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Infection and Immunity, June 2005, p. 3598-3608, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3598-3608.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Immune Response to a Plague Vaccine Comprising Recombinant F1 and V Antigens

E. D. Williamson,* H. C. Flick-Smith, C. LeButt, C. A. Rowland, S. M. Jones,{dagger} E. L. Waters, R. J. Gwyther, J. Miller, P. J. Packer, and M. Irving

Dstl Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom

Received 15 December 2004/ Returned for modification 7 January 2005/ Accepted 28 January 2005

The human immune response to a new recombinant plague vaccine, comprising recombinant F1 (rF1) and rV antigens, has been assessed during a phase 1 safety and immunogenicity trial in healthy volunteers. All the subjects produced specific immunoglobulin G (IgG) in serum after the priming dose, which peaked in value after the booster dose (day 21), with the exception of one individual in the lowest dose level group, who responded to rF1 only. Three subjects, found to have an anti-rV titer at screening, were excluded from the overall analysis. Human antibody functionality has been assessed by quantification of antibody competing for binding to rV in vitro and also by the transfer of protective immunity in human serum into the naïve mouse. Human and macaque IgG competed for binding to rV in vitro with a mouse monoclonal antibody, previously shown to protect mice against challenge with plague, suggesting that this protective B-cell epitope on rV is conserved between these three species. Total IgG to rV in individuals and the titer of IgG competing for binding to rV correlated significantly at days 21 (r = 0.72; P < 0.001) and 28 (r = 0.82; P < 0.001). Passive transfer of protective immunity into mice also correlated significantly with total IgG titer to rF1 plus rV at days 21 (r2 = 98.6%; P < 0.001) and 28 (r2 = 76.8%; P < 0.03). However, no significant vaccination-related change in activation of peripheral blood mononuclear cells was detected at any time. Potential serological immune correlates of protection have been investigated, but no trends specific to vaccination could be detected in cellular markers.

* Corresponding author. Mailing address: Dstl Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom. Phone: 44 1980 613985. Fax: 44 1980 613985. E-mail: dwilliamson{at}dstl.gov.uk.

Editor: D. L. Burns

{dagger} Present address: Special Pathogens Program, National Microbiology Laboratory, Canadian Science Centre for Human and Animal Health, Winnipeg, Manitoba, Canada R3E 3R2.

Infection and Immunity, June 2005, p. 3598-3608, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3598-3608.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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