility, and ectopic pregnancy in women. In this Perspective, we discuss the successful human papil...
It is widely accepted that live vaccines elicit higher immune protection than inactivated vaccines. However, the mechanisms are largely unknown. Here, an array with 64 recombinant outer membrane prote...
Characterization of the epitopes on antigen recognized by monoclonal antibodies (mAb) is useful for the development of therapeutic antibodies, diagnostic tools, and vaccines. Epitope mapping also prov...
While the cellular immune response associated with acute and chronic HBV infection has been thoroughly studied, the B cell response in chronic hepatitis B and the role of antibodies raised against the...
Development of broadly reactive or universal influenza vaccines will be a paradigm shifting event for the influenza vaccine field. These next generation vaccines could replace the current standard of ...
The aims of this study are: 1. to investigate if HIV infection alters the antibody responses to influenza and 2. to assess the ability of licensed influenza vaccine to induce functio...
Varicella is a vaccine-preventable disease, which can be severe in immunosuppressed children. Currently, the (live) vaccine is not recommended in pediatric orthotopic liver transplant reci...
The aim of the study is to assess the safety of the primary series vaccine schedules and the booster vaccination Primary Objectives: - To demonstrate the non-inferiority of the ...
The purpose of this study is to see if an investigational vaccine can make antibodies (proteins found in blood) in humans that will influence the course of an AIDS-like disease in monkeys....
In natural HIV disease, a small fraction (1-2%) of infected individuals develops exceptionally high titres of HIV-1 neutralizing serum activity. Antibodies isolated from these individuals ...
Antibodies elicited in a different species from which the antigen originated. These antibodies are directed against a wide variety of interspecies-specific antigens, the best known of which are Forssman, Hanganutziu-Deicher (H-D), and Paul-Bunnell (P-B). Incidence of antibodies to these antigens--i.e., the phenomenon of heterophile antibody response--is useful in the serodiagnosis, pathogenesis, and prognosis of infection and latent infectious states as well as in cancer classification.
The relationship between an elicited ADAPTIVE IMMUNE RESPONSE and the dose of the vaccine administered.
A combined vaccine used to prevent infection with diphtheria and tetanus toxoid. This is used in place of DTP vaccine (DIPHTHERIA-TETANUS-PERTUSSIS VACCINE) when PERTUSSIS VACCINE is contraindicated.
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)
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.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...