Pneumococcal pneumonia and bacteremia model in mice for the analysis of protective antibodies

Pneumococci cause infection by colonizing the nasopharynx and invading the mucosal surfaces. Infection models in mice, where the natural route of infe ction is mimicked, may be useful to study antibody mediated protection agai nst pneumococcal pneumonia and bacteremia. We have established a pneumococc al pneumonia and bacteremia model in mice and investigated the protective c apacity of human antibodies. Intranasal challenge with serotypes 1, 3, 6A a nd 8 caused lung infection and bacteremia which was lethal. Serotype 6B cau sed low, but detectable, infection and other serotypes tested were not viru lent. Passive immunization with a human IgG preparation i.p. protected mice in a dose dependent manner against bacteremia caused by the virulent serot ypes (except serotype 3) and partially or completely cleared pneumococci fr om the lungs of mice infected with serotypes 1, 6A and 8. Adsorption of ant ibodies with homologous capsular polysaccharides eliminated protection agai nst disease but adsorption with cell wall polysaccharides (CWPS) did not. F urthermore, a good correlation was observed between protection of sera in v ivo and opsonic activity in vitro. The results indicate that the model may be useful to analyse the levels, isotypes, specificity and other characteri stics of human antibodies which protect against pneumococcal infection and to evaluate the protective potential of pneumococcal vaccine candidates. (C ) 2000 Academic Press.