Abstract
After Edward Jenner established human vaccination over 200 years ago, attenuated poxviruses became key players to contain the deadliest virus of its own family: Variola virus (VARV), the causative agent of smallpox. Cowpox virus (CPXV) and horsepox virus (HSPV) were extensively used to this end, passaged in cattle and humans until the appearance of vaccinia virus (VACV), which was used in the final campaigns aimed to eradicate the disease, an endeavor that was accomplished by the World Health Organization (WHO) in 1980. Ever since, naturally evolved strains used for vaccination were introduced into research laboratories where VACV and other poxviruses with improved safety profiles were generated. Recombinant DNA technology along with the DNA genome features of this virus family allowed the generation of vaccines against heterologous diseases, and the specific insertion and deletion of poxvirus genes generated an even broader spectrum of modified viruses with new properties that increase their immunogenicity and safety profile as vaccine vectors. In this review, we highlight the evolution of poxvirus vaccines, from first generation to the current status, pointing out how different vaccines have emerged and approaches that are being followed up in the development of more rational vaccines against a wide range of diseases.
Highlights
The most deadly poxvirus, Variola virus (VARV), was the agent that caused smallpox, a fatal disease for which records go back more than 3500 years [1] and which is suspected to have emerged in 10,000 BCE [2]
We review how different poxviruses have evolved in nature and in controlled laboratory environments to generate a wide variety of strains that are being used as vaccine candidates against homologous diseases such as smallpox, heterologous diseases such as rabies, HIV/AIDS, hepatitis C, tuberculosis, malaria and leishmaniasis, among others, or against other complex diseases like cancer
M65 and M101 strains of vaccinia virus (VACV) were generated in the 1980s after 65 and 101 passages, respectively, of Friend erythroleukemia (FEL) cell line persistently infected with Western Reserve (WR) strain [268]
Summary
The most deadly poxvirus, VARV, was the agent that caused smallpox, a fatal disease for which records go back more than 3500 years [1] and which is suspected to have emerged in 10,000 BCE [2]. In 1798 the English physician Edward Jenner established a much safer practice, demonstrating that another poxvirus, CPXV—which infected cattle—could be used to prevent smallpox infections in humans. This procedure became known as vaccination, derived from “vacca,” the Latin word for cow. Many of the pioneers in these new sciences used VACV for their studies and vaccine production was introduced into laboratories and taken over by scientists rather than local physicians This entailed an improvement in the quality of the vaccines, the methods for the distribution and the public health infrastructure, which led to the elimination of endemic smallpox from the industrialized countries of Europe and North America by the early 1950s [8]. We describe the sequences by which different poxvirus-based vaccines evolved with time, and how genetic manipulation of the poxvirus genome led to the development of vaccine candidates with wide application against human and animal diseases
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