Selection and Analysis of HIV-1 Envelope Epitopes for Design of Vaccines that can Induce Broadly Neutralizing Antibodies

Aladin Research Commons

Selection and Analysis of HIV-1 Envelope Epitopes for Design of Vaccines that can Induce Broadly Neutralizing Antibodies

Show simple item record

dc.contributor.advisor Rao, Venigalla B en_US Wieczorek, Lindsay Marie en_US
dc.contributor.other Golin, John E en_US
dc.contributor.other Greene, James J en_US 2012-06-01T16:44:38Z 2012-06-01T16:44:38Z 2012 en_US 2012-06-01
dc.identifier.other Wieczorek_cua_0043A_10298 en_US
dc.description Degree awarded: Ph.D. Biology. The Catholic University of America en_US
dc.description.abstract HIV-1 vaccines are designed to mimic the structure and contextual elements of viral epitopes that have the potential to induce broadly neutralizing antibodies (bnAbs) <italic>in vivo</italic>. The structure of gp41 membrane proximal external region (MPER), targeted by three bnAbs, is poorly defined. The goal of this study is to select epitopes with enhanced binding to MPER bnAbs, to identify neutralization-competent structures by characterizing the function of epitope-specific antibodies <italic>in vivo</italic> and to determine if these selected MPER epitopes can be used to broaden the immune response as potential vaccines.MPER epitopes were selected by biopanning with phage-displayed peptide libraries against bnAbs 4E10, 2F5 and Z13. Epitopes were screened in antigen competition binding assays where M13-displayed epitopes competed with HIV-1 envelope peptides or infectious HIV-1 particles for antibody binding. <italic>In vivo</italic> response to MPER was assessed by M13 immunoprecipitation and neutralization competition assays using HIV-positive plasma. Immunogenicity of select epitopes was determined by immunization of mice and elicited cellular and humoral immune responses were assessed.Unique 4E10, and known 2F5 and Z13, epitopes were selected from M13 phage display libraries, which were able to compete with envelope peptide and HIV-1 for antibody binding. 4E10 and 2F5 epitopes were found to be immunogenic during HIV-1 infection; of the twelve HIV+ patient plasma tested, 100% and 58% reacted with phage-displayed 4E10 and 2F5 MPER epitopes, respectively. 4E10-epitopes were capable of absorbing MPER-specific neutralizing antibodies in HIV+ plasma. Mouse immunization with selected, neutralization-competent MPER epitopes elicited HIV-1 specific cellular and humoral immune responses and boosted the neutralizing activity of a gp145 protein subunit vaccine.Unique 4E10 epitopes, that represent functional HIV-1 envelope trimers, were identified. Chronically HIV-infected individuals generate neutralizing antibodies to a subset of the selected MPER-variant epitopes. These M13-displayed 4E10 epitopes have the potential to elicit HIV-1 neutralizing antibodies in mice. Increasing the range of antibody recognition to MPER, potentially by vaccination with multiple MPER variant epitopes, will be the key to improve HIV-1 vaccine design. en_US
dc.format.extent 102 p. en_US
dc.format.mimetype application/pdf en_US
dc.publisher The Catholic University of America en_US
dc.subject Microbiology en_US
dc.subject Virology en_US
dc.subject Immunology en_US
dc.subject.other 4E10 en_US
dc.subject.other antibody en_US
dc.subject.other envelope en_US
dc.subject.other HIV en_US
dc.subject.other membrane proximal external region en_US
dc.subject.other vaccine en_US
dc.title Selection and Analysis of HIV-1 Envelope Epitopes for Design of Vaccines that can Induce Broadly Neutralizing Antibodies en_US
dc.type Text en_US
dc.type Dissertation en_US

Files in this item

Files Size Format View
Wieczorek_cua_0043A_10298display.pdf 10.25Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account