Vaccine induced immunity to schistosoma mansoni spleen cell proliferative responses before and after challenge in BALB/c mice given irradiated or normal schistosomula

ABSTRACT

Spleen cell proliferative responses in BALB/c mice were assessed at varying intervals after vaccination or primary infection and subsequent cercarial challenge. Mice were vaccinated with 500 50-Kradirradiated Schistosoma mansoni Schistosomula or infected with 20 normal schistosomula. Prior to challenge, splenic responses in the two test groups to phytohemagglutinin [PHA] declined progressively while schistosomula [SMA]-driven responses increased. After challenge, PHA responses increased in both groups on day 3 then declined to significantly lower levels compared to normal controls. On day 3 after challenge, SMA responses in vaccinated mice were vigorous, and greater than twice the responses in infected mice. Thereafter, responses in vaccinated mice declined while responses in infected mice increased on days 7 through 25 but dropped markedly by day 39. For the infected group, in vitro depletion of plastic adherent cells or Lyt 2.2[+] lymphocytes resulted in augmented SMA responses 3 days post-challenge by > 400% and > 100%, respectively. Depletion of either cell population in the vaccinated group had no significant effect. Protection assessed by total worm burdens showed a reduction of 62% in vaccinated mice and 43% reduction in infected mice. The post-challenge results indicate that these two models of anti-schistosomula immunity differed in the dynamics of their splenocyte antigen-specific proliferative responses. These findings may contribute to an understanding of the mechanisms by which resistance to S. mansoni is induced. Laboratory animals with patent Schistosoma mansoni infections are partially resistant to reinfection. This observation led to the concept of "concomitant immunity" [Smithers and Terry, 1967, 1969] which has subsequently been experimentally verified [Sher et al., 1974]. Partial protective immunity can also be induced in mice by vaccination with radiation-attenuated infectious S. mansoni larval forms [Bickle et al., 1979; Murrell et al., 1979; Dean, 1983]. Although both cellular and humoral factors have been implicated in the immunoprotective process, the exact mechanisms remain to be elucidated. Specific anti-schistosomula antibodies from chronically infected mice [Sher et al., 1977] and monoclonal antibodies raised against schistosomula antigens [Smith et al., 1982; Zodda and Phillips, 1982; Gryzch et al., 1984; Ham et al., 1984] have been shown to passively protect mice or rats against challenge infections. However, other studies have yielded conflicting data [Maddison and Kagan, 1979; Harrison et al., 1982; Bickle et al., 1985]. Spleen or lymph node cells from infected mice were not protective when transferred alone [Harrison et al., 1982] nor was protection conferred to normal partners in parabiotic pairs of normal and infected mice [Dean et al., 1981]. The role of eosinophils in the elimination of a secondary S. mansoni infection challenge was suggested on the basis of in vitro eosinophil-mediated parasite killing [Phillips and Colley, 1978] and an increase in the challenge worm burdens in mice treated with rabbits anti-mouse eosinophil serum [Mahmoud et al., 1975]. Protective mechanisms in mice vaccinated with irradiated cercariae depend on the presence of both T and B lymphoytes as evidenced by the inhability of T-cell deficient or B-cell deprived vaccinated mice to reject chollenge infections [Sher et al., 1982]. Likwise; lymphoproliferative activity, lymphokine production and antibodies against S. mansoni schistosomula are all elevated 1- 2 weeks after vaccination of mice [James et al, 1981]. IgG antibodies from mice vaccinated with irradiated cercariae confer significant passive protection against a challenge infection [Mangold and Dean, 1986]. In addition, the success in transferring protective immunity from vaccinated [resistant] mice to normal partners in parabiosis provides evidence for cellular and/or humoral protective mechanisms [Dean et al., 1981]. The present study was designed to compare the kinetics and mechanisms of splenic lymphocyte responses after primary inoculation with rormal schistosimula or vaccination with radiation-attenuated schistosomula and subsequent homologous challenge. The expected thymus dependent granulomatous response to S. mansoni eggs deposited in the tissues of mice in the former model [Boros, 1986] is apparently lacking in the latter. Differences in the cellular responsiveness between the two experimental groups, which may account for or reflect differences in the immunological mechanisms associated with protection in these two models of acquired schistosomal resistance are reported