Microbiology Independent Research Journal (MIR Journal)
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Эпидемия гриппа в России в сезон 2014–2015 гг.
Get PDFThe goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in 2014–2015 season with the previous epidemic of 2013-2014. The data on weekly morbidity, hospitalization, deaths from influenza and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza. Analysis of this data showed, that the influenza epidemic in 2014-2015 began earlier (in December), compared with the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic 2014-2015 was higher, compared to the previous one. The epidemic was more prevalent by regions and cities and wider engagement of different age groups (except children up to 2 years) was observed. At the peak of the epidemic the morbidity level was higher, the average duration of the epidemic was longer and the number of patients among cities inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and ARI among patients older than 65 years were also higher (1.4 times) as well as frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times). Although the pandemic influenza virus A(H1N1)pdm09, was not the main causative agent of the epidemic 2015, it still was the main cause of deaths from influenza (45.5% of all cases). In spite of influenza A(H1N1)pdm09 virus sporadic prevalence, deaths from it were reported only on the European part of territory of Russia.Целью работы было сравнение показателей интенсивности эпидемии гриппа, вызванной штаммами вирусов гриппа А(H3N2) и В, в сезон 2014–2015 гг. с предшествующей эпидемией 2013–2014 гг. Особое внимание уделено летальным исходам от гриппа. Использована база данных НИИ гриппа по еженедельной заболеваемости, госпитализации, летальным исходам от гриппа и ОРЗ в различных возрастных группах населения 59-ти наблюдаемых городов, расположенных в семи Федеральных округах Российской Федерации. По сравнению с эпидемией 2014 г. эпидемия гриппа в 2014–2015 гг. началась раньше (в декабре) и распространялась, в основном, с запада на восток – из Европы по территории России в восточном направлении. Показатели интенсивности эпидемии 2015 г., в сравнении с предыдущей, были выше в отношении распространенности по округам, городам и вовлеченности возрастных групп населения (кроме детей до 2-х лет). Показатели заболеваемости на пике эпидемии, средней продолжительности эпидемии, уровней заболеваемости населения в городах (особенно среди детей 7–14 лет и взрослого населения) были выше, чем в предыдущем сезоне. Участились и случаи госпитализации с гриппом и OPВИ среди лиц старше 65 лет (в 1.4 раза), среди госпитализированных повысилась доля больных с диагнозом «грипп» (в 2.7 раза) и число летальных исходов от лабораторно подтвержденного гриппа (в 1.8 раза). Штамм пандемического вируса гриппа, A(H1N1)pdm09, хотя и не был основным возбудителем эпидемии 2015 г., попрежнему стал основной причиной летальных исходов от гриппа (в 45.5% всех случаев); причем случаи смерти, ассоциированные с этим штаммом, регистрировали только на европейской территории России при спорадическом уровне его распространения
Mutations in human genes that increase the risk for severe influenza infection
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.The 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
Использование микрокультурального иммуноферментного анализа для субтиповой идентификации циркулирующих вирусов гриппа А(Н1) и А(Н3)
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 the infected MDCK cells. The detection step of this method is an interaction of the subtype-specific monoclonal antibodies (mAbs) with the viral hemagglutinin (НА). The influenza A virus strains, isolated in 2014 epidemic season, were used to validate this method. It was shown that by using mAb # 1/ # 2 or # 4 at a concentration of 10-15 µg / ml the developed variant of cell-ELISA allows the detection of НА protein, synthesized in the cells infected with influenza A(H3N2) or A(H1N1)pdm09 virus, respectively. The developed method can be used for identification of HA subtype of modern influenza A viruses with low HA activity, which is not possible by the conventional hemagglutination inhibition test.Разработан чувствительный вариант микрокультурального ИФА (cell-ELISA) для субтиповой дифференциации современных вирусов гриппа А(Н1N1)pdm09 и А(Н3N2), циркулирующих в человеческой популяции. Метод основан на оценке репродукции вируса в инфицированной культуре клеток MDCK c использованием на стадии детекции cубтип-специфичных моноклональных антител (mAb), взаимодействующих с гемагглютинином (HA) вируса гриппа. При отработке метода использованы штаммы вирусов гриппа A, выделенные из клинических образцов в эпидемический сезон 2014 года. Показано, что при использовании mAb #1/#2 или #4 в концентрации 10–15 мкг/мл разработанный вариант cell-ELISA позволяет детектировать синтезируемый в зараженных клетках белок HA соответственно вирусов гриппа А(H3N2) или A(H1N1)pdm09. Разработанный метод может быть использован для идентификации современных штаммов вируса гриппа А в процессе их репродукции в клеточной культуре MDCK, что позволяет проводить субтипирование вирусов с низкой гемагглютинирующей активностью, когда невозможно использовать общепринятый метод – реакцию торможения гемагглютинации (РТГА)
The influenza epidemic in Russia during the 2014–2015 season
Get PDFThe goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in the 2014–2015 season with the previous epidemic of the 2013-2014 season. The data on weekly morbidity, hospitalization, deaths from influenza, and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza.Analysis of this data showed that the influenza epidemic in 2014-2015 began earlier (in December) compared to the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic of 2014-2015 was higher compared to the previous one. The epidemic was more prevalent by regions and cities and a wider engagement of different age groups (except children up to 2 years of age) was observed. At the peak of the epidemic, the morbidity level was higher, the average duration of the epidemic was longer, and the number of patients among cities’ inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and acute respiratory viral infections (ARVI) among patients older than 65 years were also higher (1.4 times) as well as the frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times).Although the influenza pandemic virus strain A(H1N1)pdm09 was not the main causative agent of the 2015 epidemic and was distributed sporadically it still remained the leading cause of deaths from influenza in the course of this epidemic (45.5% of all cases). The deaths associated with this strain were recorded only in the European part of Russian Federation.The goal of this study was to compare the data on the intensity of the influenza A(H3N2) and B epidemic (especially the death toll) in the 2014–2015 season with the previous epidemic of the 2013-2014 season. The data on weekly morbidity, hospitalization, deaths from influenza, and acute respiratory diseases in different age groups of inhabitants of 59 cities located in 7 Federal districts of the Russian Federation were collected using the database of the Research Institute of Influenza. Analysis of this data showed that the influenza epidemic in 2014-2015 began earlier (in December) compared to the epidemic of 2013-2014, and spread mainly from Europe through Russia to the East. The intensity of the epidemic of 2014-2015 was higher compared to the previous one. The epidemic was more prevalent by regions and cities and a wider engagement of different age groups (except children up to 2 years of age) was observed. At the peak of the epidemic, the morbidity level was higher, the average duration of the epidemic was longer, and the number of patients among cities’ inhabitants (especially among children 7-14 years of age and adults) was higher than in the previous season. The rates of hospitalization with influenza and acute respiratory viral infections (ARVI) among patients older than 65 years were also higher (1.4 times) as well as the frequency of hospitalization with a diagnosis of “influenza” (2.7 times) and the number of deaths from laboratory confirmed influenza (1.8 times). Although the influenza pandemic virus strain A(H1N1)pdm09 was not the main causative agent of the 2015 epidemic and was distributed sporadically it still remained the leading cause of deaths from influenza in the course of this epidemic (45.5% of all cases). The deaths associated with this strain were recorded only in the European part of Russian Federation
H5N1 influenza vaccine quality is affected by hemagglutinin conformational stability
Get PDFSince 1997, highly pathogenic H5N1 avian influenza viruses have circulated in wild and domestic birds and sporadically have infected humans. Conventional inactivated vaccines made from these viruses were shown to have decreased HA content and immunogenicity compared to seasonal preparations. We assumed that the high pH threshold (5.6-6.0) known for the HA conformational change (pH of fusion or activation) of avian highly pathogenic influenza viruses resulted in the low stability of native HA conformation and affected the vaccine quality. The 58Lys→Ile mutation introduced into the HA2 subunit of the HA of A/chicken/Kurgan/5/05 (H5N1) virus decreased the pH threshold of the HA activation. The mutant virus demonstrated increased HA stability toward acidic pH and elevated temperature, decreased binding efficiency to the monoclonal antibody IIF4 that recognizes the HA low pH form, and increased HA resistance to trypsin digestion. Virus with modified HA was less susceptible to freezing stress and showed an increased content of immunocompetent HA in inactivated vaccine preparation compared to the analogous virus with original HA. Therefore, we have shown a way to increase the quality of inactivated vaccines made from highly pathogenic avian influenza viruses.Since 1997, highly pathogenic H5N1 avian influenza viruses have circulated in wild and domestic birds and sporadically have infected humans. Conventional inactivated vaccines made from these viruses were shown to have decreased HA content and immunogenicity compared to seasonal preparations. We assumed that the high pH threshold (5.6-6.0) known for the HA conformational change (pH of fusion or activation) of avian highly pathogenic influenza viruses resulted in the low stability of native HA conformation and affected the vaccine quality. The 58Lys→Ile mutation introduced into the HA2 subunit of the HA of A/chicken/Kurgan/5/05 (H5N1) virus decreased the pH threshold of the HA activation. The mutant virus demonstrated increased HA stability toward acidic pH and elevated temperature, decreased binding efficiency to the monoclonal antibody IIF4 that recognizes the HA low pH form, and increased HA resistance to trypsin digestion. Virus with modified HA was less susceptible to freezing stress and showed an increased content of immunocompetent HA in inactivated vaccine preparation compared to the analogous virus with original HA. Therefore, we have shown a way to increase the quality of inactivated vaccines made from highly pathogenic avian influenza viruses
Влияние конформационной стабильности гемагглютинина вируса гриппа на качество инактивированных вакцин H5N1
Get PDFSince 1997, highly pathogenic H5N1 avian influenza viruses have circulated in wild and domestic birds and sporadically have infected humans. Conventional inactivated vaccines made from these viruses were shown to have decreased HA content and immunogenicity compared to seasonal preparations. We assumed that the high pH threshold (5.6-6.0) known for the HA conformational change (pH of fusion or activation) of avian highly pathogenic influenza viruses resulted in the low stability of native HA conformation and affected the vaccine quality. The 58Lys→Ile mutation introduced into the HA2 subunit of the HA of A/chicken/Kurgan/5/05 (H5N1) virus decreased the pH threshold of the HA activation. The mutant virus demonstrated increased HA stability toward acidic pH and elevated temperature, decreased binding efficiency to the monoclonal antibody IIF4 that recognizes the HA low pH form, and increased HA resistance to trypsin digestion. Virus with modified HA was less susceptible to freezing stress and showed an increased content of immunocompetent HA in inactivated vaccine preparation compared to the analogous virus with original HA. Therefore, we have shown a way to increase the quality of inactivated vaccines made from highly pathogenic avian influenza viruses.Начиная с 1997 года, в популяции диких и домашних птиц наблюдается постоянная циркуляция высокопатогенных вирусов гриппа подтипа H5N1. Периодически эти вирусы инфицируют людей, что создает угрозу возникновения новой пандемии. При производстве инактивированных вакцин из вирусов H5N1 замечено, что содержание главного компонента – антигена гемагглютинина (HA) – гораздо ниже, чем в аналогичных препаратах сезонных вирусов гриппа. Мы предположили, что урожайность НА определяется его стабильностью. Белки HA, входящие в состав вирионов высокопатогеннных вирусов гриппа птиц, отличаются от HA человеческих изолятов вируса гриппа высоким порогом рН-слияния, или рН-активации (5.6–6.0 vs 5.0–5.4), – значение pH, при котором НА изменяет конформацию, переходя в форму, необходимую для проникновения вируса в клетку. Нами получен мутантный вариант НА вируса A/chicken/Kurgan/5/05 (H5N1) с единственной заменой 58Lys→Ile, находящейся в HA2 субъединице белка. По сравнению с НА дикого типа у мутантного варианта порог рН-активации снижен, а стабильность увеличена как в кислой среде, так и при повышенной температуре. Кроме того, вирионы, содержащие мутантный НА, оказались более устойчивы к расщеплению трипсином и при их замораживании/размораживании нативная структура шипов HA сохранялась лучше, чем в родительском вирусе. Повышенная стабильность мутантного НА корреливала с увеличением его продукции как антигена в вакцинном препарате. Таким образом, высокое значение рН-активации НА высокопатогенных штаммов вируса гриппа H5N1 определяет низкую конформационную стабильность НА и, как следствие, низкую стабильность вирионов, что влияет на качество получаемых из них вакцинных препаратов