Biomarkers of Environmental Enteropathy are Positively Associated with Immune Responses to an Oral Cholera Vaccine in Bangladeshi Children.
Environmental enteropathy (EE) is a poorly understood condition that refers to chronic alterations in intestinal permeability, absorption, and inflammation, which mainly affects young children in resource-limited settings. Recently, EE has been linked to suboptimal oral vaccine responses in children, although immunological mechanisms are poorly defined. The objective of this study was to determine host factors associated with immune responses to an oral cholera vaccine (OCV). We measured antibody and memory T cell immune responses to cholera antigens, micronutrient markers in blood, and EE markers in blood and stool from 40 Bangladeshi children aged 3-14 years who received two doses of OCV given 14 days apart. EE markers included stool myeloperoxidase (MPO) and alpha anti-trypsin (AAT), and plasma endotoxin core antibody (EndoCab), intestinal fatty acid binding protein (i-FABP), and soluble CD14 (sCD14). We used multiple linear regression analysis with LASSO regularization to identify host factors, including EE markers, micronutrient (nutritional) status, age, and HAZ score, predictive for each response of interest. We found stool MPO to be positively associated with IgG antibody responses to the B subunit of cholera toxin (P = 0.03) and IgA responses to LPS (P = 0.02); plasma sCD14 to be positively associated with LPS IgG responses (P = 0.07); plasma i-FABP to be positively associated with LPS IgG responses (P = 0.01) and with memory T cell responses specific to cholera toxin (P = 0.01); stool AAT to be negatively associated with IL-10 (regulatory) T cell responses specific to cholera toxin (P = 0.02), and plasma EndoCab to be negatively associated with cholera toxin-specific memory T cell responses (P = 0.02). In summary, in a cohort of children 3-14 years old, we demonstrated that the majority of biomarkers of environmental enteropathy were positively associated with immune responses after vaccination with an OCV.
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Muhammad Ikhtear
MI
Uddin
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Shahidul
S
Islam
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Naoshin S
NS
Nishat
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Motaher
M
Hossain
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Tanzeem Ahmed
TA
Rafique
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Rasheduzzaman
R
Rashu
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Mohammad Rubel
MR
Hoq
Department of Internal Medicine, Division of Epidemiology, University of Utah, School of Medicine, Salt Lake City, Utah, United States of America.
Yue
Y
Zhang
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Amit
A
Saha
Department of Immunology and Infectious Diseases, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, United States of America.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.
Jason B
JB
Harris
Department of Immunology and Infectious Diseases, 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.
Stephen B
SB
Calderwood
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Taufiqur Rahman
TR
Bhuiyan
Department of Immunology and Infectious Diseases, 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.
Edward T
ET
Ryan
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.|Department of Internal Medicine, Division of Infectious Diseases, University of Utah, School of Medicine, Salt Lake City, Utah, United States of America.|Department of Pathology, Division of Microbiology and Immunology, University of Utah, School of Medicine, Salt Lake City, Utah, United States of America.
Daniel T
DT
Leung
Mucosal Immunology and Vaccinology Laboratory, Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
Firdausi
F
Qadri
D000284:Administration, Oral; D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D001459:Bangladesh / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015704:CD4 Antigens / Q000032:analysis / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D016753:Interleukin-10 / Q000276:immunology; D007410:Intestinal Diseases / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D018977:Micronutrients / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000032:analysis / Q000097:blood; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D041241:Vibrio cholerae O1 / Q000276:immunology
D000907:Antibodies, Bacterial; D015415:Biomarkers; D015704:CD4 Antigens; D022121:Cholera Vaccines; D016207:Cytokines; C508609:IL10 protein, human; D007074:Immunoglobulin G; D018977:Micronutrients; D011994:Recombinant Proteins; D015164:Vaccines, Inactivated; C076613:recombinant soluble CD4; D016753:Interleukin-10; D009195:Peroxidase