Relationship Between Virulence and Immunity as Revealed in Recent Studies of the Fl Capsule of Yersinia pestis

Abstract

Yersinia pestis, the causative agent of plague, possesses multiple virulence determinants encoded on its three plasmids and on its chromosome. We evaluated the role of the protein capsule F1 in virulence an immunity against plague. Strains lacking F1, either those that are naturally occurring or those with genetically defined nonpolar mutations in the structural gene, retained their virulence for mice and nonhuman primates. However, both active immunization with F1, from either a recombinant vector or Y. pestis, and passive immunization with F1 monoclonal antibody protected mice from experimental infection with wild-type F1-positive organisms. These results suggest that protective immunogens like F1 need not be essential for virulence. The rare isolation of virulent F1-negative organisms from F1-immunized animals infected with F1-positive strains supports this conclusion and also suggests that, in addition to F1, an optimal vaccine against plague should include essential virulence factors as immunogens.

Plague in Guinea Pigs and Its Prevention by Subunit Vaccines

“…The results suggest that the F1 capsule is not required for the pathogenesis of pneumonic plague in guinea pigs, similar to what has been reported for NHPs and humans. 36,49 The MLD for pneumonic plague in guinea pigs (1000 CFU of Y. pestis CO92) after intranasal instillation is considerably lower than what has been reported for some aerosol challenge experiments. 35 A likely explanation for this observation is the growth condition of cultures, as virulent Y. pestis strains grown at 37°C are more virulent for lung infections in guinea pigs than are the same strains propagated at 26°C.…”

“…27,45 Nonhuman primates are also known to succumb to pneumonic plague after aerosol challenge with F1 mutant strains. 36 We compared the histopathologic findings of pneumonic plague caused by Y. pestis CO92, an F1 ϩ clinical isolate, with that precipitated by its derivative, Y. pestis CAC1 (F1 Ϫ ), a strain that carries an IS1541 insertion in the caf1A structural gene for the outer membrane usher and, therefore, cannot assemble F1 pili. 39 Lung tissues from cynomolgus macaques that died of pneumonic plague after infection with 400 CFUs of either Y. pestis CO92 or CAC1 were stained with H&E ( Figure 1).…”

“…Friedlander and colleagues 36 reported that the MLD for pneumonic plague in guinea pigs was 1 log higher for Y. pestis Java 9 (F1 Ϫ ) than for Y. pestis CO92 (F1 ϩ ). Because the two strains do not represent a pair of wild type and its isogenic F1 variant, the data cannot assess the relative contribution of the F1 capsule to pneumonic plague disease.…”

“…34,35 The mean lethal dose (MLD) and histopathologic attributes of bubonic plague in guinea pigs have, however, not yet been characterized. 34 Furthermore, although previous work demonstrated guinea pig susceptibility to pneumonic plague, 36 the efficacy of subunit vaccines in the guinea pig model system is not yet known. 35 …”

Сapsular Antigen of Yersinia Pestis

“…из печени и селезенки умерщвленных на 1-7-е сутки с момента заражения животных удавалось высевать только F1 + рекомбинант-ные клетки [88]. Рекомбинантные клетки E. coli, способные образовывать капсулу Y. pestis, были устойчивы к фагоцитозу мышиными перитоне-альными макрофагами [59].…”