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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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Related in: MedlinePlus

Pharmacokinetics of human or cynomolgus macaque antibody in BALB/c and Hsd:NIHS mice, respectively. 0.25 mL human ((a) and (c)) or cynomolgus macaque ((b) and (d)) plague vaccine serum was injected via the intraperitoneal route into BALB/c (n = 20) or Hsd:NIHS (n = 20) mice, respectively. The mice were serially sacrificed and the presence of anti-rF1 ((a) and (b)) or anti-rV ((c) and (d)) antibody was assessed by ELISA. Additional groups of mice (n = 5) were sacrificed preinjection to provide baseline data. The data suggests that the time delay between passive antibody administration and optimal serum concentration in the murine serum was between 3 and 6 hours. a.u., arbitrary units.
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fig1: Pharmacokinetics of human or cynomolgus macaque antibody in BALB/c and Hsd:NIHS mice, respectively. 0.25 mL human ((a) and (c)) or cynomolgus macaque ((b) and (d)) plague vaccine serum was injected via the intraperitoneal route into BALB/c (n = 20) or Hsd:NIHS (n = 20) mice, respectively. The mice were serially sacrificed and the presence of anti-rF1 ((a) and (b)) or anti-rV ((c) and (d)) antibody was assessed by ELISA. Additional groups of mice (n = 5) were sacrificed preinjection to provide baseline data. The data suggests that the time delay between passive antibody administration and optimal serum concentration in the murine serum was between 3 and 6 hours. a.u., arbitrary units.

Mentions: To maximise the efficacy of passively transferred antibodies, we examined the pharmacokinetics of human antibody in the circulating blood stream of BALB/c mice (Figure 1). The results indicated that optimal human antibody concentrations were reached between three and six hours after intraperitoneal administration into 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)

Pharmacokinetics of human or cynomolgus macaque antibody in BALB/c and Hsd:NIHS mice, respectively. 0.25 mL human ((a) and (c)) or cynomolgus macaque ((b) and (d)) plague vaccine serum was injected via the intraperitoneal route into BALB/c (n = 20) or Hsd:NIHS (n = 20) mice, respectively. The mice were serially sacrificed and the presence of anti-rF1 ((a) and (b)) or anti-rV ((c) and (d)) antibody was assessed by ELISA. Additional groups of mice (n = 5) were sacrificed preinjection to provide baseline data. The data suggests that the time delay between passive antibody administration and optimal serum concentration in the murine serum was between 3 and 6 hours. a.u., arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Pharmacokinetics of human or cynomolgus macaque antibody in BALB/c and Hsd:NIHS mice, respectively. 0.25 mL human ((a) and (c)) or cynomolgus macaque ((b) and (d)) plague vaccine serum was injected via the intraperitoneal route into BALB/c (n = 20) or Hsd:NIHS (n = 20) mice, respectively. The mice were serially sacrificed and the presence of anti-rF1 ((a) and (b)) or anti-rV ((c) and (d)) antibody was assessed by ELISA. Additional groups of mice (n = 5) were sacrificed preinjection to provide baseline data. The data suggests that the time delay between passive antibody administration and optimal serum concentration in the murine serum was between 3 and 6 hours. a.u., arbitrary units.
Mentions: To maximise the efficacy of passively transferred antibodies, we examined the pharmacokinetics of human antibody in the circulating blood stream of BALB/c mice (Figure 1). The results indicated that optimal human antibody concentrations were reached between three and six hours after intraperitoneal administration into 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