期刊
VACCINE
卷 26, 期 51, 页码 6655-6663出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.09.041
关键词
Neisseria meningitides; Lipopolysaccharide; Affinity purified antibodies
资金
- Novartis Vaccines
- MRC
- Spencer Dayman Meningitis Laboratories, UK
- Wellcome Trust
- NIHR Biomedical Research Centre
- Medical Research Council [G0400426] Funding Source: researchfish
- MRC [G0400426] Funding Source: UKRI
Sera from healthy infants (Under 1 year old), toddlers (3-4 years) and adults (18-65 years) were assayed for their ability to bind to inner core (ic) lipopolysaccharide (LPS) epitopes of Neisseria Meningitidis. Antibodies (Abs) reacting to inner core structures, including different Substitutions of the first heptose (Hepl) and second heptose (Hell) residues of the LPS backbone, truncated and fully extended LPS glycoforms, were detected and for each Structure, these inner core antibodies showed an age-related pattern Of acquisition. A novel column-based methodology was used to affinity purify IgG antibodies in which Purified inner core LPS (derived from a Mutant MC58) was covalently linked to Sepharose 4B. Comparison of reactivity before and after affinity purification of the pooled sera showed that the Purified Abs bound to the Surface of N. meningitidis organisms displaying truncated and extended LPS with a homologous inner core region, promoted the deposition of Ob, were opsonophagocytic in vitro and decreased bacteraemia when used to passively protect infants rats. In addition, the Purified Abs were bactericidal in vitro against the mutant strain displaying truncated LPS with a homologous inner Core region. These results demonstrate that naturally occurring serum human antibodies to N. meningitidis LPS can access inner core epitopes of encapsulated organisms with a fully extended LPS. (C) 2008 Elsevier Ltd. All rights reserved.
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