Comparison of Influenza Outbreaks in the Republic of Kazakhstan and Russia Induced by 2009 Yearly New Variant of А(H1N1) Influenza Virus

The aim of the work is the comparison of the epidemiology of influenza and acute respiratory virus infections (ARVI) in the Republic of Kazakhstan with the corresponding influenza epidemic in Russia induced by influenza pandemic virus A/California/07/2009 in 2009.Data on influenza and ARVI from the Republic of Kazakhstan and Federal Center of influenza was collected and investigated over the course of several weeks from hospitalized patients with the same diagnosis among all population and in age groups on ...     

Preventive measure of massive spreading of influenza and acute respiratory viral infections

Influenza and acute respiratory viral infections (ARVI) continue to be one of the most actual medical and social-economic problem. But problem of high incidence of ARVI often regarded as problem of influenza only. Information about methods of prognosis of massive spreading of ARVI complex and universal system of their prophylaxis including influenza is presented in the article.     

Comparison of influenza outbreaks in the Republic of Kazakhstan and Russia induced by 2009 yearly new variant of A(H1N1) influenza virus

The aim of the work is the comparison of the epidemiology of influenza and acute respiratory virus infections(ARVI)in the Republic of Kazakhstan with the corresponding influenza epidemic in Russia induced by influenza pandemic virus A/California/07/2009 in 2009. Data on influenza and ARVI from the Republic of Kazakhstan and Federal Center of influenza was collected and investigated over the course of several weeks from hospitalized patients with the same diagnosis among all population and in age groups on 16 territories of Kazakhstan and in 49 major cities of Russia. The epidemic in Kazakhstan resembled the Russian epidemic in terms of its abnormally early beginning,expression of monoaetiology,the spread of the epidemic into all territories and start of the epidemics among adult population. High percentage of hospitalized people and lethal outcome were registered in this epidemic. Similarity of epidemic process character in corresponding border-line territories of both countries was found out.     

Etiological structure of acute respiratory viral infections in children hospitalized in 1981-1999

The role of influenza and parainfluenza viruses, respiratory syncytial viruses and adenoviruses in the etiological structure of morbidity in acute respiratory virus infections (ARVI) in children hospitalized during the 19 year period is analyzed. As the result of examination of 56,287 patients by direct immunofluorescent test, respiratory viruses were detected in 21% of cases. The seasonal character, periodicity and level of ARVI morbidity were established. According to medical records, in the 1990s ARVI took a more severe course in children than that observed in the 1980s. In addition, the data on morbidity among children regarding rotavirus infection and ARVI were found to be similar.     

Incidence of avian flu worldwide and in the Russian Federation. Improvement of surveillance and control of influenza during preparation for potential pandemic

Problem of influenza and acute respiratory virus infections (ARVI) remains one of the most urgent medical and socio-economic issues in despite of certain achievements in vaccine and chemoprophylaxis. In Russia influenza and ARVI account for up to 90% of the total annual incidence of infectious disease (up to 30 million of sick people; 45-60% of them are children). Economic damage, caused by influenza and ARVI, makes around 86% of total economic damage, caused by infectious diseases. WHO predicts that in the years coming a new antigenic influenza virus will appear, which can lead to development of large pandemia with 4-5 times increase in disease incidence and 5-10 times increase in death rate. During 2005 some changes in animal influenza epidemiology were registered. New cases of people infections are detected, the virus has spread to some new countries. Avian influenza is a high contagious virus infection that can affect all bird species. For birds influenza is enteral infection, it severely affects parenchymatous organs, especially spleen, and lungs. By now it is known that carriers of avian influenza virus H5N1 can be all known species of wild waterfowl and near-water birds. Poultry is highly susceptible to many stocks of influenza virus H5N1, death rate reaches 100%. At that hens, especially chickens, are most susceptible. From January 2004 to 24th November 2005 in the world there were detected 131 cases of influenza, caused by virus A/H5N1/, 68 of them (51%) ended in lethal outcome (Vietnam--92 cases, Thailand--21 cases, Cambodia--4, Indonesia--11, China--3). Most of the described cases of avian influenza resulted from direct contact with infected birds (handling bird internal organs is especially dangerous). In frozen meat of infected birds the virus can remain for about one year. Heating kills virus (no cases of infection caused by use for food of poultry products were detected). In order to prevent wide ranging spread of infection over Russia it is necessary to organize medical monitoring of sea ships, aircraft and train crews, arriving from the countries where influenza H5N1 cases were detected, in case of need to arrange raids to outlets and markets to detect poultry and poultry products brought from these countries. In Russia it is necessary to prepare a reserve of vaccine strains of viruses--potential causative agent of pandemic, including H5N1 and H7N7, that can start to vaccine reproduction immediately in case of pandemic.     

Epidemiological and economic effectiveness of immunization of adult and children against influenza and acute respiratory viral infections with the vaccine Grippol

Materials on the characterization of the vaccine Grippol, indications for its use and the results of mass use are presented. Analysis of the morbidity level in influenza and acute respiratory viral infections (ARVI) among the vaccinated persons are indicative of considerably decreased level. The coefficient of the epidemiological effectiveness of Grippol in the immunization of children has proved to be 75-95%. The conclusion has been made that the vaccine Grippol is sufficiently effective and safe for use by Russian public health service.     

Prevalence and structure of acute respiratory virus infections

Information on epidemiology of acute respiratory virus infections (ARVI) is reviewed and analyzed. In addition to influenza viruses, the role of respiratory syncytial viruses (RSV), rhino- and adenoviruses, as well as other viruses, in the development of respiratory diseases, especially in newborns, young children and elderly persons, is emphasized. A high proportion of RSV in the etiology the severe forms of ARVI and in the development of intrauterine infection is pointed out. The conclusion has been made that the identification of the causative agents of ARVI with the use of modern methods makes it possible to determine the real role of each of the pathogens in the formation of the severe forms of diseases, as well as the expediency of vaccinal prophylaxis.     

Potent neutralization of influenza A virus by a single-domain antibody blocking M2 ion channel protein

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses.     

Induction of protective immunity against malaria by priming-boosting immunization with recombinant cold-adapted influenza and modified vaccinia Ankara viruses expressing a CD8+-T-cell epitope derived from the circumsporozoite protein of Plasmodium yoelii

We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8(+)-T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.     

Evaluation of amyxin effect in prophylaxis of acute respiratory viral infections

The results of the evaluation of the oral inductor of endogenic interferon (amyxin), manufactured in Russia are presented. The use of amyxin was found to produce a drop in morbidity in acute respiratory virus infections (ARVI) among medical workers 3.4 times, i.e. the preparation exhibited a pronounced prophylactic effect with respect to ARVI. The use of the preparation was accompanied by a decrease in the number of manifest forms of ARVI. Persons given the preparation often had ARVI in a mild or asymptomatic form.     

Protection of inactivated influenza virus vaccine against lethal influenza virus infection in diabetic mice

Influenza virus infection frequently causes complications and some excess mortality in the patients with diabetes. Vaccination is an effective measure to prevent influenza virus infection. In this paper, antibody response and protection against influenza virus infection induced by vaccination were studied in mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized once or twice with inactivated influenza virus vaccine at various dosages. Four weeks after the first immunization or 1 week after the second immunization, the mice were challenged with influenza virus at a lethal dose. The result showed that the antibody responses in diabetic mice were inhibited. Immunization once with high dose or twice with low dose of vaccine provided full protection against lethal influenza virus challenge in diabetic mice, however, in healthy mice, immunization only once with low dose provided a full protection.     

Memory T Cells Generated by Prior Exposure to Influenza Cross React with the Novel H7N9 Influenza Virus and Confer Protective Heterosubtypic Immunity

Influenza virus is a source of significant health and economic burden from yearly epidemics and sporadic pandemics. Given the potential for the emerging H7N9 influenza virus to cause severe respiratory infections and the lack of exposure to H7 and N9 influenza viruses in the human population, we aimed to quantify the H7N9 cross-reactive memory T cell reservoir in humans and mice previously exposed to common circulating influenza viruses. We identified significant cross-reactive T cell populations in humans and mice; we also found that cross-reactive memory T cells afforded heterosubtypic protection by reducing morbidity and mortality upon lethal H7N9 challenge. In context with our observation that PR8-primed mice have limited humoral cross-reactivity with H7N9, our data suggest protection from H7N9 challenge is indeed mediated by cross-reactive T cell populations established upon previous priming with another influenza virus. Thus, pre-existing cross-reactive memory T cells may limit disease severity in the event of an H7N9 influenza virus pandemic.     

Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge

There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.     

Heterosubtypic antibody response elicited with seasonal influenza vaccine correlates partial protection against highly pathogenic H5N1 virus

Background

The spread of highly pathogenic avian influenza (HPAI) H5N1 virus in human remains a global health concern. Heterosubtypic antibody response between seasonal influenza vaccine and potential pandemic influenza virus has important implications for public health. Previous studies by Corti et al. and by Gioia et al. demonstrate that heterosubtypic neutralizing antibodies against the highly pathogenic H5N1 virus can be elicited with a seasonal influenza vaccine in humans. However, whether such response offers immune protection against highly pathogenic H5N1 virus remained to be determined.

Methodology/Principal Findings

In this study, using a sensitive influenza HA (hemagglutinin) and NA (neuraminidase) pseudotype-based neutralization (PN) assay we first confirmed that low levels of heterosubtypic neutralizing antibody response against H5N1 virus were indeed elicited with seasonal influenza vaccine in humans. We then immunized mice with the seasonal influenza vaccine and challenged them with lethal doses of highly pathogenic H5N1 virus. As controls, we immunized mice with homosubtypic H5N1 virus like particles (VLP) or PBS and challenged them with the same H5N1 virus. Here we show that low levels of heterosubtypic neutralizing antibody response were elicited with seasonal influenza vaccine in mice, which were significantly higher than those in PBS control. Among them 2 out of 27 whose immune sera exhibited similar levels of neutralizing antibody response as VLP controls actually survived from highly pathogenic H5N1 virus challenge.

Conclusions/Significance

Therefore, we conclude that low levels of heterosubtypic neutralizing antibody response are indeed elicited with seasonal influenza vaccine in humans and mice and at certain levels such response offers immune protection against severity of H5N1 virus infection.     

Influenza virus-like particles containing M2 induce broadly cross protective immunity

Background

Current influenza vaccines based on the hemagglutinin protein are strain specific and do not provide good protection against drifted viruses or emergence of new pandemic strains. An influenza vaccine that can confer cross-protection against antigenically different influenza A strains is highly desirable for improving public health.

Methodology/Principal Findings

To develop a cross protective vaccine, we generated influenza virus-like particles containing the highly conserved M2 protein in a membrane-anchored form (M2 VLPs), and investigated their immunogenicity and breadth of cross protection. Immunization of mice with M2 VLPs induced anti-M2 antibodies binding to virions of various strains, M2 specific T cell responses, and conferred long-lasting cross protection against heterologous and heterosubtypic influenza viruses. M2 immune sera were found to play an important role in providing cross protection against heterosubtypic virus and an antigenically distinct 2009 pandemic H1N1 virus, and depletion of dendritic and macrophage cells abolished this cross protection, providing new insight into cross-protective immune mechanisms.

Conclusions/Significance

These results suggest that presenting M2 on VLPs in a membrane-anchored form is a promising approach for developing broadly cross protective influenza vaccines.     

A universal influenza A vaccine based on the extracellular domain of the M2 protein.

The antigenic variation of influenza virus represents a major health problem. However, the extracellular domain of the minor, virus-coded M2 protein is nearly invariant in all influenza A strains. We genetically fused this M2 domain to the hepatitis B virus core (HBc) protein to create fusion gene coding for M2HBc; this gene was efficiently expressed in Escherichia coli. Intraperitoneal or intranasal administration of purified M2HBc particles to mice provided 90-100% protection against a lethal virus challenge. The protection was mediated by antibodies, as it was transferable by serum. The enhanced immunogenicity of the M2 extracellular domain exposed on HBc particles allows broad-spectrum, long-lasting protection against influenza A infections.     

Pretreatment of outer membrane vesicle and subsequent infection with influenza virus induces a long-lasting adaptive immune response against broad subtypes of influenza virus

Influenza is an acute respiratory disease and a global health problem. Although influenza vaccines are commercially available, frequent antigenic changes in hemagglutinin might render them less effective or unavailable. We previously reported that modified outer membrane vesicle (fmOMV) provided immediate and robust protective immunity against various subtypes of influenza virus. However, the effect was transient because it was innate immunity-dependent. In this study, we investigated the effects of consecutive administration of fmOMV and influenza virus on the adaptive immune response and long-term protective immunity against influenza virus. When the mice were pretreated with fmOMV and subsequently infected with influenza virus, strong influenza-specific antibody and T cell responses were induced in both systemic and lung mucosal compartments without pathogenic symptoms. Upon the secondary viral challenge at week 4, the mice given fmOMV and influenza virus exhibited almost complete protection against homologous and heterologous viral challenge. More importantly, this strong protective immunity lasted up to 18 weeks after the first infection. These results show that pretreatment with fmOMV and subsequent infection with influenza virus efficiently induces broad and long-lasting protective immunity against various virus subtypes, suggesting a novel antiviral strategy against newly-emerging viral diseases without suitable vaccines or therapeutics.     

宠物犬和猫流感病毒感染

近十年来犬和猫流感病毒感染报道迅速增多,不仅威胁到犬和猫的健康,也对公共卫生造成了影响。自2004年首次发生H3N8亚型流感病毒感染赛犬事件以来,犬流感一直在美国的赛犬和宠物犬中流行。在韩国和我国南方的犬群中出现了因H3N2亚型禽流感感染引起的肺炎病例。亚洲和欧洲均报道了猫H5N1亚型高致病性禽流感致死性感染病例,还通过实验研究发现H5N1亚型流感病毒可在猫与猫之间水平传播。这些现象预示着流感病毒进一步获得了感染哺乳动物的能力,其公共卫生意义需引起关注。为此,本文对犬和猫流感病毒感染的流行病学、临床症状、发病机制、诊断和防控措施进行了综述。     

Pre-existing heterosubtypic immunity provides a barrier to airborne transmission of influenza viruses

Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne infection is still unknown. Using the ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We demonstrate that a 48 hour exposure is sufficient for efficient transmission of H1N1 and H3N2 viruses. To test pre-existing immunity, a gap of 8–12 weeks between primary and secondary infections was imposed to reduce innate responses and ensure robust infection of donor animals with heterosubtypic viruses. We found that pre-existing H3N2 immunity did not significantly block transmission of the 2009 H1N1pandemic (H1N1pdm09) virus to immune animals. Surprisingly, airborne transmission of seasonal H3N2 influenza strains was abrogated in recipient animals with H1N1pdm09 pre-existing immunity. This protection from natural infection with H3N2 virus was independent of neutralizing antibodies. Pre-existing immunity with influenza B virus did not block H3N2 virus transmission, indicating that the protection was likely driven by the adaptive immune response. We demonstrate that pre-existing immunity can impact susceptibility to heterologous influenza virus strains, and implicate a novel correlate of protection that can limit the spread of respiratory pathogens through the air.     

流感病毒交叉反应性记忆T细胞的研究进展

流感病毒是长期威胁人类健康最主要的病毒之一.灭活流感疫苗主要产生针对病毒血凝素的菌株特异性抗体,当新出现的流感病毒株与疫苗株不匹配时,疫苗的有效性将会大大降低.由于季节性流感病毒的抗原漂移和突变的持续出现,人们迫切地需要找到更广泛的保护方式.在以往的研究中,人们逐渐意识到细胞免疫的重要性,尤其是预先存在的记忆T细胞能靶...