Boyd MA, Tennant SM, Saague VA, Simon R, Muhsen K, Ramachandran G, Combination AS, Galen JE, Pasetti MF, Levine MM. for 18 h at 37C, and the zones of motility were measured. Bars: 1, CMF 6999(pLowBlu); 2, CVD 2004(pLowBlu); 3, CVD 2004(pATGclpX); 4, CVD 2005(pLowBlu); 5, CVD 2005(pATGguaBAATGclpX). Data are shown as mean standard deviation (SD). *, test. Download FIG?S1, PDF file, 0.3 MB. Copyright ? 2018 Higginson et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S5. Large-scale BLAST score ratios (LS-BSR) for genes conserved in Paratyphi B (and Java [ 0.8]) but absent in Typhi and Paratyphi A ( 0.4). Download Table?S5, XLSX file, 0.05 MB. Copyright ? 2018 Higginson et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S6. Bacterial strains and plasmids. Download Table?S6, DOCX file, 0.02 MB. Copyright ? 2018 Higginson et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. TABLE?S7. Primers used in this study. Download Table?S7, DOCX file, 0.02 MB. Copyright ? 2018 Higginson et al. This content is distributed under the terms of the Creative Commons Attribution 4.0 International license. ABSTRACT Enteric fever is caused by three serovars: Typhi, Paratyphi A, and Paratyphi B Paratyphi B. To gain genomic insight into these serovars, we sequenced 38 enteric fever-associated strains from Chile and compared these with reference genomes. Each of the serovars was separated genomically based on the core genome. Genomic comparisons identified loci that were aberrant between serovars Paratyphi B and Paratyphi B Java, which is typically associated with gastroenteritis; however, the majority of these were NS 11021 annotated as hypothetical or phage NS 11021 related and thus were Rabbit Polyclonal to GSTT1/4 not ideal vaccine candidates. With the genomic information in hand, we engineered a live attenuated Paratyphi B vaccine strain, CVD 2005, which was capable of protecting mice from both homologous challenge and heterologous challenge with Paratyphi B Java. These findings extend our understanding of Paratyphi B and provide a viable vaccine option for inclusion in a trivalent live attenuated enteric fever vaccine formulation. IMPORTANCE We developed a live attenuated serovar Paratyphi B vaccine that conferred protection in mice against challenge with and NS 11021 Paratyphi B infections is low; however, the development of new conjugate vaccines against other enteric fever serovars could lead to the emergence of Paratyphi B to fill the niche left by these other pathogens. As such, an effective Paratyphi B vaccine would be a useful tool in the armamentarium against infections. Comparative genomics confirmed the serovar-specific groupings of these isolates and revealed that there are a limited number of genetic differences between the and Java strains, which are mostly hypothetical and phage-encoded proteins. The observed level of genomic similarity likely explains why we observe some cross-protection. Paratyphi B disease (7,C9). In a second field NS 11021 trial of Ty21a in Indonesia, where both serovars Typhi and Paratyphi A were circulating, Ty21a protected against typhoid but not against paratyphoid A fever (10). Furthermore, in clinical studies, individuals immunized with Ty21a produced moderate antibody responses that cross-reacted with both Paratyphi B and Paratyphi A (11, 12). Multifunctional CD8+ T cell responses were also elicited in Ty21a-immunized volunteers, which recognized Typhi, and to a lesser extent Paratyphi B, NS 11021 but not Paratyphi A (13). These data suggest that additional or different vaccines are required for adequate protection against paratyphoid fever. There are multiple vaccines in clinical development for [CVD 1902]) and several conjugate vaccines consisting of the Paratyphi A O polysaccharide (OPS) (O:2,12) conjugated to different immunogenic proteins, such as tetanus toxoid, diphtheria toxoid, and CRM197, a nontoxic mutant of diphtheria toxin.
- Therefore, there was no divergent evolution of L-BSE prions about passage through spleen compared to brain
- Abbreviations: NS (not statistically significant); SD (regular deviation)