A single dose sub-unit vaccine protects against pneumonic plague

In this study, the protection afforded against aerosolised Yersinia pestis by injection of a single dose of an alhydrogel-adsorbed sub-unit vaccine ha s been compared with that given by an existing killed whole cell vaccine li censed for human use. The sub-unit vaccine, prepared by admiring F1 antigen derived from a I: pestis cell culture supernatant with recombinant V antig en derived from an E. coli cell lysate, fully protected an outbred strain o f mouse against exposure to 10(6) CFU of virulent plague organisms (10(4) m ouse lethal doses, MLD). In contrast, the whole cell vaccine provided only 16% protection against the same level of challenge. Furthermore, sub-unit v accinees were able to clear the bacteria from their lungs post-challenge wh ereas bacteria were cultured from the lungs of a surviving KWC vaccinee pos t-challenge. In killed whole cell vaccinees, physiologically significant le vels of IgG to F1 only were detectable and the levels of F1-specific IgG in serum and in broncho-alveolar washings were significantly lower (p < 0.05) compared with sub-unit vaccinees. In sub-unit vaccinees, an IgG titre to t he F1 and V antigens was detected in serum where it was significantly highe r (p < 0.05) compared with broncho-alveolar washings suggesting that, at th e time of challenge, protection is attributable mainly to the combined circ ulating IgG titre to the F1 and V sub-units. The enhanced protective effica cy of this sub-unit vaccine administered as a single dose compared with an existing vaccine has been demonstrated in an outbred animal model of pneumo nic plague. (C) 2000 Elsevier Science Ltd. All rights reserved.