Preclinical studies on new proteins as carrier for glycoconjugate vaccines

Abstract Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids,...

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Veröffentlicht in:Vaccine 2016-07, Vol.34 (35), p.4235-4242
Hauptverfasser: Tontini, M, Romano, M.R, Proietti, D, Balducci, E, Micoli, F, Balocchi, C, Santini, L, Masignani, V, Berti, F, Costantino, P
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container_end_page 4242
container_issue 35
container_start_page 4235
container_title Vaccine
container_volume 34
creator Tontini, M
Romano, M.R
Proietti, D
Balducci, E
Micoli, F
Balocchi, C
Santini, L
Masignani, V
Berti, F
Costantino, P
description Abstract Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197 , the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae . Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides.
doi_str_mv 10.1016/j.vaccine.2016.06.039
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Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197 , the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae . Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2016.06.039</identifier><identifier>PMID: 27317455</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animals ; Antibodies, Bacterial - blood ; Antibody Formation ; Antigens ; Candidates ; Carrier protein ; Carrier Proteins - chemistry ; Chromatography ; CRM197 ; Diphtheria ; E coli ; Genomes ; Glucans - chemistry ; Glycoconjugates ; Glycoconjugates - chemistry ; Haemophilus influenzae ; Immunogenicity ; Immunogenicity, Vaccine ; Licenses ; Manufacturing ; Meningococcal vaccines ; Mens health ; Mice ; Mice, Inbred BALB C ; Neisseria meningitidis ; Neisseria meningitidis, Serogroup C ; Polysaccharides, Bacterial - immunology ; Proteins ; Recombinant Proteins - chemistry ; Research centers ; Saccharides ; Serum Bactericidal Antibody Assay ; Streptococcus infections ; Streptococcus pneumoniae ; Tetanus ; Toxins ; Vaccines ; Vaccines, Conjugate - chemistry ; Vaccines, Conjugate - immunology</subject><ispartof>Vaccine, 2016-07, Vol.34 (35), p.4235-4242</ispartof><rights>2016</rights><rights>Copyright © 2016. 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subjects Allergy and Immunology
Animals
Antibodies, Bacterial - blood
Antibody Formation
Antigens
Candidates
Carrier protein
Carrier Proteins - chemistry
Chromatography
CRM197
Diphtheria
E coli
Genomes
Glucans - chemistry
Glycoconjugates
Glycoconjugates - chemistry
Haemophilus influenzae
Immunogenicity
Immunogenicity, Vaccine
Licenses
Manufacturing
Meningococcal vaccines
Mens health
Mice
Mice, Inbred BALB C
Neisseria meningitidis
Neisseria meningitidis, Serogroup C
Polysaccharides, Bacterial - immunology
Proteins
Recombinant Proteins - chemistry
Research centers
Saccharides
Serum Bactericidal Antibody Assay
Streptococcus infections
Streptococcus pneumoniae
Tetanus
Toxins
Vaccines
Vaccines, Conjugate - chemistry
Vaccines, Conjugate - immunology
title Preclinical studies on new proteins as carrier for glycoconjugate vaccines
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