Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenoviridae / genetics
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Adhesins, Bacterial / genetics
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Adhesins, Bacterial / immunology*
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Administration, Intranasal
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Animals
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Antibodies, Bacterial / blood
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Bacterial Proteins / genetics
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Bacterial Proteins / immunology*
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Female
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Genetic Vectors
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Immunoglobulin G / blood
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Lipoproteins / genetics
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Lipoproteins / immunology*
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Lung / immunology*
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Lung / microbiology
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Mice
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Mice, Inbred BALB C
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Pneumococcal Vaccines / administration & dosage
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Pneumococcal Vaccines / genetics
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Pneumococcal Vaccines / immunology*
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Pneumonia, Pneumococcal / prevention & control*
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Streptolysins / genetics
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Streptolysins / immunology*
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Vaccines, Subunit / administration & dosage
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Vaccines, Subunit / genetics
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Vaccines, Subunit / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
Substances
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Adhesins, Bacterial
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Antibodies, Bacterial
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Bacterial Proteins
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Immunoglobulin G
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Lipoproteins
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Pneumococcal Vaccines
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PsaA protein, Streptococcus
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Streptolysins
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Vaccines, Subunit
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Vaccines, Synthetic
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plY protein, Streptococcus pneumoniae
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pneumococcal surface protein A