Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa

被引：56

作者：

Lee, Che-Hung

Kuo, Wen-Chun

Beri, Suresh ^{[2
]}

Kapre, Subash ^{[2
]}

Joshi, Jayant S. ^{[2
]}

Bouveret, Nancy ^{[3
]}

LaForce, F. Marc ^{[3
]}

Frasch, Carl E. ^{[1
]}

机构：

[1] US FDA, Lab Bacterial Polysaccharides, HFM 428, DBPAP,OVRR,CBER,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

[2] Serum Inst India Ltd, Pune, Maharashtra, India

[3] Meningitis Vaccine Project, Ferney Voltaire, France

来源：

VACCINE | 2009年 / 27卷 / 05期

关键词：

Vaccine; Conjugate; Polysaccharide; NEISSERIA-MENINGITIDIS SEROGROUP; SUB-SAHARAN AFRICA; CAPSULAR POLYSACCHARIDE; O-ACETYLATION; GROUP-B; ANTIBODY; IMMUNIZATION; PERSISTENCE; PREVENTION; EPIDEMIC;

D O I：

10.1016/j.vaccine.2008.11.065

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Periodic epidemics of group A meningococcal (Mn A) meningitis continue to occur in sub-Saharan Africa. For its prevention, a Mn A polysaccharide (PS)-tetanus toxoid (TT) conjugate vaccine was developed using reductive amination of polysaccharicle aldehydes and toxoid hydrazides. In mouse immunization studies, a schedule of three bi-weekly s.c. immunizations of 0.1 or 1 mu g of the conjugate (PS content) without an adjuvant induced serum antibody levels of >10,000 units/mL measured by enzyme-linked immunosorbent assay (ELISA) as compared to similar to 100 units/mL in PS control mice. The elicited antibodies were active in bactericidal assays using either baby rabbit or human complement (titers >1500 compared to similar to 200 for the PS control group). The synthesis process is reproducible and scalable, and has been successfully used for manufacturing a Mn A PS-TT conjugate vaccine based on a paradigm of shared manufacturing with transfer of new technology [Jodar L, LaForce FM, Ceccarini C, Aguado T, Granoff DM. Meningococcal conjugate vaccine for Africa: a model for development of new vaccine for the poorest countries. Lancet 2003, 361:1092-4]. A phase 1 clinical trial of the manufactured Men A-TT conjugate vaccine has been successfully carried out in adults in India, and a phase 2 clinical trial in young children is currently underway in Africa. Published by Elsevier Ltd.

引用

页码：726 / 732

页数：7

共 35 条

[1] Effect of O acetylation of Neisseria meningitidis serogroup A capsular polysaccharide on development of functional immune responses [J].

Berry, DS ;

Lynn, F ;

Lee, CH ;

Frasch, CE ;

Bash, MC .

INFECTION AND IMMUNITY, 2002, 70 (07) :3707-3713

[2]

BUNDLE DR, 1974, J BIOL CHEM, V249, P2275

[3]

FRASCH CE, 2004, P 14 INT PATH NEISS, P159

[4] Prevention of meningococcal disease [J].

Gardner, Pierce .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (14) :1466-1473

[5] THE DURATION OF THE ANTIBODY-RESPONSE TO MENINGOCOCCAL VACCINATION IN AN AFRICAN VILLAGE [J].

GREENWOOD, BM ;

WHITTLE, HC ;

BRADLEY, AK ;

FAYET, MT ;

GILLES, HM .

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, 1980, 74 (06) :756-760

[6] Selection of an immunogenic peptide mimic of the capsular polysaccharide of Neisseria meningitidis serogroup A using a peptide display library [J].

Grothaus, MC ;

Srivastava, N ;

Smithson, SL ;

Kieber-Emmons, T ;

Williams, DB ;

Carlone, GM ;

Westerink, MAJ .

VACCINE, 2000, 18 (13) :1253-1263

[7] Prospects for vaccine prevention of meningococcal infection [J].

Harrison, LH .

CLINICAL MICROBIOLOGY REVIEWS, 2006, 19 (01) :142-+

[8] DERIVATIZATION OF CROSS-LINKED POLYACRYLAMIDE BEADS . CONTROLLED INTRODUCTION OF FUNCTIONAL GROUPS FOR PREPARATION OF SPECIAL-PURPOSE, BIOCHEMICAL ADSORBENTS [J].

INMAN, JK ;

DINTZIS, HM .

BIOCHEMISTRY, 1969, 8 (10) :4074-&

[9] Preparation and characterization of group A meningococcal capsular polysaccharide conjugates and evaluation of their immunogenicity in mice [J].

Jin, ZG ;

Chu, CY ;

Robbins, JB ;

Schneerson, R .

INFECTION AND IMMUNITY, 2003, 71 (09) :5115-5120

[10] Meningococcal conjugate vaccine for Africa:: a model for development of new vaccines for the poorest countries [J].

Jódar, L ;

LaForce, FM ;

Ceccarini, C ;

Aguado, T ;

Granoff, DM .

LANCET, 2003, 361 (9372) :1902-1904

← 1 2 3 4 →