Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae
Pneumonia remains the single leading cause of childhood death worldwide. Despite the commercial availability of multiple pneumococcal conjugate vaccines (PCVs), high dosage cost and supply shortages prevent PCV delivery to much of the developing world. The current work presents high-yield pneumococc...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2017-03-01
|
| Series: | Synthetic and Systems Biotechnology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X16300436 |
| _version_ | 1797203180921028608 |
|---|---|
| author | Allison E.B. Turner Jonas E. Gerson Helen Y. So Daniel J. Krasznai Adrienne J. St. Hilaire Donald F. Gerson |
| author_facet | Allison E.B. Turner Jonas E. Gerson Helen Y. So Daniel J. Krasznai Adrienne J. St. Hilaire Donald F. Gerson |
| author_sort | Allison E.B. Turner |
| collection | DOAJ |
| description | Pneumonia remains the single leading cause of childhood death worldwide. Despite the commercial availability of multiple pneumococcal conjugate vaccines (PCVs), high dosage cost and supply shortages prevent PCV delivery to much of the developing world. The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development. The 13-valent pneumococcal conjugate vaccine (PCV-13) investigated in this research incorporated serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Pneumococcal polysaccharides (PnPSs) and CRM197 carrier protein were produced and purified in-house, and used to prepare PnPS-CRM conjugates using unique, cyanide-free, in vacuo glycation conjugation methods. In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein. In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13, Prevnar®13 (Pfizer, USA). A boost dose was provided to all groups post-dose 1 at t = 14 days. Post-dose 2 results at t = 28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable. Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes, with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2. As a result, the novel polysaccharide-protein conjugates developed in this work are highly promising for use in human PCV development. The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines. |
| first_indexed | 2024-04-24T08:15:14Z |
| format | Article |
| id | doaj.art-a84f0ccc61bd4fa9928742dc0e1d1b45 |
| institution | Directory Open Access Journal |
| issn | 2405-805X |
| language | English |
| last_indexed | 2024-04-24T08:15:14Z |
| publishDate | 2017-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj.art-a84f0ccc61bd4fa9928742dc0e1d1b452024-04-17T04:13:33ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2017-03-0121495810.1016/j.synbio.2016.12.002Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniaeAllison E.B. Turner0Jonas E. Gerson1Helen Y. So2Daniel J. Krasznai3Adrienne J. St. Hilaire4Donald F. Gerson5Vaccine Research and Development, PnuVax Incorporated Headquarters, 134 Albert St., Kingston, Ontario, K7L 3V2, CanadaVaccine Research and Development, PnuVax Incorporated Headquarters, 134 Albert St., Kingston, Ontario, K7L 3V2, CanadaVaccine Research and Development, PnuVax Incorporated Laboratories, 6000 Royalmount Ave., Montreal, Quebec, H4P 2T1, CanadaVaccine Research and Development, PnuVax Incorporated Laboratories, 6000 Royalmount Ave., Montreal, Quebec, H4P 2T1, CanadaVaccine Research and Development, PnuVax Incorporated Laboratories, 6000 Royalmount Ave., Montreal, Quebec, H4P 2T1, CanadaVaccine Research and Development, PnuVax Incorporated Headquarters, 134 Albert St., Kingston, Ontario, K7L 3V2, CanadaPneumonia remains the single leading cause of childhood death worldwide. Despite the commercial availability of multiple pneumococcal conjugate vaccines (PCVs), high dosage cost and supply shortages prevent PCV delivery to much of the developing world. The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development. The 13-valent pneumococcal conjugate vaccine (PCV-13) investigated in this research incorporated serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Pneumococcal polysaccharides (PnPSs) and CRM197 carrier protein were produced and purified in-house, and used to prepare PnPS-CRM conjugates using unique, cyanide-free, in vacuo glycation conjugation methods. In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein. In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13, Prevnar®13 (Pfizer, USA). A boost dose was provided to all groups post-dose 1 at t = 14 days. Post-dose 2 results at t = 28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable. Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes, with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2. As a result, the novel polysaccharide-protein conjugates developed in this work are highly promising for use in human PCV development. The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.http://www.sciencedirect.com/science/article/pii/S2405805X16300436PneumoniaVaccine developmentPCVPneumococcal conjugate vaccinePolysaccharideCarrier proteinIn vacuo glycation |
| spellingShingle | Allison E.B. Turner Jonas E. Gerson Helen Y. So Daniel J. Krasznai Adrienne J. St. Hilaire Donald F. Gerson Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae Synthetic and Systems Biotechnology Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation |
| title | Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae |
| title_full | Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae |
| title_fullStr | Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae |
| title_full_unstemmed | Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae |
| title_short | Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S. pneumoniae |
| title_sort | novel polysaccharide protein conjugates provide an immunogenic 13 valent pneumococcal conjugate vaccine for s pneumoniae |
| topic | Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X16300436 |
| work_keys_str_mv | AT allisonebturner novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae AT jonasegerson novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae AT helenyso novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae AT danieljkrasznai novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae AT adriennejsthilaire novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae AT donaldfgerson novelpolysaccharideproteinconjugatesprovideanimmunogenic13valentpneumococcalconjugatevaccineforspneumoniae |