Safety and Immunogenicity of a Neisseria meningitidis Type 2 Protein Vaccine in Animals and Humans

Zollinger, Wendell D.; Mandrell, Robert E.; Altieri, Patricia L.; Berman, Sanford; Lowenthal, Joseph P.; Artenstein, Malcolm S.

doi:10.1093/infdis/137.6.728

Cited by 85 publications

(62 citation statements)

References 23 publications

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“…Purified high molecular weight group B polysaccharide has been reported to lack substantial immunogenicity in man (5). This result, together with evidence of poor antibody responses to the group B polysaccharide after natural group B infection (6,7), has led to the study of noncapsular surface antigens as potential vaccines (8)(9)(10)(11). The serotype 2 outer membrane protein has been of particular interest because in recent years serotype 2 strains have been responsible for a high percentage of group B disease (3,12,13), and the outer membrane proteins can be separated from the toxic lipopolysaccharide (LPS)1 in a form that is both immunogenic and protective in animals (8,11).…”

Section: Introductionmentioning

confidence: 99%

Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

Zollinger¹,

Mandrell²,

Griffiss³

et al. 1979

J. Clin. Invest.

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194

118

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A B S T R A C T A noncovalent complex of meningococcal group B polysaccharide and type 2 outer membrane protein has been characterized and its potential as a vaccine against group B meningococcal disease investigated. The polysaccharide component was found to have a partition coefficient, Kd, of 0.34 on Sepharose CL-4B in the presence of sodium deoxycholate. The protein consisted of four to five major proteins including the principal outer membrane protein. Hydrophobic binding between the protein and polysaccharide was demonstrated by gel filtration and isopycnic CsCl density gradient centrifugation and found to involve all of the proteins. After demonstrating safety and immunogenicity in animals, two lots of vaccine were tested in a total of eight volunteers. Two 120-,ug doses were given subcutaneously at 0 and 5 wk. Mild local reactions occurred in all eight volunteers, but no systemic reactions were observed. 2 wk after the first dose, six of the volunteers had increased levels of bactericidal antibodies against both the group B polysaccharide and the outer membrane proteins. Antibody rises to the group B polysaccharide (mean 6-fold) were confirmed by passive hemagglutination assays and rises to the proteins (mean 10-fold) by a solid phase radioimmunoassay. The second dose resulted in little or no increase in antibody titers. Antibody titers declined over a period of 14 wk but mostly remained above preimmunization levels. Bactericidal antibodies with specificity for the group B polysaccharide were mostly of the immunoglobulin (Ig)M class, and were directed against a determinant associated only with high molecular weight polysaccharides. We conclude that both the group B polysaccharide and the outer membrane protein are immunogenic in man when presented as a complex and that the complex warrants further testing and development as a vaccine against group B meningococcal disease.

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Section: Introductionmentioning

confidence: 99%

Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

Zollinger¹,

Mandrell²,

Griffiss³

et al. 1979

J. Clin. Invest.

Self Cite

194

118

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“…The serotype 2 protein extracted from strain M986 (B, 2a) is protective in animal models Craven and Frasch, 1979) but does not appear to be a satisfactory immunogen in humans (Zollinger et al, 1978;Frasch, 1979). However, a more soluble protein, or protein complexed with group B polysaccharide appear to be more promising as vaccines (Zollinger et al, 1979;Peppler and Frasch, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, group B capsular polysaccharide is not immunogenic in man (Wyle et al, 1972); consequently meningococcal non-capsular cell surface antigens including protein and complexes of protein and group B polysaccharide are being investigated as possible vaccines against disease caused by group B meningococci (Zollinger et al, 1978;Frasch, 1979;Zollinger et al, 1979;.…”

Section: Introductionmentioning

confidence: 99%

Immunogenic and protective properties of meningococcal serotype 2a protein in the hen-embryo model

Ashton¹,

Ryan²,

Diena³

et al. 1983

Journal of Medical Microbiology

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“…In the specific case of meningococcal OMV based vaccines the RPT has been used historically to measure the pyrogenic dose of the vaccine, i.e., the vaccine is diluted until a pyrogenic response is no longer seen in rabbits (Fisseha et al, 2005;Frasch and Peppler, 1982;Tsai et al, 1989;Zollinger et al, 1978). Meningococcal OMVs are composed of outer membrane proteins, lipids and lipopolysaccharide (LPS) or endotoxin.…”

Section: Use Of the Rpt In Meningococcal Omv Based Productsmentioning

confidence: 99%

Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines

Vipond

Findlay

Feavers

et al. 2016

ALTEX

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SummaryThe rabbit pyrogen test was developed in the early 1900's to detect contaminating pyrogens in parenteral medicines. Since its conception alternative methods with improved sensitivity, relevancy and which are ethically more acceptable have been developed. However, the test is still a current pharmacopeial method and is used to evaluate the pyrogen content of some vaccines. In this article the limitations and pitfalls of using the test to measure pyrogenicity of vaccines containing outer membrane vesicles are described. The method is unsuitable as a safety test for these products due to the high levels of endotoxin present in the vaccine which generate a pyrogenic response in rabbits when delivered intravenously without dilution. Its use as a consistency test is also ambiguous as the test gives a qualitative rather than quantitative response, and the rabbit models are highly variable. In addition there is evidence that measuring the temperature rise of the animals over three hours does not capture the maximum fever response. Finally the article considers the use of alternative methods and the validity of animal models when applying a consistency based approach for assessing the quality of licensed products.

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Safety and Immunogenicity of a Neisseria meningitidis Type 2 Protein Vaccine in Animals and Humans

Cited by 85 publications

References 23 publications

Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

Immunogenic and protective properties of meningococcal serotype 2a protein in the hen-embryo model

Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines

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