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Dual route vaccination for plague with emergency use applications
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Journal Article
Dual route vaccination for plague with emergency use applications
2018
Overview
•Induction of rapid immunity (d35); median serum IgG titres to F1 and V of >1800 and >2200 µg/ml respectively.•Induction of specific IgA in serum and faecal extracts.•Full protective efficacy against 2 × 104 median lethal doses of Y. pestis (s.c.) at day 46, 14 days after single boost.•Oral dose effectively boosts systemic immunity and induced mucosal immunity.•VypVaxDuo fulfils rapid response criteria for a vaccine designed for emergency use authorisation.
Here, we report a dual-route vaccination approach for plague, able to induce a rapid response involving systemic and mucosal immunity, whilst also providing ease of use in those resource-poor settings most vulnerable to disease outbreaks. This novel vaccine (VypVaxDuo) comprises the recombinant F1 and V proteins in free association. VypVaxDuo has been designed for administration via a sub-cutaneous priming dose followed by a single oral booster dose and has been demonstrated to induce early onset immunity 14 days after the primary immunisation; full protective efficacy against live organism challenge was achieved in Balb/c mice exposed to 2 × 104 median lethal doses of Yersinia pestis Co92, by the sub-cutaneous route at 25 days after the oral booster immunisation. This dual-route vaccination effectively induced serum IgG and serum and faecal IgA, specific for F1 and V, which constitute two key virulence factors in Y. pestis, and is therefore suitable for further development to prevent bubonic plague and for evaluation in models of pneumonic plague. This is an essential requirement for control of disease outbreaks in areas of the world endemic for plague and is supported further by the observed exceptional stability of the primary vaccine formulation in vialled form under thermostressed conditions (40 °C for 29 weeks, and 40 °C with 75% relative humidity for 6 weeks), meaning no cold chain for storage or distribution is needed.
In clinical use, the injected priming dose would be administered on simple rehydration of the dry powder by means of a dual barrel syringe, with the subsequent single booster dose being provided in an enteric-coated capsule suitable for oral self-administration.
Publisher
Elsevier Ltd,Elsevier Limited
Subject
/ Animals
/ Antibodies, Bacterial - blood
/ Antigens
/ Antigens, Bacterial - immunology
/ Bacterial Proteins - immunology
/ Female
/ Humidity
/ Immunity
/ mice
/ Mucosal
/ Plague
/ Plague - prevention & control
/ Plague Vaccine - administration & dosage
/ Powder
/ Priming
/ Proteins
/ Systemic
/ Vaccine
/ Vaccines
/ Vaccines, Synthetic - administration & dosage
