Human immunodeficiency virus (HIV) vaccine trials: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies.
All current human immunodeficiency virus (HIV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates >99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within 1 to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide.
Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Bethesda, MD 20892, USA.
Surender
S
Khurana
James
J
Needham
Bonnie
B
Mathieson
Isaac R
IR
Rodriguez-Chavez
Andrew T
AT
Catanzaro
Robert T
RT
Bailer
Jerome
J
Kim
Vicky
V
Polonis
David A
DA
Cooper
Jan
J
Guerin
Michael L
ML
Peterson
Marc
M
Gurwith
Nga
N
Nguyen
Barney S
BS
Graham
Hana
H
Golding
D016915:AIDS Vaccines / Q000276:immunology*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005189:False Positive Reactions; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology; D006679:HIV Seropositivity; D006801:Humans; D019151:Peptide Library; D012680:Sensitivity and Specificity
D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D019151:Peptide Library