Vaccination against Legionella pneumophila: serum antibody correlates with protection induced by heat-killed or acetone-killed cells against intraperitoneal but not aerosol infection in guinea pigs

Abstract

An aerosol model of Legionella infection has been established in guinea pigs. Infected animals showed growth of Legionella in their lungs, dissemination of organisms to the spleen, development of pneumonia and fever, and weight loss. Vaccination studies using heat-killed or acetone-killed cells were carried out, and guinea pigs were challenged intraperitoneally or by using the aerosol model of infection. Both vaccines were shown to give moderately high levels of protection against intraperitoneal challenge (28 to 145 50% lethal doses). Protection was found to be dose dependent and correlated with antibody levels as measured by enzyme-linked immunosorbent assay to an outer membrane antigen and by indirect immunofluorescence to heat-killed cells. In contrast, the same vaccination regimens that protected against intraperitoneal challenge failed to protect guinea pigs against aerosol challenge with comparable doses of Legionella, despite the presence of serum antibody. The results are discussed in terms of the possible requirements for immunity to aerosolized Legionella, including secretory immunoglobulin or cell-mediated immunity.

Guinea pigs sublethally infected with aerosolized Legionella pneumophila develop humoral and cell-mediated immune responses and are protected against lethal aerosol challenge. A model for studying host defense against lung infections caused by intracellular pathogens.

“…We have demonstrated that sublethal infection with L. pneumophila produced protective immunity in vivo against this intracellular pathogen. Moreover, we have demonstrated that sublethal infection with L. pneumophila by the airborne route, the natural route of infection, protects against lethal challenge by this Previous studies have failed to demonstrate protective immunity to L. pneumophila in vivo (12,13). We believe this is because the challenge doses in those studies were so high that they overwhelmed the capacity of the immune system to counteract the challenge.…”

“…(12), sublethally infected guinea pigs were challenged with 10 times the LD5o and not protected. In the study by Eisenstein et al (13), guinea pigs surviving a previous infection were challenged with 44 times the LD5o and were not protected.…”

Legionnaires disease: historical perspective.

“…It is unclear whether humans who have had Legionnaires disease are then immune to reinfection. Guinea pigs that have been immunized with killed L. pneumophila antigen are protected against subsequent intraperitoneal challenge, but not against aerosol infection (79). Surprisingly, Baskerville and co-workers were unable to protect guinea pigs that had been previously infected by aerosol against subsequent inhalation of a bacterial aerosol (10); in fact, the previously infected animals died somewhat sooner than their naive counterparts.…”

Sequence Analysis of the mip Gene of the Soilborne Pathogen Legionella longbeachae

“…L. pneumophila serogroup 1 and strain A5H5 were both virulent by this model and caused death in 3 of 5 animals tested. Examination of the lungs taken from a guinea pig that died due to exposure to A5H5 revealed that the air spaces of the lung parenchyma were filled with a dense cellular infiltrate consisting of neutrophils and monocyte cells, and the histological appearance was consistent with a severe acute pneumonia similar to that seen with L. pneumophila serogroup 1 (3,4,15). Animals exposed to aerosols of L. longbeachae serogroup 1 ATCC 33462 and L. longbeachae serogroup 2 ATCC 33484 developed no symptoms and were avirulent, although the numbers of Legionella organisms retained in the lung with each test strain were comparable (Table 3).…”