%0 Journal Article
%T Immunogenicity and Protective Efficacy of a Polyvalent DNA Vaccine against Human Orthopoxvirus Infections Based on Smallpox Virus Genes
%A Rinat A. Maksyutov
%A Elena V. Gavrilova
%A Galina V. Kochneva
%A Sergei N. Shchelkunov
%J Journal of Vaccines
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/618324
%X DNA vaccines combining plasmids carrying the variola virus genes M1R, A30L, and F8L of intracellular virion surface membrane proteins as well as A36R and B7R of the extracellular virus envelope proteins under control of Rous sarcoma virus or cytomegalovirus promoters have been constructed. These DNA vaccines induced production of a high titers of vaccinia virus-neutralizing antibodies in mice similar to those elicited by the live vaccinia virus immunization. Mice vaccinated by created DNA vaccine were completely protected against a lethal (10 LD50) challenge with highly pathogenic ectromelia virus. These results suggest that such vaccine should be efficient in immunization of humans against smallpox. 1. Introduction The historically first method used for human protection against devastating smallpox epidemics was the so-called variolation, that is, an intracutaneous inoculation of healthy persons with infectious material from human smallpox cases. The disease thus induced had a shorter incubation period and a milder course as compared with the disease caused by a common respiratory transmission of this infection. The mortality rate after variolation was 0.5£¿2% versus 20£¿30% typical for the smallpox epidemics. The discovery of human vaccination using first cowpox virus (CPXV) and then vaccinia virus (VACV) had led to a considerable decrease in the severe side reactions [1, 2]. Taking into account the postvaccination complications caused by classical live vaccine involving VACV and confirmation of the global smallpox eradication, the World Health Organization recommended in 1980 to stop further vaccination against this infection [1]. Subsequent worldwide cessation of the vaccination against smallpox has created a most dangerous situation when the human population year by year becomes ever more unprotected not only from a potential infection with variola virus (VARV) as a result of a bioterrorism attack or reemergence of the virus in nature, but also from infection with other closely related orthopoxviruses, the natural reservoir of which is small rodents [3¨C5]. This is demonstrated by more frequent outbreaks of human orthopoxvirus infections caused by monkeypox virus (MPXV), CPXV, and VACV [6¨C10]. The absence of efficient antivirals makes the vaccine prevention the most important specific tool for control of the orthopoxvirus infections among humans. Use of the classical live VACV vaccine for mass vaccinations is now unacceptable because of a relatively large number of potential complications, especially taking into account the increased number of
%U http://www.hindawi.com/journals/jv/2013/618324/