title: Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci.
abstract: A whole-cell killed unencapsulated pneumococcal vaccine given by the intranasal route with cholera toxin as an adjuvant was tested in two animal models. This vaccination was highly effective in preventing nasopharyngeal colonization with an encapsulated serotype 6B strain in mice and also conferred protection against illness and death in rats inoculated intrathoracically with a highly encapsulated serotype 3 strain. When the serotype 3 challenge strain was incubated in the sera of immunized rats, it was no longer virulent in an infant-rat sepsis model, indicating that the intranasal immunization elicited protective systemic antibodies. These studies suggest that killed whole-cell unencapsulated pneumococci given intranasally with an adjuvant may provide multitypic protection against capsulated pneumococci.
authors.affiliation: Divisions of Infectious Diseases, Children's Hospital, Harvard University of Public Health, Boston, Massachusetts 02115, USA. richard.malley@tch.harvard.edu
authors.forename: R
authors.initials: R
authors.lastname: Malley
authors.forename: M
authors.initials: M
authors.lastname: Lipsitch
authors.forename: A
authors.initials: A
authors.lastname: Stack
authors.forename: R
authors.initials: R
authors.lastname: Saladino
authors.forename: G
authors.initials: G
authors.lastname: Fleisher
authors.forename: S
authors.initials: S
authors.lastname: Pelton
authors.forename: C
authors.initials: C
authors.lastname: Thompson
authors.forename: D
authors.initials: D
authors.lastname: Briles
authors.forename: P
authors.initials: P
authors.lastname: Anderson
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D004195:Disease Models, Animal; D007116:Immunization, Passive / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D022242:Pneumococcal Vaccines; D002772:Cholera Toxin