Journal Article

HIV Seroconversion without Infection after Receipt of Adenovirus-Vectored HIV Type 1 Vaccine

Erin K. Quirk, Robin Mogg, Deborah D. Brown, Michelle A. Lally, Devan V. Mehrotra, Mark J. DiNubile and Michael N. Robertson

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 47, issue 12, pages 1593-1599
Published in print December 2008 | ISSN: 1058-4838
Published online December 2008 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/593313
HIV Seroconversion without Infection after Receipt of Adenovirus-Vectored HIV Type 1 Vaccine

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Background. We analyzed human immunodeficiency virus (HIV) seroresponses from 3 phase I HIV-1 vaccine trials to assess the frequency of vaccine-induced seroconversion.

Methods. HIV-1 and HIV-2 enzyme-linked immunosorbent assay (ELISA) was performed during trials of adenovirus type 5 (Ad5)–vectored clade B HIV-1 monovalent gag and trivalent gag/pol/nef vaccines given to HIV-seronegative adults. Doses were administered at day 1, week 4, and week 26. Results were analyzed by vaccine formulation and dose and were stratified by baseline Ad5 titer. ELISA-positive samples were reflexively tested by Western blotting.

Results. Overall, 165 (41%) of 406 evaluable vaccine recipients had positive ELISA results but negative PCR results by week 78. Seroconversion rates were directly related to vaccine dose, were inversely related to baseline Ad5 titer, and were unaffected by vaccine valency. One hundred (89%) of 113 evaluable patients with low baseline Ad5 antibody titers (⩽200) who were given ⩾1 dose of vaccine with ⩾1×1010 gag-containing Ad5 particles per dose experienced seroconversion. Of 163 vaccine recipients who had positive ELISA results and available Western blot results, 150 (92%) had indeterminate results of Western blot, typically involving bands at p24, p40, and/or p55. Thirteen uninfected patients (8%) had equivocally positive Western blot results, usually because of an additional weak glycoprotein 41 band. Env-specific enzyme immunoassay results were falsely positive for 2 uninfected vaccine recipients.

Conclusions. Positive ELISA results were similarly common for monovalent and trivalent vaccine recipients. Vaccine dose and baseline Ad5 immunity were major determinants of vaccine-induced seroconversion rates. Corresponding Western blots characteristically showed bands directed only at Gag proteins, which helped to distinguish HIV-uninfected vaccine recipients who experienced seroconversion from true HIV-infected patients. If available, an enzyme immunoassay exclusively targeting proteins not expressed by the vaccine should be the screening test of first choice for vaccine recipients.

Journal Article.  3743 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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