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Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine.

ABSTRACT: Group B Streptococcus (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineering strategy, we generated strains of Escherichia coli that recombinantly express the type Ia, type Ib, and type III GBS capsular polysaccharides. We then combined the type Ia-, Ib-, and III-capsule-expressing E. coli strains with an engineered Pseudomonas aeruginosa exotoxin A (EPA) carrier protein and the PglS oligosaccharyltransferase. Coexpression of a GBS capsule, the engineered EPA protein, and PglS enabled the covalent attachment of the target GBS capsule to an engineered serine residue on EPA, all within the periplasm of E. coli. GBS bioconjugates were purified, analytically characterized, and evaluated for immunogenicity and functional antibody responses. This proof-of-concept study signifies the first step in the development of a next-generation multivalent GBS bioconjugate vaccine, which was validated by the production of conjugates that are able to elicit functional antibodies directed against the GBS capsule.

SUBMITTER: Duke JA

PROVIDER: S-EPMC8793035 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Development and Immunogenicity of a Prototype Multivalent Group B <i>Streptococcus</i> Bioconjugate Vaccine.

Duke Jeremy A JA Paschall Amy V AV Robinson Lloyd S LS Knoot Cory J CJ Vinogradov Evgeny E Scott Nichollas E NE Feldman Mario F MF Avci Fikri Y FY Harding Christian M CM

ACS infectious diseases 20211011 11

Group B <i>Streptococcus</i> (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineeri ...[more]

PMID: 34633812

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Project description:BackgroundGroup A streptococcus (GAS) is a serious human pathogen that affects people of different ages and socio-economic levels. Although vaccination is potentially one of the most effective methods to control GAS infection and its sequelae, few prototype vaccines have been investigated in humans. In this study, we report the safety and immunogenicity of a novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to healthy adults.MethodsA randomized, double-blinded, controlled Phase I clinical trial was conducted in 10 healthy adult participants. Participants were randomized 4:1 to receive the vaccine candidate (N = 8) or placebo (N = 2). A single dose of the vaccine candidate (MJ8VAX), contained 50 μg of peptide conjugate (J8-DT) adsorbed onto aluminium hydroxide and re-suspended in PBS in a total volume of 0.5 mL. Safety of the vaccine candidate was assessed by monitoring local and systemic adverse reactions following intramuscular administration. The immunogenicity of the vaccine was assessed by measuring the levels of peptide (anti-J8) and toxoid carrier (anti-DT)-specific antibodies in serum samples.ResultsNo serious adverse events were reported over 12 months of study. A total of 13 adverse events (AEs) were recorded, two of which were assessed to be associated with the vaccine. Both were mild in severity. No local reactogenicity was recorded in any of the participants. MJ8VAX was shown to be immunogenic, with increase in vaccine-specific antibodies in the participants who received the vaccine. The maximum level of vaccine-specific antibodies was detected at 28 days post immunization. The level of these antibodies decreased with time during follow-up. Participants who received the vaccine also had a corresponding increase in anti-DT serum antibodies.ConclusionsIntramuscular administration of MJ8VAX was demonstrated to be safe and immunogenic. The presence of DT in the vaccine formulation resulted in a boost in the level of anti-DT antibodies.Trial registrationACTRN12613000030774.

Dataset Information

Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine.

Publications

Development and Immunogenicity of a Prototype Multivalent Group B <i>Streptococcus</i> Bioconjugate Vaccine.

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