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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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Passive immune therapy with NHP serum provided better protection in Hsd:NIHS mice than human serum after a lethal challenge of Y. pestis. Study (6), n = 10 mice per group. Mice were administered 250 μL serum into the peritoneal cavity, 3–6 hours before being exposed to aerosolised Y. pestis using a modified contained Henderson apparatus. The MTD was calculated using a Kaplan-Meier survival plot.
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fig9: Passive immune therapy with NHP serum provided better protection in Hsd:NIHS mice than human serum after a lethal challenge of Y. pestis. Study (6), n = 10 mice per group. Mice were administered 250 μL serum into the peritoneal cavity, 3–6 hours before being exposed to aerosolised Y. pestis using a modified contained Henderson apparatus. The MTD was calculated using a Kaplan-Meier survival plot.

Mentions: The cynomolgus macaque serum was used in an assessment of passive protection in Hsd:NIHS mice against an aerosolised challenge of Y. pestis. The MTD of the untreated mice was observed to be 3.5 days, whereas the MTD of mice treated with the highest titre of human serum was 7.7 days (Figure 9). The MTD for the mice treated with the cynomolgus macaque serum could not be determined because 60% of the mice survived until day 14. However, there was no statistical difference (P > 0.02, Wilcoxon) between the passive protective effect of human and cynomolgus macaque vaccine sera in Hsd:NIHS mice.


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)

Passive immune therapy with NHP serum provided better protection in Hsd:NIHS mice than human serum after a lethal challenge of Y. pestis. Study (6), n = 10 mice per group. Mice were administered 250 μL serum into the peritoneal cavity, 3–6 hours before being exposed to aerosolised Y. pestis using a modified contained Henderson apparatus. The 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

fig9: Passive immune therapy with NHP serum provided better protection in Hsd:NIHS mice than human serum after a lethal challenge of Y. pestis. Study (6), n = 10 mice per group. Mice were administered 250 μL serum into the peritoneal cavity, 3–6 hours before being exposed to aerosolised Y. pestis using a modified contained Henderson apparatus. The MTD was calculated using a Kaplan-Meier survival plot.
Mentions: The cynomolgus macaque serum was used in an assessment of passive protection in Hsd:NIHS mice against an aerosolised challenge of Y. pestis. The MTD of the untreated mice was observed to be 3.5 days, whereas the MTD of mice treated with the highest titre of human serum was 7.7 days (Figure 9). The MTD for the mice treated with the cynomolgus macaque serum could not be determined because 60% of the mice survived until day 14. However, there was no statistical difference (P > 0.02, Wilcoxon) between the passive protective effect of human and cynomolgus macaque vaccine sera in Hsd:NIHS mice.

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