Naturally-occurring human serum antibodies to inner core lipopolysaccharide epitopes of Neisseria meningitidis protect against invasive meningococcal disease caused by isolates displaying homologous inner core structures.
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 (HepI) and second heptose (HepII) 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 C3b, 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.
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK.
Anne
A
Jäkel
Joyce S
JS
Plested
J Claire
JC
Hoe
Katherine
K
Makepeace
Margaret-Anne J
MA
Gidney
Suzanne
S
Lacelle
Frank
F
St Michael
Andrew D
AD
Cox
James C
JC
Richards
E Richard
ER
Moxon
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000302:isolation & purification; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology*; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000276:immunology*; D051381:Rats; D015610:Serum Bactericidal Test; D055815:Young Adult
D000907:Antibodies, Bacterial; D000939:Epitopes; D007074:Immunoglobulin G; D008070:Lipopolysaccharides