Antigen-specific memory B-cell responses to enterotoxigenic Escherichia coli infection in Bangladeshi adults.
BACKGROUND
Multiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. However, the precise mechanism of protection against ETEC infection is still unknown. Therefore, memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection.


METHODS
In this study, we investigated the heat labile toxin B subunit (LTB) and colonization factor antigens (CFA/I and CS6) specific IgA and IgG memory B cell responses in Bangladeshi adults (n = 52) who were infected with ETEC. We also investigated the avidity of IgA and IgG antibodies that developed after infection to these antigens.


RESULTS
Patients infected with ETEC expressing LT or LT+heat stable toxin (ST) and CFA/I group or CS6 colonization factors developed LTB, CFA/I or CS6 specific memory B cell responses at day 30 after infection. Similarly, these patients developed high avidity IgA and IgG antibodies to LTB, CFA/I or CS6 at day 7 that remained significantly elevated at day 30 when compared to the avidity of these specific antibodies at the acute stage of infection (day 2). The memory B cell responses, antibody avidity and other immune responses to CFA/I not only developed in patients infected with ETEC expressing CFA/I but also in those infected with ETEC expressing CFA/I cross-reacting epitopes. We also detected a significant positive correlation of LTB, CFA/I and CS6 specific memory B cell responses with the corresponding increase in antibody avidity.


CONCLUSIONS
This study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to LTB and colonization factor CFA/I and CS6 antigens that could mediate anamnestic responses on re-exposure to ETEC and may help in understanding the requirements to design an effective vaccination strategies.
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Mohammad Murshid
MM
Alam
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Amena
A
Aktar
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Sadia
S
Afrin
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Mohammad Arif
MA
Rahman
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Sarmin
S
Aktar
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Taher
T
Uddin
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
M Arifur
MA
Rahman
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Deena
D
Al Mahbuba
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Fahima
F
Chowdhury
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Ashraful Islam
AI
Khan
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Taufiqur Rahman
TR
Bhuiyan
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Yasmin Ara
YA
Begum
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Edward T
ET
Ryan
Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
Stephen B
SB
Calderwood
Gothenburg University Vaccine Research Institute (GUVAX), Department of Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden.
Ann-Mari
AM
Svennerholm
Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Firdausi
F
Qadri
D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D001459:Bangladesh; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D008297:Male
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C098406:CS6 antigen, E coli; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D036781:Fimbriae Proteins; C027538:heat-labile enterotoxin, E coli