Nature Medicine
- 12, 1310 - 1315 (2006)
Published online: 5 November 2006; | doi:10.1038/nm1457
Quantification of antibody responses against multiple antigens of the two infectious forms of Vaccinia virus provides a benchmark for smallpox vaccinationMike M Pütz1, 3, Claire M Midgley1, 3, Mansun Law2 & Geoffrey L Smith11
Department of Virology, Faculty of Medicine, Imperial College London, St. Mary's Campus, London W2 1PG, UK. 2
Present address: Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. 3
These authors contributed equally to this work.
Correspondence should be addressed to Geoffrey L Smith glsmith@imperial.ac.uk Smallpox was eradicated without an adequate understanding of how vaccination induced protection. In response to possible bioterrorism with smallpox, the UK government vaccinated  300 health care workers with vaccinia virus (VACV) strain Lister. Antibody responses were analyzed using ELISA for multiple surface antigens of the extracellular enveloped virus (EEV) and the intracellular mature virus (IMV), plaque reduction neutralization and a fluorescence-based flow cytometric neutralization assay. Antibody depletion experiments showed that the EEV surface protein B5 is the only target responsible for EEV neutralization in vaccinated humans, whereas multiple IMV surface proteins, including A27 and H3, are targets for IMV-neutralizing antibodies. These data suggest that it would be unwise to exclude the B5 protein from a future smallpox vaccine. Repeated vaccination provided significantly higher B5-specific and thus EEV-neutralizing antibody responses. These data provide a benchmark against which new, safer smallpox vaccines and residual immunity can be compared.
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