Progress in universal influenza vaccines targeting hemagglutinin and other conserved epitopes of influenza A virus / 中华微生物学和免疫学杂志

Influenza viruses are responsible for a large number of infections and deaths annually, posing a serious threat to public health. Vaccination is the most effective measure to prevent influenza virus infection. However, current seasonal influenza vaccines only protect against closely matched circulating strains. Even with extensive surveillance and annual reformulation, yearly updated vaccines are still a step behind the fast-evolving viruses, often resulting in poor matches or less effective vaccines. Due to the relatively complex evolution of influenza A viruses, it is a new idea and a new means to prevent influenza epidemics by using a series of innovative technologies to develop universal influenza vaccines that can provide extensive and long-lasting protection against influenza viruses. This review summarized the latest progress in the development of universal vaccines targeting HA in the past three years, including design methods for universal vaccines targeting HA, HA stem and other conserved epitopes, compared the advantages and disadvantages of different technologies, explored the impact of immunization programs and strategies, and discussed the potential challenges to be overcome, hoping to provide reference for the successful development of universal vaccines.

Eosinophilic Gastrointestinal Disorder Presenting as Intractable Vomiting and Ascites in a Young Girl / 대한소아소화기영양학회지

Eosinophilic gastrointestinal disorder (EGID) is a rare disease in children that affects the bowel wall, with eosinophilic infiltration in the absence of any other causes for eosinophilia. The etiology remains unknown, but allergies and immunological imbalance are suspected triggers. We encountered a case of serosal EGID presenting as intractable vomiting and ascites in a 9-year-old girl, after influenza virus infection. Peripheral eosinophilia was not present. The diagnosis was confirmed by biopsy of the bowel wall through laparotomy and endoscopy, and controlled by 2 courses of steroid therapy due to recurring symptoms. Influenza virus infection was assumed to play a role in the onset of EGID through a Th2 response that stimulated eosinophilic infiltration in the GI tract. We therefore report this case along with a literature review.

Efeitos do análogo triazólico da Ribavirina, PAR038, sobre a replicação in vitro do vírus influenza / Effects of a ribavirin triazolic analogue, PAR038, in the in vitro replication of influenza virus

Os vírus influenza representam uma das principais causas das infecções respiratórias agudas, e são de grande impacto para saúde pública devido a ocorrência de epidemias sazonais e pandemias. A variabilidade genética deste vírus e seu amplo espectro de hospedeiros dificulta o controle das infecções através da vacinação, o que torna os antivirais importantes na prevenção e tratamento. Até o presente momento, existem duas classes de antivirais disponíveis para o tratamento da infecção pelo vírus influenza, os bloqueadores de canal M2 (amandadina e rimantadina), que não são mais utilizados clinicamente pois as cepas circulantes são resistentes e os inibidores de neuraminidase (NAIs – oseltamivir e zanamivir), classe em uso clínico embora já tenham sido descritas cepas resistentes ao oseltamivir. Existe também a ribavirina, um antiviral de amplo espectro que inibe DNA/RNA polimerases virais mas é altamente citotóxico. Devido ao número limitado de drogas anti-influenza, vem sendo realizados estudos sobre a eficácia da ribavirina e sua combinação com NAIs para tratamento das infecções causadas pelo influenza. A RNA polimerase do vírus influenza vem sendo cada vez mais explorada como alvo para novas drogas, e, desta forma, o objetivo deste trabalho foi investigar o efeito antiviral do PAR038, um análogo triazólico da ribavirina como potencial inibidor da polimerase. O composto PAR038 se mostrou menos citotóxico para células MDCK e 400 vezes mais potente que a ribavirina, com CC50 > 1000 miM e IC50 = 0,07 miM. Nosso composto foi capaz de inibir a RNA polimerase do vírus influenza com EC50 igual a 1,6 +/- 0.15 miM, além de inibir a replicação viral em células A549 (IC50 = 21,2 miM) e apresentar propriedades imunomodulatórias, já que diminuiu os níveis de IL-8 e MCP-1 no sobrenadante das células A549 infectadas com o vírus influenza...

Influenza virus represents one of the main causes of acute respiratory infections, beinga major cause of mortality, morbidity and burden to public health system. The geneticvariability of influenza viruses and broad spectrum of these viruses` hosts impose difficultiesin control strategies through vaccination. Therefore, antiviral drugs have become critical in theprevention and treatment of the infections caused by influenza viruses. There are two classesof anti-influenza drugs, M2 channel blockers (amantadine and rimantadine), which are nolonger used since circulating strains are resistant to these antivirals, and neuraminidaseinhibitors (NAIs – oseltamivir and zanamivir), in clinical use. Despite that, oseltamivirresistantstrains have been described. An additional antiviral, ribavirin, is endowed with abroad spectrum activity against DNA/RNA polymerases, although high cytotoxic has beendescribed. Due to the limited number of anti-influenza drugs, studies have been carried out onthe effectiveness of ribavirin and its combination with NAIs for treating influenza infections.Thus, influenza RNA polymerase still is a valid target for development of novel antiviral.Based on that, we aimed here to investigate the antiviral effect of PAR038, a triazolicanalogue of ribavirin. PAR038 is 400-fold potent than ribavirin, with CC50 > 1000 µM andIC50 = 0,07 µM towards MDCKs cytotoxicity and influenza in vitro replication. Ourcompound inhibits influenza RNA polymerase with an EC50 of 1,6 ± 0,15 µM and alsoinhibits viral replication in an A549 cells (IC50 = 21,2 µM)...

Avian and human influenza A virus receptors in trachea and lung of animals.

Background: Influenza A viruses are capable of crossing the specific barrier between human beings and animals resulting in interspecies transmission. The important factor of potential infectivity of influenza A viruses is the suitability of the receptor binding site of the host and viruses. The affinities of avian and human influenza virus to bind with the receptors and the distributions of receptors in animals are different. Objective: This study aims to investigate the anatomical distribution of avian and human influenza virus receptors using the double staining lectin histochemistry method. Methods: Double staining of lectin histochemistry was performed to identify both SA α2,3 Gal and SA α2,6 Gal receptors in trachea and lung tissue of dogs, cats, tigers, ferret, pigs, ducks and chickens. Results: We have demonstrated that avian and human influenza virus receptors were abundantly present in trachea, bronchus and bronchiole, but in alveoli of dogs, cats and tigers showed SA α2,6 Gal only. Furthermore, endothelial cells in lung tissues showed presence of SA α2,3 Gal. Conclusion: The positive sites of both receptors in respiratory tract, especially in the trachea, suggest that all mammalian species studied can be infected with avian influenza virus. These findings suggested that dogs and cats in close contact with humans should be of greater concern as an intermediate host for avian influenza A in which there is the potential for viral adaptation and reassortment.