Limits...
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.

Show MeSH

Related in: MedlinePlus

Combined survival plots of 3 studies following passive therapy of mice with either nonimmune or plague vaccinated volunteer serum. Study (1), n = 6 per group, study (2), n = 10 per group, and study (3), n = 10 per group. Mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to more than 10 LD50 aerosolised 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


getmorefigures.php?uid=PMC4109106&req=5

fig2: Combined survival plots of 3 studies following passive therapy of mice with either nonimmune or plague vaccinated volunteer serum. Study (1), n = 6 per group, study (2), n = 10 per group, and study (3), n = 10 per group. Mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to more than 10 LD50 aerosolised Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.

Mentions: A pool of high titre serum obtained from human volunteers that had been vaccinated with experimental recombinant plague vaccine was initially used to assess the concept that passive human antibody therapy would provide some form of protection against pneumonic plague in BALB/c mice. The combined Kaplan-Meier survival curves of three studies are presented in Figure 2. All BALB/c mice were infected three hours after intraperitoneal administration of 250 μL of either nonimmune human serum or a pool of serum from vaccinated volunteers. The serum had a significant protective effect (P < 0.001, Wilcoxon test), as defined by a delay of the median time to death (MTD) of 1 to 2 days (Table 3).


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 3 studies following passive therapy of mice with either nonimmune or plague vaccinated volunteer serum. Study (1), n = 6 per group, study (2), n = 10 per group, and study (3), n = 10 per group. Mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to more than 10 LD50 aerosolised 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

fig2: Combined survival plots of 3 studies following passive therapy of mice with either nonimmune or plague vaccinated volunteer serum. Study (1), n = 6 per group, study (2), n = 10 per group, and study (3), n = 10 per group. Mice were administered 250 μL human serum into the peritoneal cavity, 3 hours before being exposed to more than 10 LD50 aerosolised Y. pestis using a modified contained Henderson apparatus. The median time to death (MTD) was calculated using a Kaplan-Meier survival plot.
Mentions: A pool of high titre serum obtained from human volunteers that had been vaccinated with experimental recombinant plague vaccine was initially used to assess the concept that passive human antibody therapy would provide some form of protection against pneumonic plague in BALB/c mice. The combined Kaplan-Meier survival curves of three studies are presented in Figure 2. All BALB/c mice were infected three hours after intraperitoneal administration of 250 μL of either nonimmune human serum or a pool of serum from vaccinated volunteers. The serum had a significant protective effect (P < 0.001, Wilcoxon test), as defined by a delay of the median time to death (MTD) of 1 to 2 days (Table 3).

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