Article

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

Department of Infectious Diseases, Israel Institute for Biological Research, Israel.
Vaccine (impact factor: 3.77). 03/2009; 27(11):1691-9. DOI:10.1016/j.vaccine.2009.01.038 pp.1691-9
Source: PubMed

ABSTRACT 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.

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    Article: Therapeutic Vaccines and Antibodies for Treatment of Orthopoxvirus Infections
    Xiao Yuhong, Stuart N. Isaacs
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    ABSTRACT: Despite the eradication of smallpox several decades ago, variola and monkeypox viruses still have the potential to become significant threats to public health. The current licensed live vaccinia virus-based smallpox vaccine is extremely effective as a prophylactic vaccine to prevent orthopoxvirus infections, but because of safety issues, it is no longer given as a routine vaccine to the general population. In the event of serious human orthopoxvirus infections, it is important to have treatments available for individual patients as well as their close contacts. The smallpox vaccine and vaccinia immune globulin (VIG) were used in the past as therapeutics for patients exposed to smallpox. VIG was also used in patients who were at high risk of developing complications from smallpox vaccination. Thus post-exposure vaccination and VIG treatments may again become important therapeutic modalities. This paper summarizes some of the historic use of the smallpox vaccine and immunoglobulins in the post-exposure setting in humans and reviews in detail the newer animal studies that address the use of therapeutic vaccines and immunoglobulins in orthopoxvirus infections as well as the development of new therapeutic monoclonal antibodies.
    Viruses. 01/2010;
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Keywords

active Vaccinia-Lister vaccination
 
day post-exposure
 
fast clearance
 
host immunity
 
human vaccinia immunoglobulin
 
human VIG
 
immune-competent mice
 
immune-deficient mice
 
initial protective time-window
 
lethal Ectromelia virus infection
 
mouse models
 
non-prohibitive VIG dose
 
orthopoxvirus infection
 
prophylactic measure
 
SCID mice survival
 
single VIG injection
 
therapeutic potential
 
Vaccine efficiency
 
Vaccinia Western Reserve
 
VIG injection
 

Shlomo Lustig