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Efficacy of primate humoral passive transfer in a murine model of pneumonic plague is mouse strain-dependent.

Graham VA, Hatch GJ, Bewley KR, Steeds K, Lansley A, Bate SR, Funnell SG - J Immunol Res (2014)

Bottom Line: New vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the US Federal Drug Administration's "Animal Rule." This allows licensure of drugs and vaccines using protection data generated in animal models.A new acellular plague vaccine composed of two separate recombinant proteins (rF1 and rV) has been developed and assessed for immunogenicity in humans.Using serum obtained from human volunteers immunised with various doses of this vaccine and from immunised cynomolgus macaques, we assessed the pharmacokinetic properties of human and cynomolgus macaque IgG in BALB/c and the NIH Swiss derived Hsd:NIHS mice, respectively.

View Article: PubMed Central - PubMed

Affiliation: Microbiological Services, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.

ABSTRACT
New vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the US Federal Drug Administration's "Animal Rule." This allows licensure of drugs and vaccines using protection data generated in animal models. A new acellular plague vaccine composed of two separate recombinant proteins (rF1 and rV) has been developed and assessed for immunogenicity in humans. Using serum obtained from human volunteers immunised with various doses of this vaccine and from immunised cynomolgus macaques, we assessed the pharmacokinetic properties of human and cynomolgus macaque IgG in BALB/c and the NIH Swiss derived Hsd:NIHS mice, respectively. Using human and cynomolgus macaque serum with known ELISA antibody titres against both vaccine components, we have shown that passive immunisation of human and nonhuman primate serum provides a reproducible delay in median time to death in mice exposed to a lethal aerosol of plague. In addition, we have shown that Hsd:NIHS mice are a better model for humoral passive transfer studies than BALB/c mice.

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Combined survival plots of mice following passive therapy of either nonimmune or plague vaccinated volunteer serum from 196 to 365 days postinoculation. Study (3), n = 10 per group. BALB/c mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.
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fig4: Combined survival plots of mice following passive therapy of either nonimmune or plague vaccinated volunteer serum from 196 to 365 days postinoculation. Study (3), n = 10 per group. BALB/c mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.

Mentions: The length of the protective effect of immunisation was also tested by comparing the passive protective effect of human vaccine sera taken at 35, 196, and 365 days postimmunisation in the BALB/c pneumonic plague model (Figures 3 and 4). There was no significant difference (P > 0.02, Wilcoxon test) in the passive protection of the mice from the human sera from three different doses and 35, 196, and 365 days postvaccination.


Efficacy of primate humoral passive transfer in a murine model of pneumonic plague is mouse strain-dependent.

Graham VA, Hatch GJ, Bewley KR, Steeds K, Lansley A, Bate SR, Funnell SG - J Immunol Res (2014)

Combined survival plots of mice following passive therapy of either nonimmune or plague vaccinated volunteer serum from 196 to 365 days postinoculation. Study (3), n = 10 per group. BALB/c mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109106&req=5

fig4: Combined survival plots of mice following passive therapy of either nonimmune or plague vaccinated volunteer serum from 196 to 365 days postinoculation. Study (3), n = 10 per group. BALB/c mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.
Mentions: The length of the protective effect of immunisation was also tested by comparing the passive protective effect of human vaccine sera taken at 35, 196, and 365 days postimmunisation in the BALB/c pneumonic plague model (Figures 3 and 4). There was no significant difference (P > 0.02, Wilcoxon test) in the passive protection of the mice from the human sera from three different doses and 35, 196, and 365 days postvaccination.

Bottom Line: New vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the US Federal Drug Administration's "Animal Rule." This allows licensure of drugs and vaccines using protection data generated in animal models.A new acellular plague vaccine composed of two separate recombinant proteins (rF1 and rV) has been developed and assessed for immunogenicity in humans.Using serum obtained from human volunteers immunised with various doses of this vaccine and from immunised cynomolgus macaques, we assessed the pharmacokinetic properties of human and cynomolgus macaque IgG in BALB/c and the NIH Swiss derived Hsd:NIHS mice, respectively.

View Article: PubMed Central - PubMed

Affiliation: Microbiological Services, Public Health England, Porton Down, Salisbury, Wiltshire SP4 0JG, UK.

ABSTRACT
New vaccines against biodefense-related and emerging pathogens are being prepared for licensure using the US Federal Drug Administration's "Animal Rule." This allows licensure of drugs and vaccines using protection data generated in animal models. A new acellular plague vaccine composed of two separate recombinant proteins (rF1 and rV) has been developed and assessed for immunogenicity in humans. Using serum obtained from human volunteers immunised with various doses of this vaccine and from immunised cynomolgus macaques, we assessed the pharmacokinetic properties of human and cynomolgus macaque IgG in BALB/c and the NIH Swiss derived Hsd:NIHS mice, respectively. Using human and cynomolgus macaque serum with known ELISA antibody titres against both vaccine components, we have shown that passive immunisation of human and nonhuman primate serum provides a reproducible delay in median time to death in mice exposed to a lethal aerosol of plague. In addition, we have shown that Hsd:NIHS mice are a better model for humoral passive transfer studies than BALB/c mice.

Show MeSH
Related in: MedlinePlus