scholarly journals Immunogenicity of Modern Vaccine Viruses of Influenza A (H1N1)pdm09 According to Graphical Analysis

2017 ◽  
Vol 16 (5) ◽  
pp. 28-32
Author(s):  
V. S. Vakin ◽  
O. S. Konshina ◽  
E. M. Wojciechowska ◽  
E. V. Kuznetsova ◽  
V. G. Mayorova ◽  
...  

Antiepidemic measures were limited effectiveness for several years Objectives of this research were formulated as an assessment of the immunogenicity activity of the influenza virus A(H1N1)pdm09 in the composition of modern trivaccines Immunogenicity of the influenza virus A(H1N1)pdm09 in the vaccinated by vaccine was assessed by graphing, reflecting the dynamics of the multiplicity growth of antibodies (MG) and medium ratio of antibodies increasing (MR) in sera for several groups vaccinated. For comparison of vaccinated immunity was determined by traditional methods of evaluation of the immune response. As a result of the research, differences in the immunogenicity activity of the virus were revealed, which are reflected in antibody titers and the multiplicities of their growth from 2 to 4 - 8 times with the applying of similar quality vaccines. These changes couldn’t be observed with accounting study of the immune response. When immunized with a vaccine with an antigen dose of 5 mg HA identified a group of«silent» volunteers (8%) who did not respond to promotion with antigen A(H1N1)pdm09. Increasing dose of the influenza virus A(H1N1)pdm09 to 15 mg/dose in the split vaccine were result of the elimination of the group of«silent» volunteers. Simultaneously was observed a significant increase in the immune response in serum titers (up to 32-fold) and antibody growth rates Accordingly, using of the graphical form of accounting made it possible to better assess the details of the formation of collective immunity to the virus A(H1N1)pdm09 and the nature of its deviations in a number of cases.

2020 ◽  
Vol 20 (2) ◽  
pp. 33-44
Author(s):  
Andrei G. Aleksandrov ◽  
Tatiana N. Savateeva-Lyubimova ◽  
Kira I. Stosman ◽  
Arman A. Muzhikyan ◽  
Konstantin V. Sivak

Background. Acute lung injury is one of severe course of influenza infection with mortality up to 40% of patients, despite on etiological and pathogenetic therapy. The aim of the article to study of the effects of aminoguanidine on correcting on acute lung injury induced by influenza virus A/California/7/09MA (mouse-adapted) (H1N1)pdm09, collection Smorodintsev Research Institute of Influenza. Materials and methods. The study was performed on 95 outbred female mice. The mouse-adapted pandemic influenza virus A/California/7/09MA (H1N1)pdm09 was used for modeling viral infection at a dose of 1 LD50. The mortality was analysed. Levels of advanced glycation end-products (AGEs), proinflammatory cytokines in lung; saturation index and leukocytes marker parameters in blood; pathological and histological studies of lung were performed on 4 and 7 days post infection. Results. Aminoguanidine led to 2-fold decrease in mortality in mice with virus-induced acute lung injury; significantly suppressed the growth of AGEs and proinflammatory cytokine levels in lung; reduced decrease of saturation index and hematological inflammatory markers; decreased level of inflammatory injury in lung tissue. Conclusion. Aminoguanidine relieved virus-induced acute lung injury in mice. These AGEs inhibitor reduced the proinflammatory response and structural changes in respiratory tract epithelial cells induced by reactive carbonyl compounds on cell membrane.


2020 ◽  
Vol 22 (2) ◽  
pp. 357-370
Author(s):  
M. A Shuklina ◽  
L. A Stepanova ◽  
A. A. Kovaleva ◽  
A. V. Korotkov ◽  
A. A. Shaldzhyan ◽  
...  

Development of vaccines with a broad-spectrum of protection is one of the priorities in the programs of influenza prevention. Recently, the conserved fragments of influenza virus proteins (M1, M2, NP, the second subunit of the hemagglutinin HA2) provoke interest of investigators as the object of the development a broad-spectrum vaccines. Low immunogenicity present a problem when developing vaccines based on such conserved fragments. However, fusion of low immunogenic antigens into the high immunogenic carrier protein may significantly enhance their immunogenicity. The candidate vaccine protein Flg-HA2-2-4M2e was developed which containins two highly conserved viral antigens (the ectodomain of the M2 protein (M2e), 76130 region of the second subunit of HA2), fused with flagellin as a carrier protein. Flagellin (bacterial flagella protein) is a natural ligand of TLR-5, and has a strong adjuvant activity at different ways of its administration. The purpose of this study was to assess development of humoral and T cell immune response, along with broad-spectrum protection after mice immunization with the candidate Flg-HA2-2-4M2e vaccine protein. Mice were immunized intranasally three times with two-week intervals. Two weeks after the final immunization, the mice were challenged at the 5 LD50 dose with influenza viruses A/California/07/09 (H1N1) pdm09 (phylogenetic group I), or A/Shanghai/2/2013 (H7N9) (phylogenetic group II). The results obtained in this study showed induction of strong M2e-specific humoral response (serum IgG and A) in the immunized mice. Immunization with recombinant protein stimulated formation of M2e-specific and virus-specific CD4+ and CD8+T cells in lung which produced TNFα or IFNγ. Production of antigen-specific effector and central memory T cells was also detected in lungs of immunized mice. The formation of cross-protective immunity in immunized mice was demonstrated in a model of lethal influenza infection. The experimental animals were almost completely protected from the high dose of the pandemic virus A/H1N1pdm09, and highly pathogenic avian influenza A/H7N9 (90-100% survival). We also evaluated the changes of antigen-specific immune response in immunized mice after sublethal infection with A/H3N2 influenza virus. Mice of control and experimental groups were infected with MID100 of influenza virus A/Aichi/2/68 (H3N2). It was shown that the M2e-specific response (IgG, IgA) was significantly increased in immunized mice after sublethal infection with influenza virus A/H3N2, and we detected the changes in profile of M2e-specific IgG subclasses. Following sublethal infection in immunized mice, the proportion of M2e-specific IgG2a was increased 10-fold. The results showed that the recombinant protein Flg-HA2-2-4M2e is a promising candidate for development of universal vaccines, which induces a protective humoral and T-cell response to conserved viral epitopes and protects against influenza A viruses of both phylogenetic groups.


2017 ◽  
Vol 62 (3) ◽  
pp. 109-114
Author(s):  
E. A. Mukasheva ◽  
L. I. Nikolaeva ◽  
P. I. Makhnovsky ◽  
E. S. Kirillova ◽  
L. V. Kolobukhina ◽  
...  

Serologic studies occupy a significant place in influenza diagnosis. The article presents an analysis of the developed experimental version of ELISA test-systems for the detection of specific antibodies to the virus influenza A(H1N1)pdm09, and their dynamics at different stages of infection as compared with those of the traditional HAI method. The study included 20 paired samples of serum from patients hospitalized at different stages of the disease with etiology associated with the influenza virus A(H1N1)pdm09. Two groups were formed on the basis of HAI data, which showed the presence or absence of significant growth of specific antibodies to the influenza virus A(H1N1)pdm09. The control group consisted of 20 serum samples from individuals without influenza but with chronic hepatitis C. To examine the virus specific antibody two types of ELISA test systems were used. The first system was intended for the detection of IgM to the influenza virus A(H1N1)pdm09; the second was used for revealing specific IgG. The study showed the accuracy and specificity of detectable IgM and IgG to the virus influenza A(H1N1)pdm09. The dynamics of specific IgG titers in 15 of the 20 pairs of sera was reliable. The increase in titers was more pronounced than in the HAI. IgM against influenza virus could be detected up to 10 days, although reliable dynamics of these antibodies was not detected in paired samples. The test system was specific for the determination of both IgG and IgM antibodies to the influenza virus A(H1N1)pdm09 and significantly more sensitive than HAI. Using this ELISA test system, it is possible to monitor the dynamics of IgG to this virus even in the absence of diagnostic increases in antibody titers in HAI.


2014 ◽  
Vol 19 (4) ◽  
pp. 4-11
Author(s):  
V. V Tsvetkov ◽  
E. G Deeva ◽  
D. M Danilenko ◽  
T. V Sologub ◽  
E. P Tikhonova

Unlike influenza epidemics which affect the population almost yearly, pandemics occur much less frequently, but have more severe medical and social consequences. The investigation of the nature of the course of all modern epidemics and pandemics are acquiring the particular rationale. Pandemic influenza A (H1N1) 2009 was caused by the virus of the mixed (triple) origin. In Russia, the first three cases of disease have been identified in Moscow from 21 to 10 June 2009. In the Far East - 2-2,5 months later compared to the European part of Russia. However, the epidemic of influenza in Russia caused by influenza virus A (H1N1) pdm09, began and developed more rapidly just in the Far East. The highest morbidity rate (10,2-10,3 per 100 people) was registered in the cities of the Far Eastern and Siberian regions. The phylogenetic analysis allowed to reveal the origin of the triple reassortant virus A (H1N1)pdm09 out of H1N1, H1N2, H3N2 avian/porcine/human virus. The performed analysis of functional domains of proteins of the influenza virus A (H1N1) pdm09 showed that modern pandemic influenza viruses have several principal genetic defects, the totality of which permits to rank them to moderately pathogenic viruses. High risk of the severe course of influenza and occurrence of complications was noted in three groups ofpatients: pregnant women, especially in the 3 trimester ofpregnancy, children under 2 years of age and patients with concomitant chronic respiratory and cardiovascular systems, as well as patients with endocrine disorders and obesity.


Author(s):  
V. S. Vakin ◽  
I. V. Amosova ◽  
E. M. Vojcekhovskaya ◽  
T. A. Timoshicheva ◽  
A. A. Vasileva ◽  
...  

Currently, the assessment of the immunogenic properties of influenza viruses as a part of influenza vaccines, is carried out by using seroprotection, seroconversion as well as the rate of increases in post-vaccination antibodies. At the same time, significant differences in the immunogenicity of vaccines related to dynamic formation of high antibody titers responsible for long-term protection of the vaccinated, are neglected.Influenza viruses such as A (H1N1) pdm09 that caused 2009-2010 pandemic continue to circulate in the population, therefore, the assessment of the immunogenic activity of vaccine viruses prepared during the pandemic period is interesting in for the methodology to prepare pandemic vaccines to be used in various groups (adults, children, elderly people).Analyzing immunogenicity of influenza vaccines used during the 2009-10 swine influenza pandemic and the post-pandemic period up to the year 2014 was carried out by applying the graphical method for assessing immunogenicity (immunographs) measured as follows: for each group of vaccinated subjects (depending on the vaccine used), an increased rate in antibody level was calculated and the graphs of immunogenicity were plotted. An increased rate of serum antibodies magnitude from vaccinated subjects and the number of sera (in%) with a given fold increase rate in antibody level from 1 to the maximum magnitude were plotted on the x- and y-axis, respectively. The proposed method for assessing immunogenicity allows to plot immunogenicity graphs regardless of the serum antibodies level found in volunteers. The assessment described above revealed a several features for developing immune response to the pandemic virus A (H1N1)pdm09 such as the lack of immune response in a substantial number of adult volunteers (25-27%%) and young children (60-70%%) after monovaccine administration. The reason for such immune response can be both an insufficient dose of vaccine-containing viral antigen and suppressed immune response caused by the influenza A(H1N1)pdm09.A study on the immunogenic properties for seasonal influenza vaccines containing the influenza A (H1N1) pdm09 virus antigen in the years 2010 - 2014 revealed a variety in emerging humoral immunity ranging from a short-term, low-frequency increase in antibodies from vaccinated children to the formation of high antibody titers in elderly.Practically, immunographic analysis of influenza vaccines particularly those derived from the influenza A (H1N1)pdm09 virus, may result in proposing recommendations to increase an antigenic load at the beginning of a pandemic cycle and/or block the suppressive properties of vaccine-contained viruses in pediatric vaccines, because escalating virus dose in the vaccine may not always be achievable in this case.


2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.


2019 ◽  
Vol 65 (6) ◽  
pp. 520-525 ◽  
Author(s):  
A.V. Mikurova ◽  
V.S. Skvortsov

The overall model for prediction of IC₅₀ values for inhibitors of neuraminidase influenza virus A and B has been created. It combines data about IC₅₀ values of complexes of 40 variants of neuraminidases of influenza A (7 serotypes) and B and three known inhibitors (oseltamivir, zanamivir, peramivir). The model also uses only data of enthalpy contributions to the potential energy of inhibitor/protein and substrate (MUNANA)/protein complexes. The calculation procedures are ported to use software with support of GPU accelerators, that significant decrease the computation time. The corresponding correlation coefficient (R²) for pIC₅₀ prediction was within 0.45-0.58, the SEM values of around 0.7 (the range of used pIC₅₀ data set is from 4.55 to 10.22).


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3915 ◽  
Author(s):  
Raquel Almansa ◽  
Pamela Martínez-Orellana ◽  
Lucía Rico ◽  
Verónica Iglesias ◽  
Alicia Ortega ◽  
...  

Background The interaction between influenza virus and the host response to infection clearly plays an important role in determining the outcome of infection. While much is known on the participation of inflammation on the pathogenesis of severe A (H1N1) pandemic 09-influenza virus, its role in the course of non-fatal pneumonia has not been fully addressed. Methods A systems biology approach was used to define gene expression profiles, histology and viral dynamics in the lungs of healthy immune-competent mice with pneumonia caused by a human influenza A (H1N1) pdm09 virus, which successfully resolved the infection. Results Viral infection activated a marked pro-inflammatory response at the lung level paralleling the emergence of histological changes. Cellular immune response and cytokine signaling were the two signaling pathway categories more representative of our analysis. This transcriptome response was associated to viral clearance, and its resolution was accompanied by resolution of histopathology. Discussion These findings suggest a dual role of pulmonary inflammation in viral clearance and development of pneumonia during non-fatal infection caused by the 2009 pandemic influenza virus. Understanding the dynamics of the host’s transcriptomic and virological changes over the course of the infection caused by A (H1N1) pdm09 virus may help identifying the immune response profiles associated with an effective response against influenza virus.


2020 ◽  
Vol 8 (10) ◽  
pp. 1610 ◽  
Author(s):  
Mitsuru Sada ◽  
Takeshi Saraya ◽  
Haruyuki Ishii ◽  
Kaori Okayama ◽  
Yuriko Hayashi ◽  
...  

Favipiravir was initially developed as an antiviral drug against influenza and is currently used in clinical trials against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (COVID-19). This agent is presumably involved in RNA chain termination during influenza virus replication, although the molecular interactions underlying its potential impact on the coronaviruses including SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) remain unclear. We performed in silico studies to elucidate detailed molecular interactions between favipiravir and the SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza virus RNA-dependent RNA polymerases (RdRp). As a result, no interactions between favipiravir ribofuranosyl-5′-triphosphate (F-RTP), the active form of favipiravir, and the active sites of RdRps (PB1 proteins) from influenza A (H1N1)pdm09 virus were found, yet the agent bound to the tunnel of the replication genome of PB1 protein leading to the inhibition of replicated RNA passage. In contrast, F-RTP bound to the active sites of coronavirus RdRp in the presence of the agent and RdRp. Further, the agent bound to the replicated RNA terminus in the presence of agent, magnesium ions, nucleotide triphosphate, and RdRp proteins. These results suggest that favipiravir exhibits distinct mechanisms of action against influenza virus and various coronaviruses.


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