IMMUNOPROTECTION BY MONOCLONAL-ANTIBODIES TO THE PORINS AND LIPOPOLYSACCHARIDE OF SALMONELLA-TYPHIMURIUM

Monoclonal antibodies (MAbs) were raised against the outer membrane (O M) antigens of Salmonella typhimurium. Enzyme-linked immunosorbent ass ays and Western immunoblots indicated that 10 MAbs in the panel were s pecific for surface epitopes, and 10 recognized buried epitopes of Omp C or OmpD porins; three MAbs reacted with smooth lipopolysaccharide (L PS), two bound rough LPS, and the remaining three MAbs apparently reac ted with a porin-LPS complex. We screened these MAbs and immune polycl onal sera in CAF, (lty') mice for their relative immunoprotective pote ntial against a challenge with 10 to 500 LD(50) of the virulent S. typ himurium LT-2 strain WB600, or against two LD(50) of purified OM from this organism. Polyclonal sera that contained high titers of antibodie s to porin monomers and trimers, and LPS, provided significant protect ion (33 to 100% survivors). Antiporin MAbs, when administered individu ally, did not protect or prolong the survival of mice. A mixture of MA bs with specificity for the surface, but not buried epitopes of porins , prolonged the survival of mice against endotoxemia, but none provide d significant protection against mouse typhoid. MAbs specific for smoo th (but not rough) LPS on the other hand, conferred significant protec tion against endotoxemia and mouse typhoid. Finally, MAbs that presuma bly recognized epitopes present in porin-LPS complexes, were also prot ective against endotoxemia and mouse typhoid. These results support th e role of antibodies to LPS O-chains, porin-LPS complexes, and to a le sser degree, native porins in acquired resistance to infection by S. t yphimurium. (C) 1996 Academic Press Limited.