A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice

• Published in: PloS one Vol. 10; no. 12; p. e0144196
• Main Authors: Alves, Joana, Madureira, Pedro, Baltazar, Maria Teresa, Barros, Leandro, Oliveira, Liliana, Dinis-Oliveira, Ricardo Jorge, Andrade, Elva Bonifácio, Ribeiro, Adília, Vieira, Luís Mira, Trieu-Cuot, Patrick, Duarte, José Alberto, Carvalho, Félix, Ferreira, Paula
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.12.2015; Public Library of Science (PLoS)
• Subjects: Adults; Animals; Animals, Newborn; Antibiotics; Antibodies, Bacterial - immunology; Antigens; Bacteria; Bacterial infections; Bacterial vaccines; Bacteriology; Biomarkers; Brain; Cloning; Cytokines - blood; Dehydrogenases; Diabetes; Diabetes mellitus; Disease Models, Animal; Female; Formulations; Genetic aspects; Geriatrics; Glyceraldehyde-3-phosphate dehydrogenase; Glyceraldehyde-3-Phosphate Dehydrogenases - immunology; Glycolysis; Health sciences; Heart; Immunization; Immunogenicity; Infections; Infectious diseases; Inflammation Mediators - blood; Legal medicine; Life Sciences; Liver; Mathematical models; Meningitis; Mice; Microbiology and Parasitology; Neonates; Newborn babies; Older people; Organs; Pathogens; Phosphates; Physiological aspects; Pregnancy; Prevention; Proteins; Serotypes; Stability analysis; Stability tests; Streptococcal infections; Streptococcal Infections - immunology; Streptococcal Infections - metabolism; Streptococcal Infections - mortality; Streptococcal Infections - prevention & control; Streptococcal Vaccines - administration & dosage; Streptococcal Vaccines - adverse effects; Streptococcal Vaccines - immunology; Streptococcus; Streptococcus agalactiae; Streptococcus agalactiae - enzymology; Streptococcus agalactiae - immunology; Streptococcus infections; Toxicity; Vaccines; Portugal
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144196

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.