Performance of a Re-Designed HIV Selectest ELISA Optimized to Minimize Vaccine-Induced Seropositivity in HIV Vaccine Trial Participants.

Publication Type:

Journal Article

Source:

Clinical and vaccine immunology : CVI (2014)

Keywords:

2014, Center-Authored Paper, January 2014, Vaccine and Infectious Disease Division

Abstract:

Vaccine-Induced Seropositivity or Seroreactivity (VISP or VISR), defined as the reaction of antibodies elicited by HIV vaccines with antigens used in HIV diagnostic immunoassays, can result in reactive assay results in vaccinated but uninfected individuals and subsequent misclassification of their infection status. The eventual licensure of a vaccine will magnify this issue and calls for the development of mitigating solutions in advance. An immunoassay that discriminates between antibodies elicited by vaccine antigens and those elicited by infection has been developed to address this laboratory testing need. The HIV Selectest is based on consensus and clade-specific HIV peptides that are omitted in many HIV vaccine constructs. The assay has now been re-designed to enhance performance across worldwide clades and to simplify routine use via a standard kit format. The re-designed assay was evaluated on sera from vaccine trial participants, HIV-infected and uninfected individuals and healthy controls. The HIV Selectest exhibited 99.5% specificity with sera from uninfected recipients of 6 different HIV vaccines and 100% with normal donors, while detecting HIV-1 infected individuals including intercurrent infections at 95-100% sensitivity depending on clade, with highest sensitivity for clades A and C. HIV Selectest sensitivity decreased in very early seroconversion specimens, possibly explaining the slightly lower sensitivity observed in asymptomatic blood donors in comparison with clinical HIV cases. The HIV Selectest thus affords a new laboratory tool for use in vaccine settings to distinguish the immune response to HIV vaccine antigens from that due to true infection.