Microbiology Independent Research Journal (MIR Journal)
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Новая безопасная и эффективная живая модифицированная холодоадаптированная вирусная вакцина против гриппа лошадей, позволяющая дифференцировать инфицированных животных от вакцинированных
Get PDFAn analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of developed equine vaccine include: long lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus in 12 months after a double vaccination and the differentiation of infected animals from vaccinated animals.В настоящей работе дается анализ основных преимуществ и недостатков применяемых на практике инактивированных и живых вакцин против гриппа лошадей. Впервые обобщены наиболее значимые сведения, касающиеся разработки новой живой модифицированной холодоадаптированной вирусной вакцины против гриппа лошадей на основе штамма А/HK/ Otar/6:2/2010. Обсуждается ряд уникальных свойств разработанной вакцины, о которых ранее не сообщалось, в сравнении с аналогичными вакцинами против гриппа лошадей. К числу подобных свойств вакцины относятся: продолжительный (не менее 12 месяцев) протективный иммунитет после однократной вакцинации; стерильный иммунитет после двукратной вакцинации; перекрестная защита от гетерологичного вируса через 12 месяцев после двукратной вакцинации; дифференциация инфицированных животных от вакцинированных
Development of the A/H6N1 influenza vaccine candidate based on A/Leningrad/134/17/57 (H2N2) master donor virus and the genome composition analysis using high resolution melting (HRM)
Get PDFThe avian influenza viruses of H6N1subtype present a potential danger for humans. The cold-adapted (ca) reassortant influenza virus А/17/herring gull/Sarma/2006/887 (H6N1) was obtained in chicken embryos by the genetic reassortment based on the coldadapted A/Leningrad/134/17/57 (H2N2) master strain. The genome composition of the obtained reassortant was analyzed by means of real-time PCR with the high resolution melting (HRM) analysis using the intercalating fluorescent dye EvaGreen. Analysis of the gene segments showed that the reassortant А/17/herring gull/Sarma/2006/887 (H6N1) contains the internal proteins coding genes (PB2, PB1, PA, NP, M, and NS) of the master donor virus and the surface antigens coding genes of the A/herring gull/Sarma/51c/2006 (H6N1) avian influenza virus. The study of the phenotypic properties showed that the virus А/17/herring gull/Sarma/2006/887 (H6N1) is temperature sensitive (ts), ca in chicken embryos, and attenuated in mice when administered intranasally. This reassortant can be recommended as a live influenza vaccine candidate for humans.The avian influenza viruses of H6N1subtype present a potential danger for humans. The cold-adapted (ca) reassortant influenza virus А/17/herring gull/Sarma/2006/887 (H6N1) was obtained in chicken embryos by the genetic reassortment based on the coldadapted A/Leningrad/134/17/57 (H2N2) master strain. The genome composition of the obtained reassortant was analyzed by means of real-time PCR with the high resolution melting (HRM) analysis using the intercalating fluorescent dye EvaGreen. Analysis of the gene segments showed that the reassortant А/17/herring gull/Sarma/2006/887 (H6N1) contains the internal proteins coding genes (PB2, PB1, PA, NP, M, and NS) of the master donor virus and the surface antigens coding genes of the A/herring gull/Sarma/51c/2006 (H6N1) avian influenza virus. The study of the phenotypic properties showed that the virus А/17/herring gull/Sarma/2006/887 (H6N1) is temperature sensitive (ts), ca in chicken embryos, and attenuated in mice when administered intranasally. This reassortant can be recommended as a live influenza vaccine candidate for humans
Проблема создания универсальной противогриппозной вакцины
Get PDFPeriodically emerging new influenza strains along with the lack of population immunity to these new viruses can lead to a pandemic, making influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is one of the reasons for the existing influenza virus antigenic diversity in nature and the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, however, the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity developed after disease or immunization poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting wide cross-protective immunity, and is able to resist to influenza A and B viruses of all known subtypes. Basic approaches and challenges in creating such a vaccine are discussed in this review.Периодически появляющиеся новые пандемические штаммы вируса гриппа А, к которым отсутствует популяционный иммунитет, превращают грипп в особо опасную инфекцию. Сегментированная природа генома вируса гриппа способствует образованию реассортантов – вирусов, в состав которых входят геномные сегменты разных штаммов, принадлежащих одному роду. Именно механизм реассортации является основной причиной антигенного разнообразия вирусов гриппа в природе и появления штаммов, вызывающих пандемии в человеческой популяции. Лучшим средством предотвращения распространения гриппозной инфекции считается вакцинация. Однако эффективность известных на сегодняшний день вакцин недостаточна, особенно при иммунизации пожилых людей и маленьких детей. Специфический иммунитет, вырабатываемый после перенесенного заболевания или вакцинации одним подтипом вируса гриппа, слабо защищает от инфекции вирусом другого подтипа. В связи с этим не потерял актуальности вопрос разработки эффективной универсальной гриппозной вакцины, которая будет индуцировать широкий кросс-протективный длительный иммунитет как к вирусам гриппа А различных подтипов, так и к вирусам гриппа В. Основные подходы к созданию такой вакцины и проблемы их реализации рассматриваются в данном обзоре
The challenges of creating a universal influenza vaccine
Get PDFThe lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review.The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review
A new safe and effective cold-adapted modified live equine influenza virus vaccine that enables the differentiation of infected from vaccinated animals
Get PDFAn analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses (EIVs) is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted (ca) equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of the developed equine vaccine include: long-lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus at 12 months after double vaccination and the differentiation of infected from vaccinated animals.An analysis of the main advantages and shortcomings of the existing inactivated and live vaccines against the equine influenza viruses (EIVs) is given in this paper. For the first time, the most important information, concerning the development of a new live modified cold-adapted (ca) equine influenza virus vaccine based on the A/HK/Otar/6:2/2010 strain is summarized. We discuss a number of unique features of the developed vaccine that have not previously been reported, and compare the new vaccine with the existing equine influenza vaccines. The properties of the developed equine vaccine include: long-lasting (12 months or more) protective immunity after a single immunization; sterile immunity after double vaccination; cross-protection against the heterologous virus at 12 months after double vaccination and the differentiation of infected from vaccinated animals
Мутации в генах человека, повышающие риск тяжелого течения гриппозной инфекции
Get PDFThe system of genetic control of innate immune responses to influenza infection and gene function allows for the development of systemic treatment of influenza with a focus on the phenotype of mutations based on individual genetic susceptibility to severe disease and/or the development of complications.Система генетического контроля реакции врожденного иммунитета на гриппозную инфекцию и функции генов позволяет вести разработку системного лечения гриппа с ориентацией на фенотипические проявления мутаций с учетом наследственной предрасположенности индивида к тяжелому течению заболевания и/или развитию осложнений
Changes in the antigenic and genetic structure of influenza viruses: analysis of surveillance data of influenza A and B in Russia in 2006-2013
Get PDFThe goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses.The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals.Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013.The goal of this research project was to study the natural variability of human influenza A and B viruses based on the analysis of the population structure of influenza viruses, circulating in Russia in 2006-2013, in order to determine the direction of their genetic and antigenic drift by comparison to the WHO reference strains. Our results proved that during that period significant changes occurred in the genetic structure of influenza viruses, their phylogenetic affiliation, as well as their sensitivity to antiviral drugs. According to the surveillance data, the percentage of influenza A(H1N1) viruses among patients with influenza-like illness or acute respiratory infection gradually decreased from 42% of the total number of influenza viruses in 2006-2007 to 19% in 2008- 2009. Influenza A(H1N1) viruses are characterized by «silent» variability that manifests in the gradual accumulation of amino acid substitutions in the minor undetectable group of viruses. The share of influenza A(H3N2) viruses varied from 10% in the 1st post pandemic year to approx. 60% in 2008-2009 and 2011- 2012 epidemic seasons. All of the influenza A strains isolated during the last years of the period, covered in this study, were found to be susceptible to neuraminidase inhibitors and resistant to adamantane antivirals. Influenza B viruses of both Yamagata and Victoria lineages circulated in Russia in the period from 2006 to 2013. The vast majority of these influenza B viruses belonged to the Victoria lineage. Phylogenetic and antigenic analyses of influenza B viruses have demonstrated a gradual drift of Russian isolates from the reference strains. No changes leading to resistance to oseltamivir or zanamivir were found in influenza B strains isolated until 2013
Two years of experience in hospital surveillance for the severe influenza like illnesses in St. Petersburg: etiology, clinical characterization of diseases, antigenic and genetic properties of isolated influenza viruses
Get PDFIn this paper, we analyze the etiology of the diseases occurring during two consecutive influenza epidemic seasons in St. Petersburg, Russian Federation. The analysis is based on the results of the PCR diagnostics of the clinical samples collected from patients hospitalized in three St. Petersburg hospitals with influenza like illnesses (ILI). It was shown that the influenza virus A(H1N1)pdm09 was the dominant causative agent during the 2012-2013 epidemic season while, in the 2013-2014 season, A(H3N2) virus was predominant among adults and children. The influenza B virus activity was high in the 2012-2013 season and low in the 2013-2014 season. During both seasons, the main causative agent for the hospitalization of young children was respiratory syncytial virus (RSV), followed by rhinovirus and influenza virus. The rate of involvement of parainfluenza, adenovirus, metapneumovirus and coronavirus was low and was negligible for bocavirus. Children 0-2 and 3-6 years old formed the group of patients that was affected by acute respiratory infection agents the most. Children younger than 3 months old were the major group of the intensive care unit (ICUs) patients and only 27.5% of them were adults. RSV and rhinovirus were the leading cause of ILI among the children admitted to ICU. Among the adult patients admitted to the ICU, only influenza A(H1N1)pdm09, A(H3N2) and B viruses were detected during both influenza seasons.According to the results of the antigenic and genetic analysis, most influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in St. Petersburg matched the vaccine strains recommended by the WHO for vaccine composition in the 2012-2013 and 2013-2014 seasons.In this paper, we analyze the etiology of the diseases occurring during two consecutive influenza epidemic seasons in St. Petersburg, Russian Federation. The analysis is based on the results of the PCR diagnostics of the clinical samples collected from patients hospitalized in three St. Petersburg hospitals with influenza like illnesses (ILI). It was shown that the influenza virus A(H1N1)pdm09 was the dominant causative agent during the 2012-2013 epidemic season while, in the 2013-2014 season, A(H3N2) virus was predominant among adults and children. The influenza B virus activity was high in the 2012-2013 season and low in the 2013-2014 season. During both seasons, the main causative agent for the hospitalization of young children was respiratory syncytial virus (RSV), followed by rhinovirus and influenza virus. The rate of involvement of parainfluenza, adenovirus, metapneumovirus and coronavirus was low and was negligible for bocavirus. Children 0-2 and 3-6 years old formed the group of patients that was affected by acute respiratory infection agents the most. Children younger than 3 months old were the major group of the intensive care unit (ICUs) patients and only 27.5% of them were adults. RSV and rhinovirus were the leading cause of ILI among the children admitted to ICU. Among the adult patients admitted to the ICU, only influenza A(H1N1)pdm09, A(H3N2) and B viruses were detected during both influenza seasons. According to the results of the antigenic and genetic analysis, most influenza A(H1N1)pdm09 and A(H3N2) viruses circulating in St. Petersburg matched the vaccine strains recommended by the WHO for vaccine composition in the 2012-2013 and 2013-2014 seasons
Development of the cell-ELISA test for the subtype identification of circulating influenza A(H1) and A(H3) viruses
Get PDFThe sensitive version of cell-ELISA was developed for the subtype-specific differentiation of current influenza A(H1N1)pdm09 and A(H3N2) viruses that are circulating in the human population. This method is based on the estimation of virus reproduction in infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА) molecule. The influenza A virus strains, isolated in the 2014 epidemic season, were used to validate this method.It was shown that when using mAbs # 1/ # 2 or # 4 at a concentration of 10-15 µg/ml, the developed variant of cell-ELISA was able to detect НА protein synthesized in the infected cells of influenza A(H3N2) and A(H1N1)pdm09 viruses, respectively.The developed method can be used for the identification of modern influenza A viruses with low hemagglutination activity, which is not possible by the conventional hemagglutination inhibition test.The sensitive version of cell-ELISA was developed for the subtype-specific differentiation of current influenza A(H1N1)pdm09 and A(H3N2) viruses that are circulating in the human population. This method is based on the estimation of virus reproduction in infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА) molecule. The influenza A virus strains, isolated in the 2014 epidemic season, were used to validate this method. It was shown that when using mAbs # 1/ # 2 or # 4 at a concentration of 10-15 µg/ml, the developed variant of cell-ELISA was able to detect НА protein synthesized in the infected cells of influenza A(H3N2) and A(H1N1)pdm09 viruses, respectively. The developed method can be used for the identification of modern influenza A viruses with low hemagglutination activity, which is not possible by the conventional hemagglutination inhibition test