In:
The Journal of Immunology, The American Association of Immunologists, Vol. 196, No. 1_Supplement ( 2016-05-01), p. 208.12-208.12
Abstract:
Vibrio cholerae causes an acute diarrheal disease estimated to lead to 3 to 5 million cases of cholera and over 100,000 deaths annually. Vaccine-induced immunity rapidly wanes and provides only partial protection. In contrast, natural infection induces 90–100 % protection for up to 10 years. However, it remains unknown why current vaccines are markedly less effective. Understanding mucosal humoral immunity and mechanisms regulating homing of immune cells to mucosal tissues in humans is of key importance, not only for V. cholerae infection, but for many other pathogens with a mucosal route of infection. To better understand the immune response induced by natural infection, we have characterized acute plasmablast responses in infected adults at the ICDDR, b in Dhaka, Bangladesh. To understand these potent responses in more detail we have generated a panel of 150 human monoclonal antibodies from plasmablasts isolated from six patients. These antibodies have provided a unique insight into the dynamics and variability of the functional characteristics of antibody responses to cholera, in terms of toxin neutralization, direct vibriocidal activity, the ability to induce bacterial agglutination or interfere with bacterial propagation. Furthermore, the fine specificity of these antibodies raise interesting questions about the longevity of B cell memory against bacterial polysaccharides. These studies provide unprecedented insight into heterogeneity of the acute plasmablasts responses to cholera, the ability to provide long-lived immunity after infection is resolved and the antigenic specificity of the BCR, at a single cell level. These findings may instruct future vaccine development for this important human pathogen.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.196.Supp.208.12
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2016
detail.hit.zdb_id:
1475085-5
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