Antibody-independent protection in mice against type Ia group B streptococcus lethal infection

Abstract

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 potentiating natural cell-mediated immunity in the host, has not been explored. 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 anhydride) and inactivated Candida albicans (CA) cells on mouse resistance to the reference strain type Ia 090 GBS (GBS-090) lethal infection. MVE-2 and CA, respectively a synthetic and a microbial biological response modifier (BRM), are strong inducers and activators of natural resistance effectors, such as natural killer (NK) cells, macrophages and polymorphonuclear cells (PMN). The results showed that MVE-2 protected 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 days protected 100% mice when administered at 2 x 10(7) cells/mouse and when 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 specific antibodies against GBS-090 infection was excluded by the ELISA assay. Evidence exists that NK cells do not play a primary role as effectors in the MVE-2 and CA conferred protection since the strong reduction 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 kill GBS-090, but were highly effective against GBS type VI. These results seem to indicate that intracellular GBS-090 killing is a slow process requiring more than 1 h. This study demonstrates that it is possible to increase resistance to GBS-090 lethal infection by BRMs, by potentiating the antibody-independent microbicidal activity of the phagocytes.

Group B streptococci persist inside macrophages

“…In fact, a more rapid reduction in the number of intracellular GBS‐Ia and GBS‐III was observed in macrophages activated with IFN‐γ and LPS. This observation seems to be consistent with our previous in vivo data which demonstrated that immunostimulated mice were able to resist a lethal challenge with GBS‐Ia 54 . The effect of macrophage activation on GBS intracellular survival is very interesting if we consider that the phagocytic cells of neonates and preterm babies frequently have a reduced microbicidal activity 15 , 16 , 55 –57 and are therefore more susceptible to GBS infection 58…”

Effectiveness of a Simply Designed Tumor Vaccine in Prevention of Malignant Melanoma Development

“…[22][23][24][25][26] On the other hand, MVE-2 exhibits very few toxic side effects in the treated organisms. Moreover, it has also been utilized in bioconjugates, e.g.…”