Modulating Vaccinia Virus Immunomodulators to Improve Immunological Memory

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.

Deletion of Vaccinia Virus A40R Gene Improves the Immunogenicity of the HIV-1 Vaccine Candidate MVA-B

“…Among the different approaches developed to enhance the immune response induced by poxvirus vectors, one promising strategy is the removal of the VACV genes that antagonize the immune system, as the virus genome still contains several genes that interfere with host immune responses [39,40]. Several recombinant MVA vectors expressing HIV-1 antigens and containing deletions in different immunomodulatory VACV genes have been generated, and have been shown to be able to enhance immune responses to HIV-1 antigens in animal models [18,20,21,23,[69][70][71].…”

Removal of the C6 vaccinia virus interferon-β inhibitor in the hepatitis C vaccine candidate MVA-HCV elicited in mice high immunogenicity in spite of reduced host gene expression

“…However, efforts to understand the HCV-specific immune responses elicited by MVA-HCV are needed in order to improve this vaccine candidate. Firstly, despite of its attenuated phenotype, MVA still encodes for proteins that can interfere with host immune responses to viral infection (36–38), and it is described that deletion of VACV immunomodulatory genes can enhance its immunogenicity (20). Secondly, IFN-based therapy in combination with ribavirin has been the treatment of first choice despite its well-known side effects, and even in the era of new DAA therapy, treatment with IFN results in improvement of response rates and higher sustained virological response in genotypes 1 (39, 40), 2 and 3 (41, 42).…”

Genes that control vaccinia virus immunogenicity

“…Известно, что антительный ответ на противооспенную вакцинацию играет решающую роль в защите от последующей вирусной инфекции [8,9,20]. Показано, что при вируснейтрализующем титре антител в сыворотке крови вакцинированных людей от 1:32 и выше обеспечивается надежная защита от оспенной инфекции [21].…”

“…Такое разнообразие генов вирулентности, с одной стороны, позволяет создавать различные варианты аттенуированных VACV, с другой стороны, увеличивает неопределенность в получении наиболее эффективной и безопасной вакцины. Для каждого получаемого нового варианта VACV необходимо проводить многочисленные эксперименты на лабораторных животных [9].…”

“…К таким моделям относятся инфицирование мышей вирусами оспы мышей (эктромелии, ECTV) или VACV, кроликов -вирусом оспы кроликов (RPXV) или VACV, обезьян -вирусом оспы обезьян (MPXV) и др. Общие закономерности развития специфического иммунного ответа изучают также при противооспенной вакцинации добровольцев вирусом VACV [7][8][9].…”