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Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine
Authors:Mohammad Murshid Alam  Daniel T. Leung  Marjahan Akhtar  Mohammad Nazim  Sarmin Akter  Taher Uddin  Farhana Khanam  Deena Al Mahbuba  Shaikh Meshbahuddin Ahmad  Taufiqur Rahman Bhuiyan  Stephen B. Calderwood  Edward T. Ryan  Firdausi Qadri
Affiliation:Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesha;Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USAb;Departments of Medicinec;Microbiology and Immunobiology,d Harvard Medical School, Boston, Massachusetts, USA;Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USAe
Abstract:Antibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.
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