TY - JOUR
T1 - Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age
AU - Qadri, Firdausi
AU - Ahmed, Tanvir
AU - Ahmed, Firoz
AU - Sack, R. Bradley
AU - Sack, David A.
AU - Svennerholm, Ann Mari
AU - Begum, Yasmin Ara
AU - Akter, Nargis
AU - Akhter, Khuzista
AU - Begum, Perveen
AU - Begum, Razia
AU - Rahman, Taufiqur
AU - Dutta, Khokon Kumar
AU - Hossain, Delowar
AU - Das, Prodip Chandra
AU - Rahman, Lutfur
N1 - Funding Information:
This study was conducted at the ICDDR, B: Centre for Health and Population Research with the support of grants from the USAID (Grant No. HRN-A-00-96-90005-00) and the Swedish Agency for Research and Economic Cooperation (SAREC-1995-0069) and the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B): Centre for Health and Population Research. The Centre is supported by agencies and countries which share its concern for the health problems of developing countries. Ms. Gudrun Wilkund is gratefully acknowledged for purifying the different CFs used in the study. We thank the members of the Safety Monitoring Committee formulated for the project (Drs. M.A. Salam, Rashidul Haque, ASG Faruque and K. Zaman for their review and support in the study.
PY - 2003/6/2
Y1 - 2003/6/2
N2 - A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 mosnths of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P≤0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P≤0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.
AB - A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli (ETEC) vaccine containing six colonization factors (CFA/I, CS1, CS2, CS3, CS4, CS5) and 1mg of recombinant cholera toxin B subunit (the CF-BS-ETEC vaccine) was carried out in an urban slum of Dhaka city in Bangladesh. The study was carried out in a double blinded, placebo controlled design in 158 children, 18-36 mosnths of age. Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12. The vaccine was well tolerated. The immune response was studied in 60 children (30 each in the placebo and vaccine group). Significant vaccine specific IgA antibody-secreting cell (ASC) responses were seen 7 days after ingestion of the first and second dose of the vaccine. The responses to CFA/I (P≤0.001), CS2 (P=0.021), CS4 (P=0.009) and rCTB (P≤0.001) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients (P=0.018 to <0.001). Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested (P=0.012 to <0.001) and IgG-ASCs to rCTB (P<0.001). Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose. The vaccine recipients also responded with IgA plasma antibodies to CFA/I, CS1, CS2, CS4 and rCTB after one or two doses of the vaccine (P=0.01 to <0.001). Subjects in the placebo group failed to mount responses to any of the antigens. The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I, CS2 and rCTB (61, 88 and 69% responder frequency, respectively) and the magnitude of the response was elevated in comparison to the pre-immune levels (P=0.031 to <0.001) and to the levels of the control group (P=0.003 to <0.001). This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children, 18-36 months of age and gives rise to significant systemic and mucosal IgA antibody responses.
KW - Children
KW - Enterotoxigenic Escherichia coli (ETEC) vaccine
KW - Immunogenicity
KW - Safety
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U2 - 10.1016/S0264-410X(03)00077-X
DO - 10.1016/S0264-410X(03)00077-X
M3 - Article
C2 - 12744870
AN - SCOPUS:12444254793
SN - 0264-410X
VL - 21
SP - 2394
EP - 2403
JO - Vaccine
JF - Vaccine
IS - 19-20
ER -