Highly immunogenic variant of attenuated vaccinia virus

Yakubitskyi, S N; Колосова, И. В.; Щелкунов, С. Н.

doi:10.1134/s1607672916010105

Cited by 20 publications

(32 citation statements)

References 11 publications

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“…As shown in our previous studies, triple immunization with a polyvalent DNA vaccine or double immunization with the VACΔ6 strain provides 100% protection to mice subsequently infected with ECTV at a dose of 10 LD 50 /mouse [10, 12]. For this reason, a significantly higher resolving dose of ECTV was used, 150 LD 50 / mouse, in order to assess the differences in the effectiveness of the used immunization protocols.…”

Section: Resultsmentioning

confidence: 99%

Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections

2017

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The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VACΔ6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VACΔ6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice. The present work was aimed at comparing the immunity to smallpox generated by various immunization protocols using the DNA vaccine and VACΔ6. It has been established that immunization of mice with a polyvalent DNA vaccine, followed by boosting with recombinant VACΔ6, as well as double immunization with VACΔ6, induces production of VACV-neutralizing antibodies and provides protection to mice against a 150 LD50 dose of ECTV. The proposed immunization protocols can be used to develop safe vaccination strategies against smallpox and other human orthopoxvirus infections.

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Section: Resultsmentioning

confidence: 99%

Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections

2017

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“…Многочисленные работы, посвященные делеции (удалению) генов иммуномодулирующих факторов VACV, позволили выявить некоторые вирусные гены, инактивация которых наряду с аттенуацией вируса приводит к увеличению его иммуногенности [43][44][45][46][47][48][49][50][51][52][53]. Как видим из данных, приведенных в табл.…”

Section: увеличение иммуногенности аттенуированной противооспенной ваunclassified

Genes that control vaccinia virus immunogenicity

Shchelkunov

Shchelkunova

2020

Acta Naturae

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The live smallpox vaccine was a historical first and highly effective vaccine. However, along with high immunogenicity, the vaccinia virus (VACV) caused serious side effects in vaccinees, sometimes with lethal outcomes. Therefore, after global eradication of smallpox, VACV vaccination was stopped. For this reason, most of the human population worldwide lacks specific immunity against not only smallpox, but also other zoonotic orthopoxviruses. Outbreaks of diseases caused by these viruses have increasingly occurred in humans on different continents. However, use of the classical live VACV vaccine for prevention against these diseases is unacceptable because of potential serious side effects, especially in individuals with suppressed immunity or immunodeficiency (e.g., HIV-infected patients). Therefore, highly attenuated VACV variants that preserve their immunogenicity are needed. This review discusses current ideas about the development of a humoral and cellular immune response to orthopoxvirus infection/vaccination and describes genetic engineering approaches that could be utilized to generate safe and highly immunogenic live VACV vaccines.

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“…Additional targeted deletion introduced into the A35R gene yielded another highly immunogenic attenuated strain, VACdelta6 [81], which is currently under preclinical trials as a fourth-generation smallpox vaccine candidate. This vaccine can be used in combination with the smallpox DNA vaccine [82].…”

Section: Modern Anti-smallpox Vaccinesmentioning

confidence: 99%

40 Years without Smallpox

Shchelkunova

Shchelkunov

2017

Acta Naturae

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The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

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Highly immunogenic variant of attenuated vaccinia virus

Cited by 20 publications

References 11 publications

Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections

Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections

Genes that control vaccinia virus immunogenicity

40 Years without Smallpox

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