Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease

Kaaijk, Patricia; Straaten, Ineke van; Waterbeemd, Bas van de; Boot, Elmieke P. J.; Levels, Lonneke; Dijken, Harry H. van; Dobbelsteen, Germie P. J. M. van den

doi:10.1016/j.vaccine.2012.12.031

Cited by 45 publications

(36 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…67 In summary, these data support the use of rPorA as an adjuvant and in the development of a novel meningococcal B oral vaccine. The next-generation vaccine NonaMen induced high SBA titers against all tested MenB strains, when administered subcutaneously in rabbits and mice, regardless of whether aluminum phosphate was used as an adjuvant, 31 suggesting that an adjuvant was not necessary.…”

Section: Discussionmentioning

confidence: 97%

“…To obtain a wider coverage, vaccine strains carrying 6 (HexaMen) and 9 (NonaMen) different PorA serosubtypes have been designed. 26,31 Additionally, it has been estimated that NonaMen vaccine will probably cover 75% of the serogroup B strains present worldwide. 30 However, this will not be enough to protect from hundreds of PorA serosubtypes existing around the world.…”

Section: Discussionmentioning

confidence: 99%

“…30,31 Multiple PorA serotype vaccines have been administered as a 3-dose series in infants; nevertheless, they showed a modest efficacy. However, after a fourth dose in toddlers, a satisfactory immune response could be induced.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Oral administration of recombinantNeisseria meningitidisPorA genetically fused toH. pyloriHpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

Vásquez

Manzo

Soto

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oral administration of recombinantNeisseria meningitidisPorA genetically fused toH. pyloriHpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

Vásquez

Manzo

Soto

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…The monograph describes three methods and whole blood, peripheral blood mononuclear cells or cell lines can be used for any of these methods. MATs have been used to evaluate meningococcal OMV based vaccines (Kaaijk et al, 2013b;Stoddard et al, 2010); one of these studies used whole blood and the other the monocytic cell line MM6. The pyrogen content of the vaccines was assessed via IL-6 release in both assays and in addition TNF-α was also measured in one study.…”

Section: Measuring the Maximum Febrile Responsementioning

confidence: 99%

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

Vipond

Findlay

Feavers

et al. 2016

ALTEX

View full text Add to dashboard Cite

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.

show abstract

“…PorA with Mw of 42-45 kDa is an intramembrane cationic protein that is expressed in all the strains as a major component of the meningococcal OM [8,9]. Amino acid sequences of this protein are relatively conserved among different strains and are composed of 8 hydrophilic extracellular loops [9,10]. Two of these loops possess highly immunogenic properties (loop1 and loop4) and stimulate immune responses to induce the production of antibodies.…”

Section: Introductionmentioning

confidence: 99%

Cloning and expression of porA gene as the first step of a vaccine candidate study against Neisseria meningitidis serogroup A infection

Afrough

Behrouzi

Davari

et al. 2016

vacres

View full text Add to dashboard Cite

Introduction: Neisseria meningitidis is a major causative agent of bacterial septicemia and meningitis in human. PorA is a major component of the outer membrane of N. meningitidis and functions as a cationic Porin. This study aimed to clone and determine the expression of PorA as the first step for producing a proper antigen in a vaccine study against N. meningitidis. Methods: An approximately 1200-bp fragment of porA gene was amplified by PCR using N. meningitidis serogroup A genomic DNA and then cloned into prokaryotic expression vector pET-28a. The resulting construct (pET28a-porA plasmid) was transformed into competent E.coli BL21 cells for expression of recombinant protein. The proper overexpression of the recombinant protein was verified by SDS-PAGE and Western Blotting. Results: Cloning of porA was confirmed by colony-PCR and enzymatic digestion. The nucleotide sequence homology of the cloned porA gene was 97% , compared to the reference gene (NCBI GenBank accession number AL157959.1). The prokaryotic expression system (pET28a-porA-BL21) could produce our 45-kDa target recombinant protein, efficiently. Conclusion: The prokaryotic expression system and conditions used in this study provides an applicable method for producing recombinant PorA and possibly many other bacterial outer membrane proteins for future vaccine studies.

show abstract

Preclinical safety and immunogenicity evaluation of a nonavalent PorA native outer membrane vesicle vaccine against serogroup B meningococcal disease

Cited by 45 publications

References 39 publications

Oral administration of recombinantNeisseria meningitidisPorA genetically fused toH. pyloriHpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

Oral administration of recombinantNeisseria meningitidisPorA genetically fused toH. pyloriHpaA antigen increases antibody levels in mouse serum, suggesting that PorA behaves as a putative adjuvant

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

Cloning and expression of porA gene as the first step of a vaccine candidate study against Neisseria meningitidis serogroup A infection

Contact Info

Product

Resources

About