title: A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice.
abstract: Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases.
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Alves
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Madureira
authors.affiliation: REQUIMTE, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Baltazar
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Leandro
authors.initials: L
authors.lastname: Barros
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Liliana
authors.initials: L
authors.lastname: Oliveira
authors.affiliation: REQUIMTE, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.|Department of Legal Medicine and Forensic Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.|IINFACTS, Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, Advanced Institute of Health Sciences, North (ISCS-N), CESPU, CRL, Gandra, Portugal.
authors.forename: Ricardo Jorge
authors.initials: RJ
authors.lastname: Dinis-Oliveira
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Elva Bonifácio
authors.initials: EB
authors.lastname: Andrade
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Adília
authors.initials: A
authors.lastname: Ribeiro
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
authors.forename: Luís Mira
authors.initials: LM
authors.lastname: Vieira
authors.affiliation: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram-Positif, Centre National de la Recherche Scientifique (CNRS ERL 3526), Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trieu-Cuot
authors.affiliation: CIAFEL, Faculdade de Desporto, Universidade do Porto, Porto, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: REQUIMTE, Laboratório de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.affiliation: ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.|Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.|IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology; D015415:Biomarkers; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology*; D007114:Immunization; D018836:Inflammation Mediators / Q000097:blood; D051379:Mice; D013290:Streptococcal Infections / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000201:enzymology / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D022541:Streptococcal Vaccines; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases