Effective post-exposure protection against lethal orthopoxviruses infection by vaccinia immune globulin involves induction of adaptive immune response.

The therapeutic potential of human vaccinia immunoglobulin (VIG) in orthopoxvirus infection was examined using two mouse models for human poxvirus, based on Ectromelia virus and Vaccinia Western Reserve (WR) respiratory infections. Despite the relatively fast clearance of human VIG from mice circulation, a single VIG injection protected immune-competent mice against both infections. Full protection against lethal Ectromelia virus infection was achieved by VIG injection up to one day post-exposure, and even injection of VIG two or three days post-infection conferred solid protection (60-80%). Nevertheless, VIG failed to protect VACV-WR challenged immune-deficient mice, even though repeated injections prolonged SCID mice survival. These results suggest the involvement of host immunity in protection. VIG provides the initial protective time-window allowing induction of the adaptive response required to achieve complete protection. Additionally, VIG can be administered in conjunction with active Vaccinia-Lister vaccination. Vaccine efficiency is not impaired, providing a non-prohibitive VIG dose is used. Thus, VIG can be used as a prophylactic measure against post-vaccinal complications but could also serve for post-exposure treatment against smallpox.

A role for NKG2D in NK cell-mediated resistance to poxvirus disease.

Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. C57BL/6 (B6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. Previous studies have shown that natural killer (NK) cells are a component of innate immunity that is essential for the B6 mice resistance to mousepox. However, the mechanism of NK cell-mediated resistance to OPV disease remains undefined. Here we show that B6 mice resistance to mousepox requires the direct cytolytic function of NK cells, as well as their ability to boost the T cell response. Furthermore, we show that the activating receptor NKG2D is required for optimal NK cell-mediated resistance to disease and lethality. Together, our results have important implication towards the understanding of natural resistance to pathogenic viral infections.

Monoclonal antibodies specific for H-2K and H-2D antigens on cytotoxic T cells can inhibit their function.

Antibodies specific for murine major histocompatibility gene complex (MHC) class I H-2K and H-2D molecules present on cytotoxic T (Tc) cells have been shown to inhibit their function of target cell lysis. This could only be demonstrated by using a more sensitive assay for T-cell-mediated lysis, and many monoclonal antibodies of different Ig class, origin, and specificity can be shown to inhibit alloreactive as well as MHC-restricted Tc cells. These antibodies inhibit different activated T-cell populations to varying extents, and anti-H-2K but not anti-H-2D antibodies show a synergistic effect with anti-Lyt-2 antibodies. Data here suggest that MHC molecules may be located in or near the T-cell receptor complex on these cells.