Median infective dose of Treponema pallidum determined in a highly susceptible guinea pig strain

Abstract

The median infective dose of Treponema pallidum subsp. paUidum and the production of immunity to reinfection in C4D guinea pigs have been determined with 10' to 106 organisms per infective dose. The mean infective dose is 102 organisms, and immunity-in those animals that demonstrated lesions-developed after 4.5 months postinfection. The suitability of the guinea pig as an alternative model for venereal syphilis has been gradually established (11, 19). We have examined inbred strains 2 and 13, outbred strains Hartley and Albany, and a strain deficient in the fourth complement component (C4D). We have found that the C4D animals are the most susceptible to Treponema pallidum infection and develop the most severe clinical symptoms among the various strains of guinea pigs (21). Possibly because of their high susceptibility, the clinical course of T. pallidum infection in C4D animals is practically unaffected by the factors of age, sex, and site of inoculation (22). Moreover, like humans, rabbits, or inbred strain 2 guinea pigs, T. pallidum-infected C4D animals respond with production of circulating immune complexes and autoantibodies to fibronectin and creatine kinase (2). Although C4D is not strictly an inbred strain, we have demonstrated that differences in histocompatibility within the strain seem to be negligible, as indicated by mixed lymphocyte cultures and prolonged (at least up to 6 months posttransfusion) survival of cells adoptively transferred (24). This is consistent with the concept that graft-versus-host reaction is very mild or unnoticeable in guinea pigs (14). Webster et al. (15) reported the establishment of a successful allogeneic chimeric state in C4D guinea pigs (Hartley-C4D) for more than 1 year. The C4D guinea pig has also a great potential for experimental congenital syphilis (23) and for establishing a guinea pigadapted strain of T. pallidum (20). The potential usefulness of the C4D guinea pig for experimental syphilis calls for determination of the median infective dose (ID50) of T.

Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols

“…In the present studies, we used guinea pigs with high susceptibilities to T. pallidum infection (35), the recombinant antigens were purified to near homogeneity, twice as much antigen (600 versus 300 ,Lg) was used, and RIBI adjuvant enforced with CWS (MPL, TDM, and CWS) was introduced. Those factors seem to contribute to the results obtained.…”

“…In the present report, the protocol of immunization differs substantially from the previous one. TmpA, TmpB, and TmpC antigens purified to near homogeneity and incorporated into RIBI adjuvant containing CWS were administered in six injections (total of 600 ,ug of antigen) to highly susceptible (50% infective dose, 102 organisms) C4D guinea pigs (35).…”

Target organs of infection in guinea pigs with acquired congenital syphilis

“…The C4-deficient (C4D) guinea pig strain, genetically related to inbred strain 13, is very susceptible (50% infective dose ϭ 10 2 organisms), whereas the Albany (Alb) line, which is haplotype identical to inbred strain 2, is highly resistant (50% infective dose, Ͼ10 9 organisms) to cutaneous infection by T. pallidum (37,38). The genetic backgrounds and clinical and immunological responses of these two partially inbred strains compared with those of inbred strains 2 and 13 have been previously reported (34,35,37). It should be stressed that C4D animals have a health status, life span, humoral and cellular immunocompetence, and susceptibilities to infectious agents similar to those of the original, complement-sufficient strain 13 (5).…”

“…Virulent T. pallidum subsp. pallidum Nichols (VTP), freshly prepared from orchitic rabbit testes (36,37), was used to infect 10 C4D (five intradermally [i.d.] and five intravenously [i.v.])…”