Potential of Recombinant Opa Proteins as Vaccine Candidates against Hyperinvasive Meningococci

被引：19

作者：

Callaghan, M. J. ^{[1
]}

Lewis, S. ^{[1
]}

Sadarangani, M. ^{[1
]}

Bailey, S. E. S. ^{[2
]}

Chan, H. ^{[3
]}

Ferguson, D. J. P. ^{[4
]}

Derrick, J. P. ^{[2
]}

Feavers, I. ^{[3
]}

Maiden, M. C. ^{[5
]}

Pollard, A. J. ^{[1
]}

机构：

[1] Univ Oxford, Dept Paediat, Ctr Clin Vaccinol & Trop Med, Churchill Hosp, Oxford OX3 7LJ, England

[2] Univ Manchester, Fac Life Sci, Manchester Interdisciplinary Bioctr, Manchester M1 7DN, Lancs, England

[3] NIBSC, Div Bacteriol, Potters Bar EN6 3QG, Herts, England

[4] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England

[5] Univ Oxford, Dept Zool, Oxford OX1 3SY, England

来源：

INFECTION AND IMMUNITY | 2011年 / 79卷 / 07期

关键词：

OUTER-MEMBRANE PROTEINS; H-BINDING PROTEIN; NEISSERIA-MENINGITIDIS; OPACITY PROTEINS; CONJUGATE VACCINES; VESICLE VACCINE; PATHOGENIC NEISSERIAE; BACTERICIDAL ACTIVITY; ENDOTHELIAL-CELLS; PHASE VARIATION;

D O I：

10.1128/IAI.01338-10

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Neisseria meningitidis causes half a million cases of septicemia and meningitis globally each year. The opacity (Opa) integral outer membrane proteins from N. meningitidis are polymorphic and highly immunogenic. Particular combinations of Opa proteins are associated with the hyperinvasive meningococcal lineages that have caused the majority of serogroup B and C meningococcal disease in industrialized countries over the last 60 years. For the first time, this genetic structuring of a diverse outer membrane protein family has been used to select a novel combination of representative antigens for immunogenicity testing. Fourteen recombinant Opa variants were produced and used in murine immunizations inducing an increase in specific antimeningococcal total IgG levels. All 14 Opa proteins elicited bactericidal antibodies against at least one hyperinvasive meningococcal isolate, and most isolates from each hyperinvasive lineage were killed by at least one Opa antiserum at a titer of 1: 16 or greater. Cross-reactive bactericidal antibody responses were observed among clonal complexes. A theoretical coverage of 90% can be achieved by using a particular combination of 6 Opa proteins against an isolate collection of 227 recent United Kingdom disease cases. This study indicates the potential of Opa proteins to provide broad coverage against multiple meningococcal hyperinvasive lineages.

引用

页码：2810 / 2818

页数：9

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