A live avirulent mutant Legionella pneumophila vaccine induces protective immunity against lethal aerosol challenge.

Abstract

IntroductionWe have examined the capacity of a live avirulent mutant form of the intracellular bacterial pathogen Legionella pneumophila to induce immune responses and protective immunity in guinea pigs. The mutant L. pneumophila is nonlethal to guinea pigs and does not revert to virulence with passage through guinea pigs. In contrast, exposure of guinea pigs to aerosols containing wild-type L. pneumophila induces a pneumonic illness that clinically and pathologically resembles Legionnaires' disease in humans. Guinea pigs immunized by aerosol exposure to mutant L. pneumophila developed a strong humoral immune response to wild-type L. pneumophila antigens with reciprocal antibody titers of 32-512 (median 256) by the indirect fluorescent antibody assay, compared with titers of < 2 for control (sham immunized) guinea pigs. Mutant immunized but not control guinea pigs also developed strong cell-mediated immune responses to wild-type L. pneumophila antigens, as demonstrated in assays of cutaneous delayed-type hypersensitivity and in vitro splenic lymphocyte proliferation.Mutant immunized guinea pigs developed strong protective immunity to lethal aerosol challenge with wild-type L. pneumophila. In four independent experiments 40-83% of mutant immunized guinea pigs survived compared with 0% of control guinea pigs. Overall, 13 of 21 (62%) mutant immunized guinea pigs survived compared with 0 of 21 (0%) control guinea pigs (P = 0.00002, Fisher's exact test, two-tailed). Mutant immunization induced protection comparable to wild-type immunization in these studies; 8 of 14 (57%) guinea pigs immunized by wild-type L. pneumophila survived.This study demonstrates that guinea pigs immunized with a live avirulent mutant L. pneumophila vaccine (a) develop a strong humoral immune response to wild-type L. pneumophila antigens; (b) develop a strong cell-mediated immune response to wild-type L. pneumophila antigens; and (c) develop protective immunity to lethal aerosol challenge with wild-type L. pneumophila. This study demonstrates the feasibility of a vaccine against Legionnaires' disease.

Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease.

“…Male Hartley strain guinea pigs weighing 250-300 g (Simonson Laboratories, Gilroy, CA), were cared for as previously described ( 18). They were observed in the vivarium for 1 wk before challenge with L. pneumophila to ensure that they were healthy.…”

Vaccination with Legionella pneumophila membranes induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease. Protective immunity independent of the major secretory protein of Legionella pneumophila.

“…Previous studies from this laboratory have demonstrated that guinea pigs immunized with a sublethal aerosolized dose of wild-type L. pneumophila, or with an aerosolized dose of an avirulent mutant L. pneumophila develop humoral and cellmediated immune responses to wild-type L. pneumophila antigens, and protective immunity against lethal aerosol challenge with wild-type L. pneumophila (15,16). To identify immunoprotective antigens of L. pneumophila, we have focused our attention on native antigens recognized by the lymphocytes of such immune guinea pigs.…”

“…To identify immunoprotective antigens of L. pneumophila, we have focused our attention on native antigens recognized by the lymphocytes of such immune guinea pigs. Previous studies have identified two such antigenic preparations: the major secretory protein (MSP)1 of L. pneumophila and L. pneumophila membranes (16,17).…”

Legionella, légionellose

“…L'antigène détecté est un composant du LPS de la paroi cellulaire de L. pneumophila. En moyenne, la valeur prédictive positive des version [27], mais également par le succès des vaccinations dans des modèles animaux [28]. Il y a production de lymphocytes B mémoires et d'anticorps dont le rôle protecteur a été démontré au cours des réin-fections [29].…”