The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations.
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 5x109 cfu of M01ZH09, with (presentation 1) or without (presentation 2) prevaccination with a bicarbonate buffer. 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)- gamma 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- gamma production.


CONCLUSIONS
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.
Kirkpatrick
Beth D
BD
Department of Medicine, Unit of Infectious Diseases, University of Vermont College of Medicine, Burlington, 05405, USA. beth.kirkpatrick@uvm.edu.
Tenney
Katherine M
KM
Larsson
Catherine J
CJ
O'Neill
J Patrick
JP
Ventrone
Cassandra
C
Bentley
Matthew
M
Upton
Anthony
A
Hindle
Zoe
Z
Fidler
Christine
C
Kutzko
Deborah
D
Holdridge
Regan
R
Lapointe
Casey
C
Hamlet
Sandra
S
Chatfield
Steven N
SN
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005612:Freeze Drying; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019779:Salmonella enterica / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000633:toxicity; D014613:Vaccines, Attenuated
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; C503988:typhoid vaccine M01ZH09