Mucosal vaccination with a multicomponent adenovirus-vectored vaccine protects against Streptococcus pneumoniae infection in the lung.
Streptococcus pneumoniae is a major bacterial respiratory pathogen. Current licensed pneumococcal polysaccharide and polysaccharide-protein conjugate vaccines are administered by an intramuscular injection. In order to develop a new-generation vaccine that can be administered in a needle-free mucosal manner, we have constructed early 1 and 3 gene regions (E1/E3) deleted, replication-defective adenoviral vectors encoding pneumococcal surface antigen A (PsaA), the N-fragment of pneumococcal surface protein A (N-PspA), and the detoxified mutant pneumolysin (PdB) from S. pneumoniae strain D39. Intranasal vaccination with the three adenoviral vectors (Ad/PsaA, Ad/N-PspA, and Ad/PdB) in mice resulted in robust antigen-specific serum immunoglobulin G responses, as demonstrated by an enzyme-linked immunosorbent assay. In addition, nasal mucosal vaccination with the combination of the three adenoviral vectors conferred protection against S. pneumoniae strain D39 colonization in mouse lungs. Taken together, these data demonstrate the feasibility of developing a mucosal vaccine against S. pneumoniae using recombinant adenoviruses for antigen delivery.
Arévalo
Maria T
MT
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Xu
Qingfu
Q
Paton
James C
JC
Hollingshead
Susan K
SK
Pichichero
Michael E
ME
Briles
David E
DE
Girgis
Natasha
N
Zeng
Mingtao
M
D000256:Adenoviridae / Q000235:genetics; D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control*; D013301:Streptolysins / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; C085000:PsaA protein, Streptococcus; D013301:Streptolysins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C032290:plY protein, Streptococcus pneumoniae; C051592:pneumococcal surface protein A