PROTECTIVE ACTIVITY STUDY OF A CANDIDATE VACCINE AGAINST ROTAVIRUS INFECTION BASED ON RECOMBINANT PROTEIN FliCVP6VP8

Духовлинов, И. В.; Богомолова, Е. Г.; Федорова, Е А; Симбирцев, А. С.

doi:10.15789/1563-0625-2016-5-417-424

Cited by 9 publications

(1 citation statement)

References 8 publications

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“…Одна из новых парадигм заключается в создании нереплицирующихся вакцин, в том числе на основе белка VP6. В связи с этим ряд исследовательских групп как в нашей стране, так и за рубежом работают над созданием рекомбинантных конструкций [28][29][30].…”

Section: Discussionunclassified

Phylodynamic characteristics of the Russian population of rotavirus А (Reoviridae: Sedoreovirinae: Rotavirus) based on the VP6 gene

Морозова¹,

Sashina²,

Новикова³

2021

Voprosy virusologii

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Introduction. Rotavirus A is one of the leading causes of acute gastroenteritis in children in the first years of life. Rotavirus infection is currently classified as a preventable infection. The most abundant rotavirion protein is VP6.Material and methods. Phylogenetic analysis and calculation of phylodynamic characteristics were carried out for 262 nucleotide sequences of the VP6 gene of rotavirus species A, isolated in Russia, using the BEAST v.1.10.4 software package. The derivation and analysis of amino acid sequences was performed using the MEGAX program.Results. This study provides phylodynamic characteristics of the rotaviruses in Russia based on the sequences coding VP6 protein. Bayesian analysis showed the circulation of rotaviruses of three sublineages of genotype I1 and three sublineages of genotype I2 in Russia. The level of accumulation of mutations was established, which turned out to be similar for genotypes I1 and I2 and amounted to 7.732E-4 and 1.008E-3 nucleotides/site/year, respectively. The effective population sizes based on nucleotide sequences of the VP6 I1 and I2 genotypes are relatively stable while after the 2000s there is a tendency of its decreasing. Comparative analysis of the amino acid sequences in the region of the intracellular neutralization sites A (231–260 aa) and B (265–292 aa) made it possible to reveal a mutation in position V252I in a proportion of Russian strains of genotype I1 some strains of genotypes I1 and I2 had mutation I281V. These substitutions were not associated with any sublineages to which the strains belong. The analysis of three T-cell epitopes revealed four amino acid differences (in aa positions 305, 315, 342, 348) that were associated with the first or second genogroup.Conclusion. Based on the phylodynamic characteristics and amino acid composition of antigenic determinants, it was concluded that the VP6 protein is highly stable and could potentially be a good model for development of a rotavirus vaccine.

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Section: Discussionunclassified

Phylodynamic characteristics of the Russian population of rotavirus А (Reoviridae: Sedoreovirinae: Rotavirus) based on the VP6 gene

Морозова¹,

Sashina²,

Новикова³

2021

Voprosy virusologii

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Study of immunogenicity and safety of a candidate rotavirus vaccine based on a recombinant hybrid protein

Varyushina

Анатольевна²,

Alexandrov

et al. 2021

Medical academic journal

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BACKGROUND: Rotaviruses are the main cause of acute gastroenteritis in children in both developed and developing countries. Vaccination is the only way to prevent severe and fatal course of this disease. Live attenuated viruses-based vaccines currently available can have a number of side effects. A candidate rotavirus vaccine reported is based on a hybrid recombinant protein FliCVP6VP8, which includes a VP6 protein fragment, a rotavirus A VP8 protein fragment, and S. typhimurium FliC flagellin components. AIM: The aim was to evaluate the immunogenicity and safety of а preparation Rotavirus vaccine, recombinant in preclinical studies. MATERIALS AND METHODS: The immunogenicity of vaccine (blood antibody titers, antigen-specific proliferative response of spleen cells) was evaluated in BALB/c mice. The acute and subchronic toxicity, the possible irritating effect, pyrogenicity and the anaphylactic effect and delayed type hypersensitivity were evaluated in laboratory mice, rats, Guinea pigs, and rabbits. RESULTS: Double immunization of mice with the candidate vaccine demonstrated a significant increase in antibody titers in mouse sera compared to that in control mice. Evaluation of antigen-specific proliferative response after double immunization with a candidate vaccine demonstrated a significant increase in the values of stimulated proliferation. Evaluation of safety through acute and chronic toxicity studies demonstrated no toxicity. The immunostimulatory effect of vaccine was demonstrated when evaluating the number of antibody-producing cells with sheep red blood cells as antigens. The number of white blood cells was demonstrated to increase after the prolonged vaccine administration. CONCLUSIONS: The preclinical studies have demonstrated safety of the candidate rotavirus vaccine and its capability to produce the immune response.

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Rotavirus infection and immunity: discussion issues of clinical and immunological studies

Горбунов

Мазанкова

Оськин

2020

Ross. vestn. perinatol. pediatr.

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The article reflects the literature data on the immune response mechanisms to rotavirus infection. The authors note that innate immunity factors play the leading role in protecting the organism from rotavirus. They demonstrate that both cellular and humoral components of the immune system are important in the pathogenesis of rotavirus infection. The protective effect is based on the activation of interferon and other cytokines, as well as TLR – innate immune receptor for double-stranded rotavirus RNA. The authors also describe the age-related aspects of the immune response, which cause a higher susceptibility to rotavirus in the neonatal period and its reduction with age.

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PROTECTIVE ACTIVITY STUDY OF A CANDIDATE VACCINE AGAINST ROTAVIRUS INFECTION BASED ON RECOMBINANT PROTEIN FliCVP6VP8

Cited by 9 publications

References 8 publications

Phylodynamic characteristics of the Russian population of rotavirus А (Reoviridae: Sedoreovirinae: Rotavirus) based on the VP6 gene

Phylodynamic characteristics of the Russian population of rotavirus А (Reoviridae: Sedoreovirinae: Rotavirus) based on the VP6 gene

Study of immunogenicity and safety of a candidate rotavirus vaccine based on a recombinant hybrid protein

Rotavirus infection and immunity: discussion issues of clinical and immunological studies

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