Vaccinia virus vaccines: Past, present and future

Abstract

Vaccinia virus (VACV) has been used more extensively for human immunization than any other vaccine. For almost two centuries, VACV was employed to provide cross-protection against variola virus, the causative agent of smallpox, until the disease was eradicated in the late 1970s. Since that time, continued research on VACV has produced a number of modified vaccines with improved safety profiles. Attenuation has been achieved through several strategies, including sequential passage in an alternative host, deletion of specific genes or genetic engineering of viral genes encoding immunomodulatory proteins. Some highly attenuated third-and fourth-generation VACV vaccines are now being considered for stockpiling against a possible re-introduction of smallpox through bioterrorism. Researchers have also taken advantage of the ability of the VACV genome to accommodate additional genetic material to produce novel vaccines against a wide variety of infectious agents, including a recombinant VACV encoding the rabies virus glycoprotein that is administered orally to wild animals. This review provides an in-depth examination of these successive generations of VACV vaccines, focusing on how the understanding of poxviral replication and viral gene function permits the deliberate modification of VACV immunogenicity and virulence.

CD4+T Cell Help Is Dispensable for Protective CD8+T Cell Memory against Mousepox Virus following Vaccinia Virus Immunization

“…Thus, VACV remains as the gold standard of a highly effective vaccine, and VACV recombinants are currently being tested as vaccines for other infectious diseases and cancer (3,4). In addition to preventing smallpox, VACV is also effective as a vaccine against lethal mousepox, a disease caused by the mousespecific OPV ectromelia virus (ECTV) (5)(6)(7)(8)(9). Hence, VACV and ECTV can be paired as a unique model to understand the mechanisms of highly effective vaccination that is likely translatable to humans.…”

Evolution of and Evolutionary Relationships between Extant Vaccinia Virus Strains

“…During the period when VACV was being grown and distributed for use as a smallpox vaccine, it acquired many different names that reflect the country or health agency involved in its propagation (9). In many cases, these viruses became linked to geographical regions.…”

“…A Russian strain, EM-63, was also (probably) derived from NYCBH by a circuitous route. Europe used many different strains, including Lister, Bern, Paris, Copenhagen, Tashkent, and Ankara, while the TianTan and Ikeda strains were used in China and Japan, respectively (9). Interestingly, viruses related to VACV continue to evolve in wild habitats, including South American cattle (10) and Southeast Asian water buffalo (11).…”

Live Antivariolic Vaccines

“…современные биотехнологические методы генетической инженерии позволяют получать новые более аттенуированные и эффективные ортопоксви-русные вакцины путем направленного введения деле-ций и/или вставок в целевые участки днк вов [20]. получение аттенуированного вируса может быть достигнуто нарушением генов, контролирующих защитные реакции организма против вирусной ин-фекции, генов круга хозяев и генов, участвующих в метаболизме нуклеиновых кислот: белки, связы-вающие и нейтрализующие интерферон, цитокины и хемокины; белки, ингибирующие апоптоз, или сиг-нальные пути, необходимые для продукции интер-ферона и других цитокинов [43].…”