Recent reports of recovery of broadly cross-neutralizing human monoclonal antibodies (mAbs) from infected individuals with bNab responses have greatly enhanced understanding of epitopes that induce such responses –. ![]() ![]() Furthermore, vaccine approaches that emphasize induction of cellular immunity have not generally resulted in complete protection from infection in non-human primate models, and in one clinical trial vaccinated individuals were more likely to become infected than controls. The need for such responses is highlighted by results of clinical trials of HIV-1 Env-based vaccine candidates that induced weak nAb with little cross reactivity and that resulted in either no protection or short term protection of the minority of vaccinees in the trial. Efforts to induce potent, broadly cross-reactive HIV-1 neutralizing antibodies (bNab) have included many approaches, none of which have been highly successful. The reasons for difficulty in achieving this goal are numerous, and include extreme genetic variability of the Env genes and the ability of the virus to shield critical epitopes through various structural mechanisms. Induction of antibodies that neutralize many strains of human immunodeficiency virus type 1 (HIV-1) cross-reactively is a major goal of HIV-1 vaccine development efforts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. All data are included within the manuscript.įunding: Funded by National Institutes of Health Grant AI078412 website. The work is made available under the Creative Commons CC0 public domain dedication.ĭata Availability: The authors confirm that all data underlying the findings are fully available without restriction. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: ApAccepted: ApPublished: May 20, 2014 Dimitrov, CIP, NCI-Frederick, NIH, United States of America (2014) Immunization of Rabbits with Highly Purified, Soluble, Trimeric Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces a Vigorous B Cell Response and Broadly Cross-Reactive Neutralization. The results demonstrate that highly purified gp140-GCN4-L trimer in adjuvant elicits BCN responses in rabbits accompanied by vigorous B cell induction.Ĭitation: Quinnan GV Jr, Onabajo O, Zhang P, Yan L, Mattapallil JJ, Zhang Z, et al. Induction of spleen B cell and plasma cells producing immunoglobulins that bound trimeric gp140-GCN4-L was vigorous, based on ELISpot and flow cytometry analyses. The specificity of these responses did not appear similar to that of any of the known BCN human mAbs. Rabbits that were given a seventh dose of gp140-GCN4-L developed BCN responses that were weak to moderate, similar to our previous report. Weak neutralization of some strains of HIV-1 was seen after two additional doses in AS02 A. All Envs bound CD4i mAbs in the presence and absence of sCD4, as reported for the R2 Env. The different forms of gp140 bound broadly cross-reactive neutralizing (BCN) human monoclonal antibodies (mAbs) similarly in ELISA and immunoprecipitation assays. Multimeric states of the Env proteins were assessed by native gel electrophoresis and analytical ultracentrifugation. The forms of this Env that were produced in and purified from stably transformed 293T cells included a primarily dimeric gp140, a trimeric gp140 appended to a GCN4 trimerization domain (gp140-GCN4), gp140-GCN4 with a 15 amino acid flexible linker between the gp120 and gp41 ectodomain (gp140-GCN4-L), also trimeric, and a gp140 with the flexible linker purified from cell culture supernatants as either dimer (gp140-L(D)) or monomer (gp140-L(M)). Here, we compared different forms of the same HIV-1 strain R2 Env for antigenic and biophysical characteristics, and in rabbits characterized the extent of B cell induction for specific antibody expression and secretion and neutralizing responses. Previously we described induction of cross-reactive HIV-1 neutralizing antibody responses in rabbits using a soluble HIV-1 gp140 envelope glycoprotein (Env) in an adjuvant containing monophosphoryl lipid A (MPL) and QS21 (AS02 A).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |