BACKGROUND: Economical and effective vaccines against Streptococcus pneumoniae (pneumococcus) are needed for implementation in poorer countries where the disease burden is highest. Here, we evaluated Lactococcus lactis intracellularly producing the pneumococcal surface protein A (PspA) as a mucosal vaccine in conferring protection against pneumococcal disease. METHODS: Mice were intranasally (inl) immunized with the lactococcal vaccine. Control groups were also immunized with similar amounts of recombinant PspA administered inl or subcutaneously with alum. PspA-specific antibodies in serum samples and lung lavage fluids were measured before challenge in intraperitoneal sepsis and inl respiratory-infection models of pneumococcal disease. RESULTS: The lactococcal vaccine afforded better protection against respiratory challenge with pneumococcus than did vaccination with purified antigen given inl or by injection with alum. This finding was associated with a shift toward a Th1-mediated immune response characterized by reduced antibody titers to the PspA antigen. In the sepsis model, the lactococcal vaccine afforded resistance to disease on a par with that obtained with the injected vaccine, demonstrating its efficacy against different forms of pneumococcal disease. CONCLUSION: Given the safety profile of L. lactis, there is considerable potential to develop a pneumococcal vaccine for use in humans and to broaden this approach to combat other major pathogens.
BACKGROUND: Economical and effective vaccines against Streptococcus pneumoniae (pneumococcus) are needed for implementation in poorer countries where the disease burden is highest. Here, we evaluated Lactococcus lactis intracellularly producing the pneumococcal surface protein A (PspA) as a mucosal vaccine in conferring protection against pneumococcal disease. METHODS:Mice were intranasally (inl) immunized with the lactococcal vaccine. Control groups were also immunized with similar amounts of recombinant PspA administered inl or subcutaneously with alum. PspA-specific antibodies in serum samples and lung lavage fluids were measured before challenge in intraperitoneal sepsis and inl respiratory-infection models of pneumococcal disease. RESULTS: The lactococcal vaccine afforded better protection against respiratory challenge with pneumococcus than did vaccination with purified antigen given inl or by injection with alum. This finding was associated with a shift toward a Th1-mediated immune response characterized by reduced antibody titers to the PspA antigen. In the sepsis model, the lactococcal vaccine afforded resistance to disease on a par with that obtained with the injected vaccine, demonstrating its efficacy against different forms of pneumococcal disease. CONCLUSION: Given the safety profile of L. lactis, there is considerable potential to develop a pneumococcal vaccine for use in humans and to broaden this approach to combat other major pathogens.
Authors: Bernard R Quigley; Matthew Hatkoff; David G Thanassi; Mahamoudou Ouattara; Zehava Eichenbaum; June R Scott Journal: Infect Immun Date: 2009-12-22 Impact factor: 3.441
Authors: Stephen I Pelton; Melinda M Pettigrew; Stephen J Barenkamp; Fabrice Godfroid; Carlos G Grijalva; Amanda Leach; Janak Patel; Timothy F Murphy; Sanja Selak; Lauren O Bakaletz Journal: Otolaryngol Head Neck Surg Date: 2013-04 Impact factor: 3.497
Authors: Maria Leonor S Oliveira; Eliane N Miyaji; Daniela M Ferreira; Adriana T Moreno; Patricia C D Ferreira; Fernanda A Lima; Fernanda L Santos; Maria Aparecida Sakauchi; Célia S Takata; Hisako G Higashi; Isaías Raw; Flavia S Kubrusly; Paulo L Ho Journal: PLoS One Date: 2010-05-27 Impact factor: 3.240
Authors: D M Ferreira; M Darrieux; D A Silva; L C C Leite; J M C Ferreira; P L Ho; E N Miyaji; M L S Oliveira Journal: Clin Vaccine Immunol Date: 2009-03-11