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

Lee, Che-Hung; Kuo, Wen-Chun; Beri, Suresh; Kapre, Subash; Joshi, Jayant S.; Bouveret, Nancy; LaForce, F. Marc; Frasch, Carl E.

doi:10.1016/j.vaccine.2008.11.065

Cited by 68 publications

(44 citation statements)

References 26 publications

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“…Figure 2 shows the chromatograms of PS6B-OCT-mPspA (top) and PS6B-PspA (bottom) with 3 overlapping chromatograms each: (i) nonconju- gated rPspA1, (ii) nonconjugated PS6B, and (iii) the conjugates. The relative amounts of the conjugated and nonconjugated PSs were measured from the column elution for calculation of the conjugation yields (42). The chromatograms shown for the nonconjugated compounds, rPspA1 and PS6B, are representative of a column loaded with 5 mg, and the chromatograms shown for the conjugates are representative of 25 mg of PS6B.…”

Section: Resultsmentioning

confidence: 99%

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Perciani

Barazzone

Goulart

et al. 2013

Clin Vaccine Immunol

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bDespite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface protein A (rPspA), a well-known protective antigen from Streptococcus pneumoniae, were covalently attached by two conjugation methods. The conjugation methodology developed by our laboratory, employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an activating agent through carboxamide formation, was compared with reductive amination, a classical methodology. DMT-MM-mediated conjugation was shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate fraction with reductive amination. The influence of the conjugation process on the rPspA1 structure was assessed by circular dichroism. According to our results, both conjugation processes reduced the alpha-helical content of rPspA; reduction was more pronounced when the reaction between the polysaccharide capsule and rPspA1 was promoted between the carboxyl groups than the amine groups (46% and 13%, respectively). Regarding the immune response, both conjugates induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest that the secondary structure of PspA1, as well as its reactive groups (amine or carboxyl) involved in the linkage to PS6B, may not play an important role in eliciting a protective immune response to the antigens.

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Section: Resultsmentioning

confidence: 99%

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Perciani

Barazzone

Goulart

et al. 2013

Clin Vaccine Immunol

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“…Immunogenicity of the highest molecular weight pools as measured by both IgG antibody and bactericidal activity was significantly higher than for the lowest molecular weight conjugate pool. 27,28 The lowest molecular weight pool was, however, more immunogenic than a pure PS control vaccine. 64% in PsAC group; 68% in TT vaccine group), redness (13% in PsA-TT group; 16% in PsAC and TT vaccine group) and swelling (8% in PsA-TT and PsAC group; 20% in TT vaccine group).…”

Section: Clinical Development and Licensurementioning

confidence: 99%

“…A new conjugation method was developed to decrease the conjugation time and increase conjugate yields. 27 The general conjugation scheme is shown in Figure 2 and is described in detail in reference 27-30. Conjugation efficiency was improved for MenAfriVac TM by chemically activating both the PS and carrier protein (Fig.…”

Section: Vaccine Production and Quality Controlmentioning

confidence: 99%

“…Initial studies showed that the conjugated group A PS was highly immunogenic in mice, inducing much higher bactericidal antibody (about 3 logs) compared with the PS alone. 27,28 Some conjugates were size-fractionated on the gel filtration matrix, Sephacryl S-400 HR. Different molecular size pools were used to immunize mice at 0.1 μg PS per dose in 3 weekly doses.…”

Section: Clinical Development and Licensurementioning

confidence: 99%

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Development of a group A meningococcal conjugate vaccine,MenAfriVac^TM

2012

Human Vaccines & Immunotherapeutics

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“…A vaccine has been developed with the goal of eliminating epidemic meningitis from the region (1,2). Human responses to new meningococcal vaccines are evaluated serologically by several methods.…”

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confidence: 99%

Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

Bash

Lynn

Mocca

et al. 2014

Clin. Vaccine Immunol.

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A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC=) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC= and then used the SBA assay with hC= (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12-to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC= lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC=. hSBA titers determined using three independent lots of pooled hC= were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TTprimed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC= is feasible and showed that PsA-TT was highly immunogenic in African toddlers.

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

Cited by 68 publications

References 26 publications

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Development of a group A meningococcal conjugate vaccine,MenAfriVac^TM

Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

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

Cited by 68 publications

References 26 publications

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response

Development of a group A meningococcal conjugate vaccine,MenAfriVacTM

Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

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Development of a group A meningococcal conjugate vaccine,MenAfriVac^TM