Recommendations for the Design and Use of Standard Virus Panels To Assess Neutralizing Antibody Responses Elicited by Candidate Human Immunodeficiency Virus Type 1 Vaccines

Abstract

Laboratory measures of antigen-specific immunity are an essential component of the vaccine discovery process. For human immunodeficiency virus type 1 (HIV-1), this process will likely require iterative evaluations of vaccine immunogens to choose the most promising vaccine candidates to advance into human trials. To optimally evaluate and compare vaccine immunogens, we will need high-throughput assays that allow accurate and reproducible measurements of immune responses. In addition, vaccine sponsors and regulatory agencies appropriately require that immune assays associated with human trials be performed in laboratories that comply with guidelines for good laboratory practices (GLP). The rigorous process of assay validation associated with GLP can improve the accuracy of immune assessment assays and contribute to vaccine development by advancing our ability to distinguish incremental improvements in immune responses elicited by novel immunogens. In this commentary, we address several of these issues with regard to the measurement of anti-HIV-1 neutralizing antibodies (NAbs). We recommend the use of DNA plasmids encoding full-length functional HIV-1 envelope glycoproteins (Env); these env clones, when transfected with an HIV-1 envdefective molecular clone, produce well-characterized HIV-1 Env pseudovirions. Additionally, we recommend the establishment of standardized panels of Env-pseudotyped viruses to assess the potencies and breadths of NAbs elicited by vaccine immunogens. These virus panels would form the basis for GLP neutralization assays used to assess sera from clinical vaccine studies, and the same virus panels could be used by investigators interested in the preclinical evaluation of vaccine immunogens.