HUMAN AND GUINEA-PIG IMMUNE-RESPONSES TO LEGIONELLA-PNEUMOPHILA PROTEIN ANTIGENS OMPS AND HSP60

We studied the immune responses of guinea pigs and humans to two Legio nella pneumophila antigens. Guinea pigs surviving a lethal intraperito neal challenge dose of virulent L. pneumophila exhibited strong cutane ous delayed-type hypersensitivity (DTH) reactions to purified OmpS (28 -kDa major outer membrane protein) and Hsp60 (heat shock protein or co mmon antigen), while weak DTH reactions were noted for extracellular p rotease (major secretory protein [MSP] [ProA]) and no reaction was obs erved with an ovalbumin (OA) control. Lymphocyte proliferation respons es (LPRs) were measured for peripheral blood and spleen lymphocytes fr om guinea pigs surviving sublethal and lethal challenge doses of L. pn eumophila. Lymphocytes from uninfected animals showed no proliferation to Hsp60 or OmpS, while lymphocytes from sublethally and lethally cha llenged 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 anim als vaccinated with Hsp60 exhibited weak DTH responses and high antibo dy titers to Hsp60. All guinea pigs immunized with OmpS survived exper imental 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 l ethal 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 significa nt 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 cellu lar immunity. However, as determined in vaccine trial studies in the g uinea pig model for legionellosis, the species-specific antigen OmpS p roved much more effective than the genus-common Hsp60 antigen.