Protection conferred by a fully recombinant sub-unit vaccine against Yersinia pestis in male and female mice of four inbred strains

Jones, Steven M.; Day, Fiona H.; Stagg, Anthony J.; Williamson, E. Diane

doi:10.1016/s0264-410x(00)00108-0

Cited by 61 publications

(38 citation statements)

References 22 publications

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“…The dominant subclass was IgG1, with some IgG2 and IgG3 to both antigens, while IgG4 was detectable to rV antigen only. This subclass profile in humans is indicative of a Th2 response, which is the anticipated response to this vaccine since this has also been seen in the mouse (11,30) and nonhuman primates (unpublished data).…”

Section: Discussionmentioning

confidence: 61%

“…The rF1 and rV antigens were produced in Escherichia coli from the expression systems previously described (11), under Good Manufacturing Practice conditions. The vaccine was formulated by adsorption to 20% (vol/vol) alhydrogel (Brenntag Biosector, Frederikssund, Denmark) per ml phosphate-buffered saline (PBS) at the required concentrations of each protein such that concentrations in the range 10 g rF1 ϩ 10 g rV per ml up to 80 g rF1 ϩ 80 g rV per ml were achieved in a final concentration of 0.26% (wt/vol) alhydrogel to achieve a molar ratio for rF1 to rV of 2:1, as previously described (30).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2005

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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 (r 2 ‫؍‬ 98.6%; P < 0.001) and 28 (r 2 ‫؍‬ 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.

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Section: Discussionmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

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

et al. 2005

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“…Other strains of mice tested so far (six inbred strains and Swiss Webster outbred mice) have been found to be highly susceptible to plague, although there are small differences in the LD 50 and mean time to death (3,12). Accordingly, the 129 substrains identified in our study represent a new tool for plague research.…”

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confidence: 71%

Mice Naturally Resistant to Yersinia pestis Δ pgm Strains Commonly Used in Pathogenicity Studies

et al. 2006

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“…93 In contrast, mice do not develop typical buboes, although their lymph nodes are infected and sometimes enlarged. However, the considerable variation in susceptibility to plague among individual rats 94 has made mice the most commonly used model for molecular pathogenesis and vaccine studies since the 1950s. 95 The monkey has also been used as an animal model for plague, 96 Although mammalian animal models are widely accepted for assessment of Y. pestis pathogenesis, an alternative approach using non-mammalian, genetically tractable host organisms is attractive.…”

Section: Models For Y Pestis Pathogenesis Studiesmentioning

confidence: 99%

Current Trends in Plague Research: From Genomics to Virulence

Huang

Nikolich²,

Lindler³

2006

Clinical Medicine & Research

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Yersinia pestis is the causative agent of plague, which diverged from Yersinia pseudotuberculosis within the past 20,000 years. Although these two species share a high degree of homology at the DNA level (>90%), they differ radically in their pathogenicity and transmission. In this review, we briefly outline the known virulence factors that differentiate these two species and emphasize genetic studies that have been conducted comparing Y. pestis and Y. pseudotuberculosis.These comparisons have led to a better understanding of the genetic contributions to the differences in the virulence and pathogenicity between these two organisms and have generated information that can be applied in future diagnostic and vaccine development. Comparison of the genetic differences between Y. pestis and Y. pseudotuberculosis has also lent insight into the emergence of acute pathogens from organisms causing milder diseases.

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Protection conferred by a fully recombinant sub-unit vaccine against Yersinia pestis in male and female mice of four inbred strains

Cited by 61 publications

References 22 publications

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

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

Mice Naturally Resistant to Yersinia pestis Δ pgm Strains Commonly Used in Pathogenicity Studies

Current Trends in Plague Research: From Genomics to Virulence

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