Abstract
The increasing frequency of monkeypox virus infections, new outbreaks of other zoonotic orthopoxviruses and concern about the re-emergence of smallpox have prompted research into developing antiviral drugs and better vaccines against these viruses. This article considers the genetic engineering of vaccinia virus (VACV) to enhance vaccine immunogenicity and safety. The virulence, immunogenicity and protective efficacy of VACV strains engineered to lack specific immunomodulatory or host range proteins are described. The ultimate goal is to develop safer and more immunogenic VACV vaccines that induce long-lasting immunological memory.
Highlights
The development of vaccines and subsequent widespread vaccination has resulted in the eradication of two virus diseases, smallpox [1] and rinderpest [2], the control of several others and, together with other factors such as improved hygiene, has led to improved animal welfare and an increase in human life expectancy
Cases of human monkeypox have increased in Democratic Republic of the Congo (DRC) over the last 30 years and one contributory factor is the increasing proportion of the population that is immunologically naïve to orthopoxviruses following cessation of smallpox vaccination [34]. Another factor that enhances the likelihood of orthopoxvirus infections in humans is the human immunodeficiency virus (HIV) epidemic and the consequential acquired immune deficiency syndrome (AIDS)
vaccinia virus (VACV) encodes dozens of proteins that affect the outcome of infection in vivo, we focus primarily on studies that tested the protective efficacy of VACV mutants lacking specific immunomodulators against an orthopoxvirus challenge in the appropriate animal model
Summary
The development of vaccines and subsequent widespread vaccination has resulted in the eradication of two virus diseases, smallpox [1] and rinderpest [2], the control of several others and, together with other factors such as improved hygiene, has led to improved animal welfare and an increase in human life expectancy. There have been serious outbreaks of measles in several countries including USA (Minnesota, 2017) [5], England and Wales (more than 2000 cases in 2012 and the highest level for 2 decades) [6,7,8], other parts of Europe [9] and Latin America [10] This highlights the importance of maintaining vaccination to prevent the dissemination of infectious diseases. An ancient strategy to prevent smallpox was “variolation” or “inoculation” that consisted of the deliberate infection of people, usually in the arm, with infectious material taken from pustules from a prior case of smallpox This practice was introduced into Europe by Mary Wortley Montagu, who observed this practice among the Turks in Constantinople in 1717. Most important there was widespread enthusiasm and drive to see the job completed
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