We studied the immune responses of guinea pigs and humans to two Legionella pneumophila
antigens. Guinea pigs surviving a lethal intraperitoneal challenge dose of virulent L. pneumophila exhibited strong cutaneous delayed-type
hypersensitivity (DTH) reactions to purified OmpS (28-kDa major outer
membrane protein) and Hsp60 (
heat shock protein or common
antigen), while weak DTH reactions were noted for extracellular
protease (major secretory
protein [MSP] [ProA]) and no reaction was observed with an
ovalbumin (OA) control. Lymphocyte proliferation responses (LPRs) were measured for peripheral blood and spleen lymphocytes from guinea pigs surviving sublethal and lethal challenge doses of L. pneumophila. Lymphocytes from uninfected animals showed no proliferation to Hsp60 or OmpS, while lymphocytes from sublethally and lethally challenged animals exhibited strong proliferative responses to Hsp60 and OmpS. Guinea pigs vaccinated with purified OmpS exhibited low antibody titers and strong DTH and LPRs to OmpS, whereas lymphocytes from animals vaccinated with Hsp60 exhibited weak DTH responses and high antibody titers to Hsp60. All guinea pigs immunized with OmpS survived experimental challenge with L. pneumophila (two of two in a pilot study and seven of seven in trial 2) versus zero of seven OA-immunized controls (P = 0.006 by Fisher's exact test). In three
vaccine trials in which animals were vaccinated with Hsp60, only 1 guinea pig of 15 survived lethal challenge. Peripheral blood lymphocytes (PBLs) from humans with
legionellosis showed stronger LPRs to OmpS than PBLs from humans with no history of
legionellosis (P = 0.0002 by Mann-Whitney test). PBLs of humans surviving
legionellosis exhibited a lower but highly significant proliferative response to Hsp60 (P < 0.0001 compared with controls by Mann-Whitney test). These studies indicate that OmpS and Hsp60 are important
antigens associated with the development of protective cellular immunity. However, as determined in
vaccine trial studies in the guinea pig model for
legionellosis, the species-specific
antigen OmpS proved much more effective than the genus-common Hsp60
antigen.