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

Assessment of anti-rF1 and anti-rV antibody titres in NHP serum after 3 intramuscular immunizations of 10 μg of rF1 and rV antigen. Detectable amounts of anti-rF1 and anti-rV antibodies were found in the serum 2 weeks after the primary immunization, with anti-rF1 consistently having a higher titre.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4109106&req=5

fig8: Assessment of anti-rF1 and anti-rV antibody titres in NHP serum after 3 intramuscular immunizations of 10 μg of rF1 and rV antigen. Detectable amounts of anti-rF1 and anti-rV antibodies were found in the serum 2 weeks after the primary immunization, with anti-rF1 consistently having a higher titre.

Mentions: To confirm that cynomolgus macaque serum can provide a significant level of protection against pneumonic plague, two cynomolgus macaques were immunised intramuscularly with three 10 μg doses of rF1 and rV vaccine 21 days apart. The antibody titres were monitored and the study terminated after the peak of the anti-rF1 and anti-rV antibody responses. The serum isolated at termination was pooled and the anti-rF1 and anti-rV antibody titres were assessed by ELISA (Figure 8).


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)

Assessment of anti-rF1 and anti-rV antibody titres in NHP serum after 3 intramuscular immunizations of 10 μg of rF1 and rV antigen. Detectable amounts of anti-rF1 and anti-rV antibodies were found in the serum 2 weeks after the primary immunization, with anti-rF1 consistently having a higher titre.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Assessment of anti-rF1 and anti-rV antibody titres in NHP serum after 3 intramuscular immunizations of 10 μg of rF1 and rV antigen. Detectable amounts of anti-rF1 and anti-rV antibodies were found in the serum 2 weeks after the primary immunization, with anti-rF1 consistently having a higher titre.
Mentions: To confirm that cynomolgus macaque serum can provide a significant level of protection against pneumonic plague, two cynomolgus macaques were immunised intramuscularly with three 10 μg doses of rF1 and rV vaccine 21 days apart. The antibody titres were monitored and the study terminated after the peak of the anti-rF1 and anti-rV antibody responses. The serum isolated at termination was pooled and the anti-rF1 and anti-rV antibody titres were assessed by ELISA (Figure 8).

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