Preclinical studies on new proteins as carrier for glycoconjugate vaccines.
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.
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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Tontini
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
M R
MR
Romano
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
D
D
Proietti
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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Balducci
GSK Vaccines Institute for Global Health (GVGH) S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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Micoli
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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Balocchi
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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L
Santini
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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Masignani
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy.
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F
Berti
GSK Vaccines S.r.l., Via Fiorentina 1, 53100 Siena, Italy. Electronic address: paolo.x.costantino@gsk.com.
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Costantino
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D002352:Carrier Proteins / Q000737:chemistry*; D005936:Glucans / Q000737:chemistry; D006001:Glycoconjugates / Q000737:chemistry*; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008807:Mice, Inbred BALB C; D038542:Neisseria meningitidis, Serogroup C; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry; D058248:Serum Bactericidal Antibody Assay; D018074:Vaccines, Conjugate / Q000737:chemistry* / Q000276:immunology
D000907:Antibodies, Bacterial; D002352:Carrier Proteins; D005936:Glucans; D006001:Glycoconjugates; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D018074:Vaccines, Conjugate; C008247:laminaran
CRM(197); Carrier protein; Glycoconjugates; Meningococcal vaccines