Prevalence Of Influenza Viruses Research Articles

Intranasal administration of immunogenic poly-epitope from influenza H1N1 and H3N2 viruses adjuvanted with chitin and chitosan microparticles in BALB/c mice.

Objective(s):Prevalence of influenza virus, creates the need to achieve an efficient vaccine against it. We examined whether the predicted antigenic epitopes of HA, NP, and M2 proteins of the influenza H1N1 and H3N2 viruses accompanied by chitin and chitosan biopolymers might be relevant to the induction of effective proper mucosal responses. Materials and Methods:The construct was prepared using B and T cell predicted epitopes of HA, NP, and M2 proteins from the influenza H1N1 and H3N2 viruses by considering haplotype “d” as a dominant allele in the BALB/c mice. Intranasal immunization with purified LPS free recombinant protein together with chitin and chitosan microparticles as adjuvants was administered at an interval of 2 weeks in thirty-five BALB/c female mice which were divided into seven groups. Ten days after the last immunization, humoral and cellular immune responses were examined. Results:Elevated systemic IgG2a, IgA, and mucosal IgA revealed a humoral response to the construct. An increase in the number of IFN-γ-producing cells in re-stimulation of splenocytes in the culture medium by poly-tope as well as rise in the concentrations of IL-6, IL-17, and TNF-α along with the regulatory response of IL-10, presented the capacity of the designed protein to provoke significant immune responses. The neutralization test ultimately confirmed the high efficacy of the protein in inhibiting the virus. Conclusion:The results support the fact that immunogenic poly-tope protein in the presence of chitin and chitosan microparticles as mucosal adjuvants is able to induce humoral and cell-mediated responses in BALB/c mice.

Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection.

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

Aryl Sulfonamide Inhibits Entry and Replication of Diverse Influenza Viruses via the Hemagglutinin Protein.

Influenza viruses cause approximately half a million deaths every year worldwide. Vaccines are available but partially effective, and the number of antiviral medications is limited. Thus, it is crucial to develop therapeutic strategies to counteract this major pathogen. Influenza viruses enter the host cell via their hemagglutinin (HA) proteins. The HA subtypes of influenza A virus are phylogenetically classified into groups 1 and 2. Here, we identified an inhibitor of the HA protein, a tertiary aryl sulfonamide, that prevents influenza virus entry and replication. This compound shows potent antiviral activity against diverse H1N1, H5N1, and H3N2 influenza viruses encoding HA proteins from both groups 1 and 2. Synthesis of derivatives of this aryl sulfonamide identified moieties important for antiviral activity. This compound may be considered as a lead for drug development with the intent to be used alone or in combination with other influenza A virus antivirals to enhance pan-subtype efficacy.

Advances in Development and Application of Influenza Vaccines.

Influenza A virus is one of the most important zoonotic pathogens that can cause severe symptoms and has the potential to cause high number of deaths and great economic loss. Vaccination is still the best option to prevent influenza virus infection. Different types of influenza vaccines, including live attenuated virus vaccines, inactivated whole virus vaccines, virosome vaccines, split-virion vaccines and subunit vaccines have been developed. However, they have several limitations, such as the relatively high manufacturing cost and long production time, moderate efficacy of some of the vaccines in certain populations, and lack of cross-reactivity. These are some of the problems that need to be solved. Here, we summarized recent advances in the development and application of different types of influenza vaccines, including the recent development of viral vectored influenza vaccines. We also described the construction of other vaccines that are based on recombinant influenza viruses as viral vectors. Information provided in this review article might lead to the development of safe and highly effective novel influenza vaccines.

Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis.

Influenza is one of the most serious respiratory viral infections worldwide. Although several studies have reported that green tea catechins (GTCs) might prevent influenza virus infection, this remains controversial. We performed a systematic review and meta-analysis of eight studies with 5048 participants that examined the effect of GTC administration on influenza prevention. In a random-effects meta-analysis of five RCTs, 884 participants treated with GTCs showed statistically significant effects on the prevention of influenza infection compared to the control group (risk ratio (RR) 0.67, 95% CIs 0.51–0.89, p = 0.005) without evidence of heterogeneity (I2 = 0%, p = 0.629). Similarly, in three cohort studies with 2223 participants treated with GTCs, there were also statistically significant effects (RR 0.52, 95% CIs 0.35–0.77, p = 0.001) with very low evidence of heterogeneity (I2 = 3%, p = 0.358). Additionally, the overall effect in the subgroup analysis of gargling and orally ingested items (taking capsules and drinking) showed a pooled RR of 0.62 (95% CIs 0.49–0.77, p = 0.003) without heterogeneity (I2 = 0%, p = 0.554). There were no obvious publication biases (Egger’s test (p = 0.138) and Begg’s test (p = 0.103)). Our analysis suggests that green tea consumption is effective in the prophylaxis of influenza infections. To confirm the findings before implementation, longitudinal clinical trials with specific doses of green tea consumption are warranted.

Peculiarities of the inverted repeats in the complete chloroplast genome of Strobilanthes bantonensis Lindau

Strobilanthes bantonensis Lindau belongs to the family Acanthaceae. It is an antiviral herb that can be used to prevent Influenza virus infections in the border areas between China and Vietnam. Local people call it ‘Purple Ban-lan-gen’ because its root is very similar to that of Strobilanthes cusia (Nees) Kuntze, which is called ‘Southern Ban-lan-gen’ and is listed in Chinese Pharmacopeia. The two species have been used interchangeably locally. However, their pharmacological equivalence has caused concern for years. We have sequenced the chloroplast genome of S. cusia previously. In this study, we sequenced the complete chloroplast genome sequence of S. bantonensis to preform in-depth comparative genetic analysis of the two Strobilanthes species. The chloroplast genome of S. bantonensis is a circular DNA molecule with a total length of 144,591 bp and encodes 84 protein-coding, 8 ribosomes, and 37 transfer RNA genes. The chloroplast genome has a conservative quadripartite structure, including a large single-copy (LSC) region, a small single-copy (SSC) region, and a pair of inverted repeat (IR) regions, with lengths of 92,068 bp, 17,767 bp, and 17,378 bp, respectively. Phylogenetic analysis confirmed that S. bantonensis is closely related to the S. cusia. Compared with other species from Acanthaceae, S. bantonensis has a significantly shortened IR region, suggesting the occurrence of IR contraction events. This study will help future taxonomic, evolutionary, phylogenetic, and bioprospecting studies of the sizeable Strobilanthes genus, which contains over 400 species.

Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

While vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

Influenza Chimeric Protein (3M2e-3HA2-NP) Adjuvanted with PGA/Alum Confers Cross-Protection against Heterologous Influenza A Viruses.

Vaccination is the most effective way to prevent influenza virus infections. However, conventional vaccines based on hemagglutinin (HA) have to be annually updated because the HA of influenza viruses constantly mutates. In this study, we produced a 3M2e-3HA2-NP chimeric protein as a vaccine antigen candidate using an Escherichia coli expression system. The vaccination of chimeric protein (15 μg) conferred complete protection against A/Puerto Rico/8/1934 (H1N1; PR8) in mice. It strongly induced influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity. To spare the dose and enhance the cross-reactivity of the chimeric, we used a complex of poly-γ-glutamic acid and alum (PGA/alum) as an adjuvant. PGA/alum-adjuvanted, low-dose chimeric protein (1 or 5 μg) exhibited higher cross-protective effects against influenza A viruses (PR8, CA04, and H3N2) compared with those of chimeric alone or alum-adjuvanted proteins in vaccinated mice. Moreover, the depletion of CD4+ T, CD8+ T, and NK cells reduced the survival rate and efficacy of the PGA/alum-adjuvanted chimeric protein. Collectively, the vaccination of PGA/alum-adjuvanted chimeric protein induced strong protection efficacy against homologous and heterologous influenza viruses in mice, which suggests that it may be a promising universal influenza vaccine candidate.

An influenza HA stalk reactive polymeric IgA antibody exhibits anti-viral function regulated by binary interaction between HA and the antibody.

IgA antibodies, which are secreted onto the mucosal surface as secretory IgA antibodies (SIgAs), play an important role in preventing influenza virus infection. A recent study reported that anti-hemagglutinin (HA) head-targeting antibodies increase anti-viral functions such as hemagglutination inhibition (HI) and virus neutralization (NT), in addition to HA binding activity (reactivity) via IgA polymerization. However, the functional properties of anti-viral IgA antibodies with mechanisms of action distinct from those of anti-HA head-targeting antibodies remain elusive. Here, we characterized the functional properties of IgG, monomeric IgA, and polymeric IgA anti-HA stalk-binding clones F11 and FI6, and B12 (a low affinity anti-HA stalk clone), as well as Fab-deficient (ΔFab) IgA antibodies. We found that IgA polymerization impacts the functional properties of anti-HA stalk antibodies. Unlike anti-HA head antibodies, the anti-viral functions of anti-HA stalk antibodies were not simply enhanced by IgA polymerization. The data suggest that two modes of binding (Fab paratope-mediated binding to the HA stalk, and IgA Fc glycan-mediated binding to the HA receptor binding site (RBS)) occur during interaction between anti-stalk HA IgA antibodies and HA. In situations where Fab paratope-mediated binding to the HA stalk exceeded IgA Fc glycan-mediated binding to HA RBS, IgA polymerization increased anti-viral functions. By contrast, when IgA Fc glycan-mediated binding to the HA RBS was dominant, anti-viral activity will fall upon IgA polymerization. In summary, the results suggest that coordination between these two independent binding modules determines whether IgA polymerization has a negative or positive effect on the anti-viral functions of anti-HA stalk IgA antibodies.

Obituary

Obituary

High-dose trivalent influenza vaccine: safety and immunogenicity

RESUMENLas personas mayores son uno de los colectivos que más sufren los efectos de la gripe estacional. Aunque la vacuna antigripal es efectiva a la hora de prevenir la infección por el virus de la gripe y sus complicaciones, no resulta tan efectiva en personas de edad avanzada debido al fenómeno de inmunosenescencia asociado a la edad. Desde 2009 existe en EE. UU. una vacuna antigripal trivalente de alta dosis aprobada para la inmunización de personas ≥ 65 años con una concentración de antígeno cuatro veces mayor que la vacuna estándar. Múltiples ensayos clínicos llevados a cabo a lo largo de distintas temporadas, y mediante diferentes metodologías, han demostrado que la vacuna antigripal trivalente de alta dosis no solo es más efectiva, sino que además presenta un perfil de seguridad similar y es más inmunogénica que la vacuna de dosis estándar en la prevención de la gripe y sus complicaciones en personas de avanzada edad. En este documento se hace una revisión de la evidencia científica actual sobre la seguridad e inmunogenicidad de la vacuna antigripal de alta dosis en personas ≥ 65 años, y se incluye información de ensayos clínicos aleatorizados, estudios observacionales con datos de práctica clínica real y revisiones sistemáticas y metaanálisis.

Technical guidelines for seasonal influenza vaccination in China (2020-2021)

Influenza virus infection is a respiratory infectious disease that can seriously affect human health. Influenza viruses can have frequent antigenic variation and changes, which can result in rapid and widespread transmission resulting in annual epidemics and outbreaks in places of public gathering such as schools, kindergartens and nursing homes. According to WHO estimation, seasonal influenza epidemics have caused an annually 3 to 5 million severe cases and 290 000 to 650 000 deaths globally. Pregnant women, young children, the elderly, and persons with chronic illnesses are at high risk for severe illness and death associated with influenza virus infection. Especially, COVID-19 pandemic might co-circulate with other respiratory infectious diseases such as influenza in the coming winter-spring season. Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and complications from infection. Currently, China has licensed trivalent inactivated influenza vaccine (IIV3) which includes split-virus influenza vaccine and subunit vaccine, quadrivalent inactivated influenza vaccine (IIV4) which is split, and trivalent live attenuated influenza vaccine (LAIV3) which was newly licensed. Except for a few major cities, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients must pay for it. In 2018 and 2019, the China CDC issued the "Technical Guidelines for Seasonal Influenza Vaccination in China" . In the past year, new research evidences home and abroad have been published, and new seasonal influenza vaccine has been licensed in China. To strengthen the technical guidance for prevention and control of influenza and operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC) Influenza Vaccination Technical Working Group (TWG), updated the 2019-2020 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2020-2021)" . The main updates in this version include the following: First, new research evidences especially studies of China, including disease burden, effectiveness, Vaccine-avoidable disease burden, vaccine safety monitoring, and cost-effectiveness and cost-benefit. Second, policies and measures for influenza prevention and control issued by National Health Commission (PRC) in the past year. Thirdly, new type seasonal influenza vaccine licensed and issued in 2020-2021 in China. Fourth, northern hemisphere influenza vaccination composition for the 2020-2021 season which included trivalent and quadrivalent influenza vaccine. Fifth, Influenza vaccination recommendations for 2020-2021 influenza season. The recommendations described in this report include the following: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended, and appropriate product is available. Considering the situation of globally pandemic of COVID-19, to decrease the risk of influenza virus infection and minimize the impact on COVID-19 prevention and control, we recommend the following priority for seasonal influenza vaccination: healthcare workers, including clinical doctors and nurses, public health professionals, quarantine professionals; vulnerable groups living in nursing homes or welfare homes and staffs who take care those vulnerable groups; people work or stay in high population density places, such as teachers and students in kindergartens, primary and secondary school, prisoners and staffs of prisons; other high risk group of influenza, including adults ≥60 years of age, children aged 6-59 months, persons with specific chronic diseases, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to become pregnant during the influenza season. Children aged 6 months through 8 years require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. People whoever get IIV or LAIV all apply to the principle. If they were vaccinated in 2019-2020 influenza season or a prior season, 1 dose is recommended. People more than 8 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. For the people unable to be vaccinated before the end of October, influenza vaccination will continue to be offered for the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for use by staff members of the CDCs at all levels who work on influenza control and prevention, PoVs staff members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and staff members of maternity and child care institutions at all levels. These guidelines will be updated periodically as new evidence becomes available.

Technical guidelines for seasonal influenza vaccination in China (2020-2021)

Influenza virus infection is a respiratory infectious disease that can seriously affect human health. Influenza viruses can have frequent antigenic variation and changes, which can result in rapid and widespread transmission resulting in annual epidemics and outbreaks in places of public gathering such as schools, kindergartens and nursing homes. The World Health Organization (WHO) estimated that seasonal influenza epidemics have caused an annual 3 to 5 million severe cases, and 290000 to 650000 deaths globally. Pregnant women, young children, the elderly, and persons with chronic illnesses are at high risk for severe illness and death associated with influenza virus infection. Especially, COVID-19 pandemic might co-circulate with other respiratory infectious diseases such as influenza in the coming winter-spring season. Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and complications from infection. Currently, China has licensed trivalent inactivated influenza vaccine (IIV3) which includes split-virus influenza vaccine and subunit vaccine, quadrivalent inactivated influenza vaccine (IIV4) which is split, and trivalent live attenuated influenza vaccine(LAIV3) which was newly licensed. Except for a few major cities, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients must pay for it. In 2018 and 2019, the Chinese Center for Disease Control and Prevention issued the"Technical Guidelines for Seasonal Influenza Vaccination in China". In the past year, new research evidences home and abroad have been published, and new seasonal influenza vaccine has been licensed in China. To strengthen the technical guidance for prevention and control of influenza and operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC) Influenza Vaccination Technical Working Group (TWG), updated the 2019-2020 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2020-2021)". The main updates in this version include the following: First, new research evidences especially studies of China, including disease burden, effectiveness, Vaccine-avoidable disease burden, vaccine safety monitoring, and cost-effectiveness and cost-benefit. Second, policies and measures for influenza prevention and control issued by National Health Commission(PRC)in the past year. Thirdly, new type seasonal influenza vaccine licensed and issued in 2020-2021 in China. Fourth, northern hemisphere influenza vaccination composition for the 2020-2021 season which included trivalent and quadrivalent influenza vaccine. Fifth, Influenza vaccination recommendations for 2020-2021 influenza season. The recommendations described in this report include the following: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended, and appropriate product is available. Considering the situation of globally pandemic of COVID-19, to decrease the risk of influenza virus infection and minimize the impact on COVID-19 prevention and control, we recommend the following priority for seasonal influenza vaccination: (1) healthcare workers, including clinical doctors and nurses, public health professionals, quarantine professionals; (2) Vulnerable groups living in nursing homes or welfare homes and staffs who take care those vulnerable groups; (3) People in some key places, such as teachers and students in kindergartens, primary and secondary school, prisoners and staffs of prisons; (4) Other high risk group of influenza, including adults ≥60 years of age, children aged 6-59 months, persons with specific chronic diseases, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to become pregnant during the influenza season. Children aged 6 months through 8 years require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. People whoever get IIV or LAIV all apply to the principle. If they were vaccinated in 2019-2020 influenza season or a prior season, 1 dose is recommended. People more than 8 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. For the people unable to be vaccinated before the end of October, influenza vaccination will continue to be offered for the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for use by staff members of the Centers for Disease Control and Prevention at all levels who work on influenza control and prevention, PoVs staff members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and staff members of maternity and child care institutions at all levels. These guidelines will be updated periodically as new evidence becomes available.

Avian Influenza Virus Prevalence and Subtype Diversity in Wild Birds in Shanghai, China, 2016–2018

From 2016 to 2018, surveillance of influenza A viruses in wild birds was conducted in Shanghai, located at the East Asian–Australian flyway, China. A total of 5112 samples from 51 species of wild birds were collected from three different wetlands. The total three-year prevalence of influenza A viruses among them was 8.8%, as assessed using real-time polymerase chain reaction (PCR) methods, and the total prevalence was higher in Anseriformes (26.3%) than in the Charadriiformes (2.3%) and the other orders (2.4%) in the Chongmin wetlands. Anseriformes should be the key monitoring group in future surveillance efforts. The peak prevalence of influenza A viruses in Charadriiformes were in April and September, and in other bird orders, the peaks were in November and December. Twelve subtypes of haemagglutinin (HA; H1–H12) and eight subtypes of neuraminidase (NA; N1, N2, N4–N9) were identified in 21 different combinations. The greatest subtype diversity could be found in common teal, suggesting that this species of the bird might play an important role in the ecology and epidemiology of influenza A viruses in Shanghai. These results will increase our understanding of the ecology and epidemiology of influenza A viruses in wild bird hosts in eastern China, and provide references for subsequent surveillance of influenza A virus in wild birds in this area.

Prevalence and factors influencing the distribution of influenza viruses in Kenya: Seven-year hospital-based surveillance of influenza-like illness (2007-2013).

BackgroundInfluenza viruses remain a global threat with the potential to trigger outbreaks and pandemics. Globally, seasonal influenza viruses’ mortality range from 291 243–645 832 annually, of which 17% occurs in Sub-Saharan Africa. We sought to estimate the overall prevalence of influenza infections in Kenya, identifying factors influencing the distribution of these infections, and describe trends in occurrence from 2007 to 2013.MethodsSurveillance was conducted at eight district hospital sites countrywide. Participants who met the case definition for influenza-like illness were enrolled in the surveillance program. The nasopharyngeal specimens were collected from all participants. We tested all specimens for influenza viruses with quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) assay. Bivariate and multivariate log-binomial regression was performed with a statistically significant level of p<0.005. An administrative map of Kenya was used to locate the geographical distribution of surveillance sites in counties. We visualized the monthly trend of influenza viruses with a graph and chart using exponential smoothing at a damping factor of 0.5 over the study period (2007–2013).ResultsA total of 17446 participants enrolled in the program. The overall prevalence of influenza viruses was 19% (n = 3230), of which 76% (n = 2449) were type A, 21% (n = 669) type B and 3% (n = 112) A/ B coinfection. Of those with type A, 59% (n = 1451) were not subtyped. Seasonal influenza A/H3N2 was found in 48% (n = 475), influenza A/H1N1/pdm 2009 in 43% (n = 434), and seasonal influenza A/ H1N1 in 9% (n = 88) participants. Both genders were represented, whereas a large proportion of participants 55% were ≤1year age. Influenza prevalence was high, 2 times more in other age categories compared to ≤1year age. Category of occupation other than children and school attendees had a high prevalence of influenza virus (p< <0.001). The monthly trends of influenza viruses’ positivity showed no seasonal pattern. Influenza types A and B co-circulated throughout the annual calendar during seven years of the surveillance.ConclusionsInfluenza viruses circulate year-round and occur among children as well as the adult population in Kenya. Occupational and school-based settings showed a higher prevalence of influenza viruses. There were no regular seasonal patterns for influenza viruses.

Functional neuraminidase inhibitor resistance motifs in avian influenza A(H5Nx) viruses

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Past influenza virus pandemics seeded by zoonotic infection by avian influenza viruses (AIV) as well as the increasing number of human infections with AIV have shown the importance of having information about resistance to NAIs by avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we showed that a R292K substitution in H5N6 and H5N2 viruses significantly reduced susceptibility to three licenced NAIs: oseltamivir, zanamivir and peramivir. In contrast the mutations E119V, H274Y and N294S had more variable effects with NAI susceptibility being drug- and strain-specific. We measured the replicative fitness of NAI resistant H5N6 viruses and found that they replicated to comparable or significantly higher titres in primary chicken cells and in embryonated hens’ eggs as compared to wild type - despite the NA activity of the viral neuraminidase proteins being reduced. The R292K and N294S drug resistant H5N6 viruses had single amino acid substitutions in their haemagglutinin (HA): Y98F and A189T, respectively (H3 numbering) which reduced receptor binding properties possibly balancing the reduced NA activity seen. Our results demonstrate that the H5Nx viruses can support drug resistance mutations that confer reduced susceptibility to licenced NAIs and that these H5N6 viruses did not show diminished replicative fitness in avian cell cultures. Our results support the requirement for on-going surveillance of these strains in bird populations to include motifs associated with human drug resistance.

Knowledge, barriers and uptake of influenza vaccine among non-health college students at Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.

Background: Viral influenza, one of the global public health problems is specifically important in Saudi Arabia due to high susceptibility of transmission in hajj and umrah seasons (Islamic pilgrimage to the Mecca), as it has the ability to spread widely to a large proportion, in addition the disease has a higher rate of complications that might lead to death. Vaccination is an important strategy in prevention of viral influenza.Design and methods: The study aimed to describe the association between uptake of influenza vaccine with knowledge as well as identify the barriers that prevent vaccination among Princess Nourah Bint Abdulrahman University (PNU) non-health colleges students. A descriptive cross-sectional study design was undertaken, including 385 students from non-health colleges using a convenience sampling technique. Data was collected using an Arabic self-administered online questionnaire Analysis done by JMP program. IRB approval as well as informed consent were taken.Results: The uptake of the influenza vaccine was 15.3% in the current year and 56.8% in the previous years. No significant association was found between knowledge, and uptake of the vaccine. For the unvaccinated students, the most common encounter barriers stated by study population were concerns regarding the vaccine effectiveness, reduction of immunity the uncertainty of complete protection in a percentage of 12.0% for all.Conclusions: Although the level of vaccine uptake is low for this year, it is not associated with knowledge. There were some barriers that need to be tackled by health education programs.Significance for public healthThe identification of the factors that prevent university students from uptake of the influenza vaccine are essential to maximize vaccine uptake as Influenza continues to cause significant morbidity and mortality in whole world, including Saudi Arabia. Studies exploring influenza vaccine coverage for students are considered important in order to find out the misconception and target it by health education program, which ultimately increase the coverage.

Amide-sialoside protein conjugates as neomucin bioshields prevent influenza virus infection

We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (KD) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin.

E. coli-Produced Monophosphoryl Lipid a Significantly Enhances Protective Immunity of Pandemic H1N1 Vaccine.

Emerging influenza viruses pose an extreme global risk to human health, resulting in an urgent need for effective vaccination against influenza infection. Adjuvants are vital components that can improve vaccine efficacy, yet only a few adjuvants have been licensed in human vaccines. Here, we investigate the adjuvant effects of Escherichia coli-produced monophosphoryl lipid A (MPL), named EcML, in enhancing the immunogenicity and efficacy of an influenza vaccine. Similar to MPL, EcML activated dendritic cells and enhanced the antigen processing of cells in vitro. Using ovalbumin (OVA) as a model antigen, EcML increased OVA-specific antibody production, cytotoxic T lymphocyte activity. The safety of EcML was demonstrated as being similar to that of MPL by showing not significant in vitro cell cytotoxicity but transient systemic inflammatory responses within 24 h in OVA immunized mice. Importantly, mice vaccinated with pandemic H1N1 (pH1N1) vaccine antigen, combined with EcML, were fully protected from pH1N1 virus infection by enhanced influenza-specific antibody titers, hemagglutination inhibition titers, and IFN-γ- secreting cells. Taken together, our results strongly suggest that EcML might be a promising vaccine adjuvant for preventing influenza virus infection.

High-dose trivalent influenza vaccine. Efficacy and effectiveness

RESUMENLa gripe estacional es un importante problema de salud pública, particularmente en las personas mayores. La vacuna antigripal es la forma más efectiva de prevenir la infección por el virus de la gripe y sus complicaciones, pero debido al fenómeno de inmunosenescencia asociado a la edad, las personas mayores no responden eficientemente a la inmunización. En 2009 se aprobó en EE. UU. una vacuna antigripal trivalente de alta dosis (IIV3-HD), con una concentración cuatro veces mayor de antígeno que la vacuna estándar, para la inmunización de personas ≥ 65 años. En numerosos ensayos clínicos llevados a cabo en diferentes temporadas, y utilizando diferentes metodologías, se ha demostrado que la vacuna IIV3-HD es, además de segura, más inmunogénica y más efectiva que la vacuna de dosis estándar previniendo la gripe y sus complicaciones en personas mayores. En este trabajo se hace una revisión de la evidencia científica disponible sobre la eficacia y efectividad de la vacuna antigripal de alta dosis en personas ≥ 65 años, incluyendo información de ensayos clínicos aleatorizados, estudios observacionales de práctica clínica real y revisiones sistemáticas y meta-análisis.