Abstract
BackgroundMultiple 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.MethodologyIn 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.Principal FindingsPatients 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.ConclusionThis 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.
Highlights
Enterotoxigenic Escherichia coli (ETEC) are one of the major causes of diarrhea in developing countries, causing approximately 200 million episodes of diarrhea and 380,000 deaths every year [1,2]
This study demonstrates that natural infection with ETEC induces memory B cells and high avidity antibodies to labile toxin B subunit (LTB) and colonization factor colonization factor-I (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
Female) patients with diarrhea who were infected with ETEC
Summary
Enterotoxigenic Escherichia coli (ETEC) are one of the major causes of diarrhea in developing countries, causing approximately 200 million episodes of diarrhea and 380,000 deaths every year [1,2]. ETEC have been shown to be the second most frequently isolated bacterial pathogens after Vibrio cholerae O1 in patients with diarrhea in Dhaka, Bangladesh [5]. ETEC strains are genetically and phenotypically divergent, expressing different toxins and one or more of several different colonization factors (CFs). Multiple infections with diverse enterotoxigenic E. coli (ETEC) strains lead to broad spectrum protection against ETEC diarrhea. The precise mechanism of protection against ETEC infection is still unknown. Memory B cell responses and affinity maturation of antibodies to the specific ETEC antigens might be important to understand the mechanism of protection
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