| Autor: |
Kirkpatrick, Beth D., Tenney, Katherine M., Larsson, Catherine J., O'Neill, J. Patrick, Ventrone, Cassandra, Bentley, Matthew, Upton, Anthony, Hindle, Zoë, Fidler, Christine, Kutzko, Deborah, Holdridge, Regan, Lapointe, Casey, Hamlet, Sandra, Chatfield, Steven N. |
| Předmět: |
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| Zdroj: |
Journal of Infectious Diseases; 8/1/2005, Vol. 192 Issue 3, p360-366, 7p |
| Abstrakt: |
Background. M01ZH09 (Salmonella enterica serovar Typhi [Ty2 aroC- ssaV-] ZH9) is a live oral-dose typhoid vaccine candidate. M01ZH09 was rationally modified with 2 independently attenuating mutations, including a novel mutation in Salmonella pathogenicity island (SPI)-2. We demonstrate that M01ZH09, in a single oral dose, is well tolerated and prompts broad immune responses, regardless of whether prevaccination with a bicarbonate buffer is given. Methods. Thirty-two healthy adult subjects were randomized and given 5 ⊗ 109 cfu of M01ZH09, with (presentation 1) or without (presentation 2) prevaccination with a bicarbonate butter. Immunogenicity data included Salmonella Typhi lipopolysaccharide (LPS)-specific immunoglobulin (Ig) A antibody-secreting cells (enzyme-linked immunospot [ELISPOT] assay), IgG serologic responses to Salmonella Typhi LPS, lymphocyte proliferation, and interferon (IFN)-γ production. Results. The vaccine was well tolerated; adverse events after vaccination were mild. No fever or prolonged vaccine shedding occurred. Immunogenicity data demonstrated that 88% and 93% of subjects who received presentation 1 and presentation 2, respectively, had a positive response by ELISPOT assay; 81% of subjects in both groups underwent IgG seroconversion on day 14. Both groups had similar cellular immune responses to presentation 1 and presentation 2; lymphocyte proliferation to Salmonella Typhi flagellin occurred in 63% and 67% of subjects, respectively, and 69% and 73% of subjects, respectively, had an increase in IFN-γ production. Conclusion. The oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in a single oral dose, with and without prevaccination with a bicarbonate buffer. Field studies to demonstrate protective efficacy are planned. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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