Scientific Publications by FDA Staff
Clin Vaccine Immunol 2010 Aug;17(8):1244-51
Characterization of immune responses to capsid protein p24 of human immunodeficiency virus type 1 and implications for detection.
Tang S, Zhao J, Wang A, Viswanath R, Harma H, Little RF, Yarchoan R, Stramer SL, Nyambi PN, Lee S, Wood O, Wong EY, Wang X, Hewlett IK
To further refine our current nanoparticle-based HIV-1 p24 antigen assay, we investigated immune responses to p24 to identify diagnostically significant immune dominant epitopes (IDEs) in HIV infected human sera, to address cross-reactivity of anti-p24 antibodies to different subtypes, and to identify new biomarkers that distinguish acute from chronic HIV infection for more accurate incidence estimation. We identified two major linear epitope regions located in the CypA binding loop and adjacent helices and at the end of the C-terminal domain. Most sera (86%) from acutely HIV-1 infected individuals reacted with multiple peptides while 60% and 30% of AIDS patient samples reacted with multiple or single peptides, respectively. In contrast, 46% and 43% of chronically HIV-1 infected individuals reacted with either one or none of the peptides, respectively, and only 11% reacted with multiple p24 peptides indicating a progression of immune responses from polyclone-like during acute infection to monoclone-like or non-response to linear epitopes during chronic infection. Anti-p24 antibodies (subtype B) show broad cross-reactivity with different HIV-1 subtypes and the synergistic action of different combinations of anti-HIV antibodies improves capture and detection of divergent HIV-1 subtypes. Our results indicate that the modified peptide immunoassay was sensitive and specific for the rapid identification of HIV-1 p24 IDEs, and for investigation of immune responses to p24 during natural HIV-1 infection. The data provide the foundation for development and refinement of new assays for improved p24 antigen testing as future tools for rapid and accurate diagnosis as part of early intervention strategies and estimation of incidence.
|Category: Journal Article|
|PubMed ID: #20534793||DOI: 10.1128/CVI.00066-10|
|PubMed Central ID: #PMC2916249|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|