IMMUNIZATION WITH FIMA PROTECTS AGAINST STREPTOCOCCUS-PARASANGUIS ENDOCARDITIS IN RATS

FimA, a surface-associated protein of Streptococcus parasanguis, is as sociated with initial colonization of damaged heart tissue in an endoc arditis model (D, Burnette-Curley, V, Wells, H. Viscount, C, Munro, J, Fenno, P, Fives-Taylor, and F, Macrina, Infect, Immun, 63:4669-4674, 1995), We have evaluated the efficacy of recombinant FimA as a vaccine in the rat model of endocarditis and investigated in vitro the mechan ism for the protective role of immunization, FimA-immunized and nonimm unized control animals were catheterized to induce heart valve damage and infected intravenously with 10(7) CFU of wild-type S. parasanguis FW213 bacteria, The presence of bacteria associated with platelet-fibr in vegetations 24 h postchallenge was evaluated, Immunized rats were s ignificantly less susceptible to endocarditis (2 cases among 34 animal s) than the control group (21 cases among 33 animals) (P < 0.001), Inc ubation of S, parasanguis FW213 with rabbit anti-FimA immune serum dec reased the mean percent adherence (0.34% of added cells) to platelet-f ibrin matrix in vitro compared with that of preimmune normal serum (5. 04% of added cells; P < 0.001), Adsorption of immune serum with FimA p ositive S. parasanguis FW213 yielded antiserum that failed to block ad herence to the platelet-fibrin matrix. We assessed the vaccine potenti al of FimA as a common immunogen able to provide cross-protection in s treptococcal endocarditis by determining the occurrence and expression of fimA in the viridans group streptococci and enterococci, We detect ed the presence of fimA homologs by Southern hybridization and PCR amp lification analyses and determined by immunoblotting the expression of FimA-like proteins among a variety of streptococci and enterococci th at frequently cause endocarditis. Eighty-one percent (26 of 32) of str eptococcal and enterococcal strains isolated from bacteremic patients expressed proteins that comigrated with FimA and were reactive with po lyclonal anti-FimA serum, Streptococcal DNA from strains that were pos itive by Western blot (immunoblot) analysis hybridized to the full-len gth fimA probe, Our studies suggest that FimA immunization results in antibody-mediated inhibition of bacterial adherence, a critical early event in the pathogenesis of endocarditis, Our data demonstrate that a majority of streptococcal strains associated with endocarditis have g enes that encode FimA-like proteins, Taken together, these results sug gest that FimA is a promising candidate for an endocarditis vaccine.