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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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Mouse strain BALB/c and Hsd:NIHS had similar susceptibly to aerosolised Y. pestis. (a) shows the survival plots for Hsd:NIHS and (b) shows the survival plots for BALB/c mice. Study (4), n = 5 per group. The MTD was calculated using a Kaplan-Meier survival plot.
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fig6: Mouse strain BALB/c and Hsd:NIHS had similar susceptibly to aerosolised Y. pestis. (a) shows the survival plots for Hsd:NIHS and (b) shows the survival plots for BALB/c mice. Study (4), n = 5 per group. The MTD was calculated using a Kaplan-Meier survival plot.

Mentions: An aerosol model of murine plague using Hsd:NIHS mice was developed to enable assessment of the efficacy of passive transfer of human antibodies. Results showed that there was no difference in the time to death of Hsd:NIHS mice (P > 0.02, Mann-Whitney) compared to BALB/c mice after aerosol challenge of Y. pestis (Figure 6), and Table 3 demonstrates that a presented dose of 2.4 LD50 or above results in an average MTD of 5.3 days (±0.8 SE).


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)

Mouse strain BALB/c and Hsd:NIHS had similar susceptibly to aerosolised Y. pestis. (a) shows the survival plots for Hsd:NIHS and (b) shows the survival plots for BALB/c mice. Study (4), n = 5 per group. 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

fig6: Mouse strain BALB/c and Hsd:NIHS had similar susceptibly to aerosolised Y. pestis. (a) shows the survival plots for Hsd:NIHS and (b) shows the survival plots for BALB/c mice. Study (4), n = 5 per group. The MTD was calculated using a Kaplan-Meier survival plot.
Mentions: An aerosol model of murine plague using Hsd:NIHS mice was developed to enable assessment of the efficacy of passive transfer of human antibodies. Results showed that there was no difference in the time to death of Hsd:NIHS mice (P > 0.02, Mann-Whitney) compared to BALB/c mice after aerosol challenge of Y. pestis (Figure 6), and Table 3 demonstrates that a presented dose of 2.4 LD50 or above results in an average MTD of 5.3 days (±0.8 SE).

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