An integrated molecular and immunological approach towards a meningococcal group B vaccine

Lifely, M R; Moreno, Carlos; Lindon, John C.

doi:10.1016/0264-410x(87)90004-1

Cited by 37 publications

(35 citation statements)

References 43 publications

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“…It is likely that such extended and regularly repeating structures could be disrupted by random cleavage of polymer chains, particularly when the molecular mass is reduced below a certain critical degree of polymerization. It has been postulated that some bacterial polysaccharide capsular antigens may contain conformational epitopes that are mass-dependent, and the correlation of an effective immunologic response with high mass has been demonstrated for meningococcal type B polysialic acid (44) and for other capsular antigens (45)(46)(47). In order to minimize perturbation to the native capsule, we felt it was important to develop a purification scheme that retained as closely as possible the native size in the event that mass-dependent conformational effects were important for induction of neutralizing antibody.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

Joyce

Cook

Chabot

et al. 2006

Journal of Biological Chemistry

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The capsular polypeptide of Bacillus anthracis is composed of a unique polyglutamic acid polymer in which D-glutamate monomers are joined by ␥-peptidyl bonds. The capsule is poorly immunogenic, and efforts at exploiting the polymer for vaccine development have focused on increasing its inherent immunogenicity through chemical coupling to immune-stimulating protein carriers. The usual strategy has employed carbodiimide-based condensing reagents for activation of free ␣-carboxyl groups, despite reports that this chemistry may lead to chain scission. We have purified the high molecular mass capsule to >95% homogeneity and have demonstrated that the polymer contains >99% poly-␥-D-glutamic acid. The predominant structure of the polymer as assessed by circular dichroism and multiangle laser light scattering was unordered at near-neutral pH. We investigated the effects of various activation chemistries, and we demonstrated that carbodiimide treatment under aqueous conditions results in significant cleavage of the ␥-peptidyl bond, whereas scission is significantly reduced in nonaqueous polar solvents, although undesired side chain modification was still observed. An activation chemistry was developed using the triazine-based reagent 4-(4,6-dimethoxy (1,3,5)triazin-2-yl)-4-methylmorpholinium chloride, which allowed for controlled and reproducible derivatization of ␣-carbonyls. In a two-pot reaction scheme, activated capsule was derivatized with a sulfhydryl-reactive heterobifunctional moiety and was subsequently coupled to thiolated carrier protein. This conjugate elicited very high capsule-specific immune titers in mice. More importantly, mice immunized with conjugated capsule exhibited good protection against lethal challenge from a virulent B. anthracis strain in two models of infection. We also showed, for the first time, that treatment of capsule with carbodiimide significantly reduced recognition by capsule-specific antisera concurrent with the reagent-induced reduction of polymer mass. The data suggested that for vaccine development, maintenance of the high mass of the polymer may be important.

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Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

Joyce

Cook

Chabot

et al. 2006

Journal of Biological Chemistry

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“…However, serogroup B CPS is poorly immunogenic and induces only a transient antibody response of a predominantly immunoglobulin M isotype (3,14,42). Other than capsular antigens, outer membrane proteins (OMPs), primarily class 1 to 5, have been studied as potential vaccine candidates (32).…”

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Serosubtypes and PorA Types of Neisseria meningitidis Serogroup B Isolated in Brazil during 1997-1998: Overview and Implications for Vaccine Development

et al. 2001

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Meningococcal disease caused by N. meningitidis serogroup B (MenB) has been endemic in Brazil since 1997. In this study, we determined the prevalence of serosubtypes of MenB isolated in 10 Brazilian states and the Federal District during 1997 and 1998 and investigated the extent of PorA VR sequence variation among the most prevalent serosubtypes to evaluate the possible use of an outer membrane vesicle (OMV)-, PorA-based vaccine to prevent meningococcal disease in Brazil. During this period, a total of 8,932 cases of meningococcal disease were reported. Only 42% (n ‫؍‬ 3,751) of the reported cases were laboratory confirmed, and about 60% (n ‫؍‬ 2,255) of those were identified as MenB. Among 1,297 MenB strains selected for this study, the most prevalent serosubtypes were P1.19,15 (66%), P1.7,1 (11%), and P1.7,16 (4%). PorA VR typing showed that 91% of the P1.19,15 strains analyzed had VR1 and VR2 sequences identical to those of the prototype strain. No sequence variation was detected among the 40 strains representing all isolated MenB P1.7,16 strains in the three southern states, where this serosubtype accounts for 75% of the serosubtypes identified. Similarly, all P1.7,1 strains were identified by PorA typing as P1.7-1,1. Although further improvements in the reporting of cases and collection of strains in Brazil are needed, our data suggest that a trivalent OMV-based vaccine prepared with PorA types P1.19,15, P1.7-1,1, and P1.7,16 may be appropriate to control serogroup B meningococcal disease in most of the Brazilian states.

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“…Neisseria meningitidis ou meningococo é classificada em 12 sorogrupos de acordo com a especificidade imunológica do polissacáride capsular 31 . Diferenças imunológicas entre as principais classes de proteínas da membrana externa são a base para a classificação do microrganismo em sorotipos e subtipos 16,20 , sendo os imunotipos determinados pela especificidade imunológica das molé-culas de lipoligossacáride 46 .…”

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“…Diferente dos demais polissacárides, a resposta imune contra o polissacáride de N. meningitidis B caracteriza-se pela produção de IgM, tanto em portadores quanto em pacientes com doença sistêmica 31,35 . Da mesma forma, o polissacáride B purificado e de alto peso molecular induz primariamente à produção de IgM 19,31 , mesmo quando conjugado a proteínas carreadoras e adsorvidos ao hidróxido de alumínio 19,35 .…”

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“…Da mesma forma, o polissacáride B purificado e de alto peso molecular induz primariamente à produção de IgM 19,31 , mesmo quando conjugado a proteínas carreadoras e adsorvidos ao hidróxido de alumínio 19,35 . Esta pobre imunogenicidade é atribuída, principalmente, à semelhança antigênica do polissacáride B com glicolípides e glicoproteínas presentes em células humanas, à sensibilidade a neuraminidases do organismo humano e a instabilidade tridimensional da molécula 31 .…”

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Imunidade conferida por vacinas anti-meningocócicas

Milagres

Melles

1993

Rev. Saúde Pública

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A. Imunidade conferida por vacinas anti-meningocócicas. Rev. Saúde Pública, 27: 221-6,1993. Em razão da recente epidemia de doença meningocócica causada por N. meningitidis B na Grande São Paulo, Brasil, foi feita revisão das epidemias dessa doença ocorridas no Brasil desde o início do século e uma análise das vacinas atuais contra N. meningitidis A, C, Y e W135. Também são discutidos os mais recentes avanços no desenvolvimento e aplicação de vacina contra M meningitidis B, um desafio constante para os maiores centros de pesquisa de todo o mundo.Descritores: Neisseria meningitidis, imunologia. Vacinas bacterianas, imunologia. Meningite meningocócica, prevenção.

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An integrated molecular and immunological approach towards a meningococcal group B vaccine

Cited by 37 publications

References 43 publications

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

Serosubtypes and PorA Types of Neisseria meningitidis Serogroup B Isolated in Brazil during 1997-1998: Overview and Implications for Vaccine Development

Imunidade conferida por vacinas anti-meningocócicas

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