ANTIBODY-INDEPENDENT PROTECTION IN MICE AGAINST TYPE IA GROUP-B STREPTOCOCCUS LETHAL INFECTION

There is ample evidence that protection against group B streptococcal (GBS) disease, both in experimental animals and in humans, is related to the presence of specific antibodies and complement. However, until now the possibility of increasing resistance to GBS infection by poten tiating natural cell-mediated immunity in the host, has not been explo red. In this study we examine the effect of administering in vivo MVE- 2 (a polymer fraction of 1,2-co-polymer of divinyl ether and maleic an hydride) and inactivated Candida albicans (CA) cells on mouse resistan ce to the reference strain type Ia 090 GBS (GBS-090) lethal infection. MVE-2 and CA, respectively a synthetic and a microbial biological res ponse modifier (BRM), are strong inducers and activators of natural re sistance effecters, such as natural killer (NK) cells, macrophages and polymorphonuclear cells (PMN). The results showed that MVE-2 protecte d 100% CD-1 mice from a systemic lethal challenge with GBS-090 (5 x 10 (3) microorganisms/mouse) when administered 3 days before infection at dose of 50 mg kg(-1). CA treatment, in five doses (CA-5d) over 14 day s protected 100% mice when administered at 2 x 10(7) cells/mouse and w hen the last CA injection was given 1 day before the GBS-090 challenge . Instead, when the GBS-090 challenge was performed by intraperitoneal route, protection was obtained with CA-5d treatment but not with MVE- 2 The possibility that MVE-2 or CA stimulated a rapid production of sp ecific antibodies against GBS-090 infection was excluded by the ELISA assay. Evidence exists that NK cells do not play a primary role as eff ecters in the MVE-2 and CA conferred protection since the strong reduc tion in NK activity, due to in vivo administration of anti-asialo GM1 antibodies before GBS-090 infection, did not influence the BRM-induced protection. Besides, high NK activity levels, induced by in vivo rhIL -2 administration, did not protect the mice against GBS-090 infection. Both studies on in vivo clearance and in vitro microbicidal activity, showed that after 1 h, immunopotentiated effectors were unable to kil l GBS-090, but were highly effective against GBS type VI. These result s seem to indicate that intracellular GBS-090 killing is a slow proces s requiring more than 1 h. This study demonstrates that it is possible to increase resistance to GBS-090 lethal infection by BRMs, by potent iating the antibody-independent microbicidal activity of the phagocyte s.