Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines.

Abstract

Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271-300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing.

• Authors: Lauriane E Quenee, Nancy A Ciletti, Derek Elli, Timothy M Hermanas, Olaf Schneewind
• Journal: Vaccine (Vaccine) Vol. 29 Issue 38 Pg. 6572-83 (Sep 02 2011) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 21763383 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Bacterial
• Antigens, Bacterial
• Plague Vaccine
• Vaccines, Subunit
• Vaccines, Synthetic
• Aluminum Hydroxide

Topics

• Adjuvants, Immunologic (administration & dosage)
• Aluminum Hydroxide (administration & dosage)
• Animals
• Antibodies, Bacterial (blood)
• Antigens, Bacterial (genetics, immunology)
• Disease Models, Animal
• Guinea Pigs
• Macaca
• Mice
• Mice, Inbred BALB C
• Plague (prevention & control)
• Plague Vaccine (administration & dosage, immunology)
• Primate Diseases (prevention & control)
• Rats
• Rodent Diseases (prevention & control)
• Survival Analysis
• Vaccination (methods)
• Vaccines, Subunit (administration & dosage, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)
• Yersinia pestis (genetics, immunology)