Mucosal delivery of a pneumococcal vaccine using Lactococcus lactis affords protection against respiratory infection.
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.


CONCLUSIONS
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.
Hanniffy
Sean B
SB
Institute of Food Research, Norwich Research Park, Colney, Norwich, United Kingdom.
Carter
Andrew T
AT
Hitchin
Ed
E
Wells
Jerry M
JM
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D013294:Lactococcus lactis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022242:Pneumococcal Vaccines; D014614:Vaccines, Synthetic; C051592:pneumococcal surface protein A