Development and preclinical evaluation of a trivalent, formalin-inactivated Shigella whole-cell vaccine
| Autor: | Edwin V. Oaks, Richard I. Walker, Kevin R. Turbyfill, August L. Bourgeois, B. Tai, Robert W. Kaminski, M. Wu, L L Van De Verg, Kristen A. Clarkson |
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| Rok vydání: | 2014 |
| Předmět: |
Microbiology (medical)
Male Time Factors Clinical Biochemistry Immunology Guinea Pigs Administration Oral Shigella sonnei medicine.disease_cause Immunoglobulin G Microbiology Shigella flexneri Mice Shigella Vaccines Formaldehyde medicine Immunology and Allergy Animals Shigella Shigella vaccine Lung Mice Inbred BALB C Vaccines biology Immunogenicity Vaccination Temperature biochemical phenomena metabolism and nutrition biology.organism_classification Virology Antibodies Bacterial Immunoglobulin A Intestines Vaccines Inactivated biology.protein bacteria Antibody Disinfectants |
| Zdroj: | Clinical and vaccine immunology : CVI. 21(3) |
| ISSN: | 1556-679X |
| Popis: | Studies were undertaken to manufacture a multivalentShigellainactivated whole-cell vaccine that is safe, effective, and inexpensive. By using several formalin concentrations, temperatures, and incubation periods, an optimized set of inactivation conditions was established forShigella flexneri2a,S. sonnei, andS. flexneri3a to produce inactivated whole cells expressing a full repertoire of Ipa proteins and lipopolysaccharide (LPS). The inactivation conditions selected were treatment with 0.2% formalin (S. flexneri2a and 3a) or 0.6% formalin (S. sonnei) for 48 h at 25°C. Vaccine formulations prepared under different inactivation conditions, in different doses (10E5, 10E7, and 10E9 cells), and with or without the inclusion of double-mutant heat-labile toxin (dmLT) were evaluated in mice. Two intranasal immunizations with ≥10E7 inactivated whole cells resulted in high levels of anti-Invaplex and moderate levels of LPS-specific IgG and IgA in serum and in lung and intestinal wash samples. Addition of dmLT to the vaccine formulations did not significantly enhance humoral immunogenicity. Minimal humoral responses for IpaB, IpaC, or IpaD were detected after immunization with inactivated wholeShigellacells regardless of the vaccine inactivation conditions. In guinea pigs, monovalent formulations ofS. flexneri2a of 3a orS. sonneiconsisting of 10E8, 10E9, or 10E10 cells were protective in a keratoconjunctivitis assay. A trivalent formulation provided protection against all three serotypes (S. flexneri2a,P= 0.018;S. flexneri3a,P= 0.04;S. sonnei,P< 0.0001). The inactivatedShigellawhole-cell vaccine approach incorporates an uncomplicated manufacturing process that is compatible with multivalency and the future development of a broadly protectiveShigellavaccine. |
| Databáze: | OpenAIRE |
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