Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children.
BACKGROUND
Despite its high worldwide morbidity and mortality, there is yet no licensed vaccine for shigellosis. We reported the safety and immunogenicity of Shigella O-specific polysaccharide-protein conjugates in adults and young children and efficacy of Shigella sonnei conjugate in young adults.


METHODS
A double-blinded, randomized and vaccine-controlled Phase 3 evaluation of S. sonnei and Shigella flexneri 2a O-SP-rEPA conjugates, 25 microg, injected IM twice, 6 weeks apart, into healthy 1-4 years old, is reported. The children were followed for 2 years by telephone every other week and stool cultures were obtained for each episode of acute diarrhea (> or =3 loose stools/day or a bloody/mucous stool). Sera were taken randomly from 10% of the participants for IgG anti-LPS and anti-carrier levels.


RESULTS
Of the 2799 enrollees, 1433 received S. sonnei and 1366 S. flexneri 2a conjugates; 2699 (96.4%) completed the 2-year follow-up. Local reactions occurred in approximately 5% and approximately 4% had temperatures > or =38.0 degrees C lasting 1-2 days. There were no serious adverse events attributable to the vaccines. Of the 3295 stool cultures obtained, 125 yielded S. sonnei and 21 S. flexneri 2a. Immunogenicity and efficacy were age-related. The overall efficacy of the S. sonnei conjugate was 27.5%; 71.1% (P=0.043) in the 3-4 years old. The numbers for S. flexneri 2a were too few for meaningful analysis. Cross-protection by S. flexneri 2a for non-vaccine S. flexneri types was found, but the numbers were too few for statistical significance. There was an age-related rise of vaccine-specific IgG anti-LPS in both groups, peaking at about 10 weeks and declining thereafter, but remaining > or =4-fold higher than in the controls 2 years after the second dose.


CONCLUSIONS
Shigella conjugates are safe and immunogenic in 1-4 years old. The S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be predicted to be efficacious in individuals older than 3 years of age. These results urge studies with our improved conjugates.
Passwell
Justen H
JH
Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Ashkenazi
Shai
S
Schneider Children's Medical Center, Petach Tikva 49202, Israel.
Banet-Levi
Yonit
Y
Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Ramon-Saraf
Reut
R
Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Farzam
Nahid
N
Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Lerner-Geva
Liat
L
Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer 52621, Israel.
Even-Nir
Hadas
H
Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Yerushalmi
Baruch
B
Saban Pediatric Center, Soroka Medical Center, Beer Sheva 84141, Israel.
Chu
Chiayung
C
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Shiloach
Joseph
J
National Institute of Diabetes, Digestive Diseases and Kidney, NIH, Bethesda, MD 20892, USA.
Robbins
John B
JB
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Schneerson
Rachel
R
Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Electronic address: schneerr@exchange.nih.gov.
D000907:Antibodies, Bacterial / Q000097:blood; D002675:Child, Preschool; D003967:Diarrhea / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D007273:Injections, Intramuscular; D007557:Israel; D008297:Male; D019081:O Antigens / Q000276:immunology*; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology*; D012764:Shigella sonnei / Q000276:immunology*
D000907:Antibodies, Bacterial; D019081:O Antigens; D022281:Shigella Vaccines