Influenza Virus Research Articles

Multi-Electrode Extended Gate Field Effect Transistors Based on Laser-Induced Graphene for the Detection of Vitamin C and SARS-CoV-2.

Despite the clinical data showing the importance of ascorbic acid (AA or vitamin C) in managing viral respiratory infections, biosensors for their simultaneous detection are lacking. To address this need, we developed a portable and wireless device for simultaneous detection of AA and SARS-CoV-2 virus by integrating commercial transistors with printed laser-induced graphene (LIG) as the extended gate. We studied the effect of laser printing pass number and showed that with two laser printing passes (2-pass LIG), the sensor sensitivity and limit of detection (LOD) for AA improved by a factor of 1.6 and 12.8, respectively. Using complementary characterization methods, we attribute the improved response to a balanced interplay of crystallinity, defect density, surface area, surface roughness, pore density and diameter, and mechanical integrity/stability. These factors enhance analyte transport, reduce noise/variability, and ensure consistent sensor performance, making 2-pass LIG the most effective material in this work. Our sensors exhibit promising performance for detecting AA with a selective response in the presence of common salivary interfering molecules, with sensitivity and LOD of 73.67 mV/dec and 54.04 nM in 1× phosphate buffered saline and 81.05 mV/dec and 78.34 nM in artificial saliva, respectively. We also showed that functionalization of the 2-pass LIG gate with S-protein antibody enables the detection of SARS-CoV-2 protein antigens with an ultralow LOD of 52 zg/mL─an improvement of more than 10-fold compared to 1-pass LIG─and 4 particles/mL for virion mimics with a selective response against influenza virus and multiple human coronavirus strains. With low signal drift/hysteresis and wireless capabilities, the developed device holds great potential for improving at-home monitoring and clinical decision-making.

CXCL13 promotes broad immune responses induced by circular RNA vaccines.

Antibody responses induced by current vaccines for influenza and SARS-CoV-2 often lack robust cross-reactivity. As hubs where diverse immune cells converge and interact, the alterations in the immune microenvironment within lymph nodes (LNs) are intricately linked to immune responses. Herein, we designed a lipid nanoparticle (LNP) loaded with circular RNA (circRNA) and targeted to LNs, in which CXCL13 was directly integrated into antigen-encoding circRNA strands. We demonstrated that CXCL13 alters the transcriptomic profiles of LNs, especially the upregulation of IL-21 and IL-4. Meanwhile, CXCL13 promotes the formation of germinal center and elicits robust antigen-specific T cell responses. With the codelivery of CXCL13 and the antigen, CXCL13 enhances cross-reactive antibodies against influenza virus and SARS-CoV-2, achieving protection against both homologous and heterologous influenza virus challenges in a mouse model. Notably, the targeted modification of LNP surfaces with antibodies helps address some of the challenges associated with lyophilized LNP vaccines, which is crucial for the long-term storage of LNP-circRNA vaccines. Overall, the circRNA-based antigen-CXCL13 coexpression system developed herein provides a simple and robust platform that enhances the magnitude and breadth of antibody responses against multiple viral glycoproteins, highlighting the potential utility of CXCL13 in inducing broad immune responses.

Attitudes, Beliefs, and Self-Reported Rates of Influenza and COVID-19 Vaccinations in the Canadian 2023–2024 National Influenza and Respiratory Viruses Survey

Background: We conducted a cross-sectional, online survey of adult Canadian residents to evaluate their attitudes and beliefs about vaccination against respiratory viruses, particularly influenza and coronavirus 2019 (COVID-19). Methodology: Survey participants aged ≥ 18 years were randomly recruited from the Léger Opinion (LEO) consumer panel. Results: Out of 3002 respondents, 76% reported being “up-to-date” on all of their recommended vaccinations, 86% reported understanding why the influenza vaccine was needed annually, 79% reported believing the influenza vaccine was safe, and 83% reported understanding that vaccines, in general, were important for health. However, only 49% reported receiving the influenza vaccine in the fall of 2023, and 46% received a COVID-19 vaccine (68% of those who received one received the other). More than half of the respondents (55%) reported that they found it difficult to keep track of which vaccines were recommended for them, while 74% indicated that they valued the opinion of their healthcare provider (HCP) when deciding whether to be vaccinated against influenza, and 73% said they would not hesitate to receive multiple vaccines at the same time if their HCP recommended it. Conclusions: These findings highlight the ongoing need for education and outreach in Canada.

Wastewater-Based Epidemiology of Influenza Viruses: a systematic review

Abstract Background Influenza viruses (IVs) are responsible for annual epidemic outbreaks during the winter months. Beyond conventional surveillance systems, the circulation of these pathogens can be monitored using Wastewater-Based Epidemiology (WBE), an epidemiological tool that describes the health status of an entire community by analyzing the presence of pathogens within wastewater. Systematically reviewing existing experiences in this emerging field is crucial to highlight the best practices to establish a WBE surveillance system providing useful information for public health actions. Methods The study protocol for this systematic review has been registered on the PROSPERO website (registration ID: CRD42024532435). Three academic databases (PubMed, Web of Science and Scopus) were accessed to collect studies examining the presence of IVs in wastewater. Studies included were those reporting quantitative measures of viral concentration or detailing molecular/phylogenetic characterization of IVs in wastewater. Results Databases were searched on July 8th, 2024. After de-duplication and screening of the 400 remaining records, 42 were included in the review. IVs detection in wastewater was reported in all papers except from one, although with high variability in terms of positivity titers and concentration levels. More than half of the collected papers (52.4%) evaluated association between environmental viral concentration and clinical data, generally showing concordance between the two aspects. Moreover, 28.6% of papers described subtyping of IVs in wastewater through different methods (specific PCR assays being the most used). Conclusions WBE is a promising approach for surveilling viral circulation, and IVs represent a high value target for implementing this innovative system. Systematically reviewing previous experiences can be useful to obtain information for the establishment of a novel environmental surveillance system of Influenza Viruses Key messages • Nucleic acids belonging to Influenza Virus are detectable in wastewater, even though we report high levels of variability in sampling techniques, laboratory methods and data management systems. • Association between environmental data and number of clinical cases is reported to be generally strong in collected papers; subtyping of IVs present in wastewater is also feasible.

Integrated sentinel surveillance of influenza, SARS-CoV-2, RSV and respiratory viruses in Serbia

Abstract Introduction Integrated sentinel SARI surveillance of influenza, SARS -CoV-2 and RSV has been established in Serbia since 2021-2022 influenza season. Nine sentinel hospitals in 3 cities participated in the SARI surveillance system. The aim of this study is to provide a review of integrated sentinel surveillance of SARI in Serbia in 2023-2024 influenza season, from October 2023 to April 2024. Methods On a weekly basis, both epidemiological and virological data were collected. Surveillance is be conducted year-round. Specimens were tested for influenza, SARS-CoV-2,RSV and other respiratory viruses. Respiratory disease wards, intensive care units (ICUs) and pediatric wards were all represented. Real time polymerase chain reaction (RT-PCR) was used. Results From October 2023 to April 2024, a total of 1571 SARI cases were reported with 100% recorded age. Of these, 35% were 0-4 years old, 16% were 5-14, 6% were 15-29, 14% were 30-64, 18% were 65-79 and 11% were 80+. Among these cases, 1002 (64%) respiratory specimens were collected. The number of positive samples for influenza was 294 (29%). The positivity rate was 10% for SARS-CoV-2 and 19 % for RSV. The highest proportion of laboratory-confirmed influenza cases was 67% in week 04/2023. Then above 50% in week 05/2023 and 06/2023. Type A viruses was predominated, accounting for 97% of all influenza SARI detections. Activity was dominated by A(H3) with 42% positivity rate. Also, collected swabs were tested for rhinoviruses, positivity rate was 26%, for adenoviruses, 12%, for human metapneumovirus, 7% and for parainfluenza 3 viruses, 4%. Conclusions Sustaining and intensified effective integrated surveillance for influenza, SARS-CoV-2,RSV and other respiratory viruses in Serbia is the priority especially in the frame of International Health Regulations. In this way, we improve national capacity for preparedness and emergency response to national and cross-border public health threats. Key messages • Building and maintaining integrated respiratory surveillance that can rapidly integrate the surveillance of a new viruses is crucial. • Establishing well structured surveillance of severe acute respiratory infections, strengthening and expanding respiratory viral surveillance is one the base pillars preparation for future pandemics.

Introduction of wastewater surveillance of SARS-CoV-2 in Ukraine

Abstract Since the Russian invasion, Ukraine has faced humanitarian crises and challenges in diseases surveillance. The primary healthcare (PHC) system struggled with growing numbers of internally displaced and wounded people. In October 2022, the PATH-led, USAID-funded Support TB Control Efforts in Ukraine (STBCEU) project, supported implementation of wastewater surveillance (WWS) for SARS-CoV-2 in four oblasts on request of the Ministry of Health (MoH), expanding to 18 oblasts by October 2023. Samples were collected from 64 sites twice per week and tested for SARS-CoV-2 and influenza A/B using BioExtract® Premium Mag test kits in regional laboratories. From October 2022 to April 2024, 4,784 samples were collected at municipal aqueducts, with SARS-CoV-2 delta and omicron variants detected across all regions. WWS sample results were compared with routine surveillance to assess trends in concentrations and reported cases among population. Gradual decrease in SARS-CoV-2 concentration to zero by May 29, 2023, coincided with a decrease in morbidity. In the last week of August 2023, the concentration of the SARS-CoV-2 in wastewater began its gradual increase with the beginning of new cases registration among the population within 2 weeks, by mid-September. From October 2023, SARS-CoV-2 dominated in 96.6% of positive WWS testing results; in other specimens, influenza and respiratory viruses have been identified. The implementation of WWS in Ukraine highlighted its effectiveness as a public health tool in settings where traditional surveillance methods are disrupted, providing timely data on the viral pathogens for outbreaks prediction and responses, underscoring its role in preventive health measures. The MOH of Ukraine recommended extending the method nationwide for routine surveillance of SARS-CoV-2 and other pathogens, enhancing Ukraine’s capacity to manage public health threats and strengthen the resilience of its health system against future crises. Key messages • WWS in Ukraine underscores its effectiveness as a public health tool, providing timely data on viral pathogens for outbreak prediction and response in disrupted settings. • Notable decline in SARS-CoV-2 concentration in wastewater correlates with reduced morbidity, highlighting WWS’s predictive value.

Main challenges and measures taken by public health institutions in response to war in Kyiv Region

Abstract Background The establishment of martial law due to Russia’s military aggression against Ukraine led to specific adjustments in the functioning of the Centers for Diseases Control and Prevention (СDС). The negative impact of hostilities is determined by the increased morbidity rate of communicable and non-communicable diseases, insufficient supply of safe drinking water and food to damaged sites, inadequate living conditions, etc. Objectives The purpose of the work was to create an effective system for responding to biological, chemical and radiation hazards and eliminating the consequences of an emergency situation in the realities of martial law. Methods We used the most common methods, namely descriptive, statistical, microbiological and сhemical laboratory tests. Results The activities of the CDC under martial law include daily monitoring studies of environmental objects. The epidemic situation of acute intestinal infection (AII) and other communicable diseases (CD) is constantly analyzed. The Kyiv Oblast CDC became the basic institution for the implementation of the ‘pilot project’ in the direction of sanitary and epidemic assessment and monitoring of environmetal objects in 188 de-occupied areas. The main public health risks were identified: providing the population with high-quality drinking water; low immunization rate of the population; sites for the location of internally displaced persons; natural foci of especially dangerous diseases, such as tularemia, leptospirosis, infection fevers, etc. In 2022, the overall level of CD in the Kyiv region decreased by 44.0% from 2021. The most common nosologies were acute respiratory viral infections and influenza (98.9%), AII (42.4%), tuberculosis (15.3%), Lyme disease (15.3%), and viral hepatitis (14.2%). Conclusions Based on the research conducted, mechanisms have been developed for responding to hazards of various origins by public health institutions, including risk assessmant and laboratory studies. Key messages • The main focus of the Centers for Diseases Control and Prevention is aimed at effective response to hazards of various origins in order to ensure public health under martial law. • Risk assessment in de-occupied territories has become an important tool for identifying correct approaches to prevent negative consequences for public health.

Excess mortality and hospitalizations associated with seasonal influenza in patients with heart failure

Abstract Background Influenza virus may cause severe infection in patients with heart failure. It is accepted that influenza infection is associated with increased morbidity and mortality in patients with heart failure. However, less is known about the excess burden of morbidity and mortality caused by influenza infection in patients with heart failure at a population level. Purpose To estimate the excess burden of morbidity and mortality as determined by annual excess number of deaths and hospitalizations associated with influenza infection in patients with heart failure. Methods We collected nationwide data on weekly number of deaths and hospitalizations among patents with heart failure in Denmark and weekly estimates of influenza circulation as determined by the proportion of positive influenza samples analyzed at all Danish Hospitals. These data were correlated in a time series linear regression model and this model was used to estimate the annual excess number of deaths and hospitalizations attributable to influenza circulation among patients with heart failure in Denmark. Results Data were available from 2010 to 2018 encompassing 8 influenza seasons with an annual mean of 25180 samples tested for influenza. Among an annual mean of 70570 patients with heart failure, our model estimated that influenza activity was associated with an annual excess of 250 all cause deaths (95%CI 144-489) corresponding to 2.6% of all all-cause deaths (95%CI 1.5% - 5.1%). Similarly, influenza activity was associated with an annual excess of 115 cardiovascular deaths (95%CI 62-244) corresponding to 2.9% of all cardiovascular deaths (95%CI 1.5% - 6.1%) among patients with heart failure. Influenza activity was also associated with an annual excess of 251 hospitalizations for pneumonia or influenza (95%CI 107-533) corresponding to 5.0% of all hospitalizations for pneumonia or influenza. Conclusion Our results indicate that influenza activity likely causes substantial morbidity and mortality among patients with heart failure. Notably, our study suggests that approximately 2.6% of all deaths and 5.0% of all hospitalizations with influenza or pneumonia may be attributed to influenza in patients with heart failure.

A human isolate of bovine H5N1 is transmissible and lethal in animal models.

The outbreak of clade 2.3.4.4b highly pathogenic avian influenza viruses of the H5N1 subtype (HPAI H5N1) in dairy cows in the US has so far resulted in spillover infections of at least thirteen farm workers1-3, who presented with mild respiratory symptoms or conjunctivitis, and one individual with no known animal exposure who was hospitalized but recovered3,4. Here, we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis5. huTX37-H5N1 replicated efficiently in primary human alveolar epithelial cells, but less efficiently in corneal epithelial cells. Despite causing mild disease in the infected worker, huTX37-H5N1 was lethal in mice and ferrets and spread systemically with high titres in respiratory and non-respiratory organs. Importantly, in four independent experiments in ferrets, huTX37-H5N1 transmitted via respiratory droplets in 17%-33% of transmission pairs and five of six exposed ferrets that became infected died. PB2-631L (encoded by bovine isolates), promoted influenza polymerase activity in human cells, suggesting a role in mammalian adaptation like that of PB2-627K (encoded by huTX37-H5N1). Additionally, bovine HPAI H5N1 viruses were found to be susceptible to polymerase inhibitors both in vitro and in mice. Thus, HPAI H5N1 virus derived from dairy cattle transmits by respiratory droplets in mammals without prior adaptation and causes lethal disease in animal models.

The effects of weather and mobility on respiratory viruses before and during the COVID-19 pandemic

Abstract Background The flu season is caused by a combination of different pathogens, including influenza viruses, which cause the flu, and non-influenza respiratory viruses, that cause common colds or influenza-like illness. These viruses exhibit similar dynamics and, given that outbreaks occur mostly in the winter and there is almost no circulation during the summer, in temperate regions, meteorological conditions have historically been regarded as a principal modulator of their epidemiology. However, after the emergence of SARS-CoV2, in late 2019, the dynamics of these respiratory viruses were strongly perturbed worldwide: some infections displayed near-eradication, while others experienced temporal shifts or occurred “off-season”. This disruption raised questions regarding the dominant role of weather while also providing an unique opportunity to investigate the roles of other determinants in their epidemiological dynamics. Methods Weather, mobility and epidemiological surveillance data was collected for Influenza, RSV, hCOV and hMPV, from Canada and the USA, from 2016 to 2023. Statistical analysis and modeling were employed to test the effects of weather and mobility on viral dynamics, before and during the COVID-19 pandemic. Results Using Beta Regressions, we found that whereas in the pre-COVID-19 pandemic period, weather had a strong effect, in the pandemic period, this effect was strongly reduced post-pandemic with mobility playing a more significant role. Conclusions These results, together with previous studies, dispute the general belief that respiratory viral dynamics are mostly dictated by weather and indicate that behavioral changes resulting from the non-pharmacological interventions implemented to control SARS-CoV2, played a key role. This disruption of past dynamical equilibrium raises important questions regarding the factors that modulate them, particularly in a context of climate change. Key messages • We took advantage of the disruption caused by COVID-19 to study dynamics of other respiratory viruses and to disentangle the effects of weather from those of human behavior. • While before 2020 cold temperatures were highly correlated with incidence, afterwards cold weather was no longer a necessary condition and human mobility became central.

Combating Emerging Respiratory Viruses: Lessons and Future Antiviral Strategies

Emerging viral diseases, including seasonal illnesses and pandemics, pose significant global public health risks. Respiratory viruses, particularly coronaviruses and influenza viruses, are associated with high morbidity and mortality, imposing substantial socioeconomic burdens. This review focuses on the current landscape of respiratory viruses, particularly influenza and SARS-CoV-2, and their antiviral treatments. It also discusses the potential for pandemics and the development of new antiviral vaccines and therapies, drawing lessons from past outbreaks to inform future strategies for managing viral threats.

Three-strain epidemic model for influenza virus involving fractional derivative and treatment

Three-strain epidemic model for influenza virus involving fractional derivative and treatment

Monitoring the Cascade of Monocyte-Derived Macrophages to Influenza Virus Infection in Human Alveolus Chips.

Respiratory viruses ravage the world and seriously threaten people's health. Despite intense research efforts, the immune mechanism underlying respiratory virus-induced acute lung injury (ALI) and pulmonary fibrosis (PF) has not been fully elucidated. Here, the cascade of monocyte-derived macrophages to influenza A virus infection is monitored on an optimized human alveolus chip to reveal the role of macrophages in the development of ALI and PF. We find that viral infection causes damage to the alveolar air-liquid barrier and the release of inflammatory cytokines, which induce the M0 macrophages to gather and polarize to the M1 phenotype at the damaged site through recruitment, adhesion, migration, and activation, leading to ALI. Afterward, M1 macrophages polarize into the M2 phenotype, and then transform into myofibroblasts, followed by enhanced secretion of various anti-inflammatory cytokines and profibrotic cytokines, to promote PF. Our study provides an insight into the pathogenesis of virus-induced ALI and PF, which will assist in the development of therapeutic strategies and drugs for treating influenza and other respiratory virus infections.

Fight the Flu: Protect Yourself and Others

As flu season approaches, it's crucial to take steps to protect yourself and those around you. The flu, a contagious respiratory illness caused by the influenza virus, can lead to severe complications, especially in young children, the elderly, and those with weakened immune systems. The best defense against the flu is vaccination. Flu vaccines are updated yearly to match circulating strains, reducing your chances of getting sick. Even if you catch the flu, the vaccine can lessen the severity of symptoms and prevent hospitalization. Different types of vaccines, such as standard-dose, high-dose, and adjuvanted vaccines, are tailored for various age groups, including children, adults, and seniors. In addition to vaccination, practicing good hygiene, like frequent handwashing, covering coughs, and staying home if sick, plays a crucial role in flu prevention. Together, these strategies form a strong defense against the flu, safeguarding communities during flu season.

Evaluation of the preventive effectiveness of russian influenza vaccines in the epidemic seasons of 2018-2021

Monitoring the effectiveness of influenza vaccines annually enables the development of measures aimed at decreasing influenza incidence, hospitalization, and mortality rates. The epidemiological effectiveness of several Russian domestic influenza vaccines was evaluated in St. Petersburg in the 2018-2021 epidemic seasons. Male and female participants (N = 6912) aged 18-23 were monitored from 2018 to 2021. Sovigripp, Grippol Plus, Ultrix, and Ultrix Quadri inactivated influenza vaccines were used for immunization. In 2018-2019, when the vaccine strains fully matched the circulating influenza viruses, prophylactic vaccination resulted in a 2.7 to 7.1-fold reduction in influenza cases. The protective effectiveness of the vaccines against influenza and acute respiratory infections (ARIs) totalled 52.4%, reaching 73.0% effectiveness against influenza after laboratory confirmation. In the epidemic season 2019-2020, when the circulating viruses and vaccine strains did not fully match, the incidence of influenza and ARIs reduced twice due to vaccination; the total vaccine effectiveness against influenza and ARIs amounted to 50.0%. The Grippol Plus, Ultrix, and Ultrix Quadri vaccines proved to be the most effective, demonstrating a total effectiveness of 70.6%-75.0% and a 65.5%-83.5% effectiveness against influenza A and B. In the 2020-2021 epidemic season, no data on the preventive effectiveness of the influenza vaccines could be obtained due to the outbreak of COVID-19 and the absence of detectable influenza virus shedding in the study participants. The results obtained are consistent with WHO experts’ estimates which indicate that modern influenza vaccines reduce the incidence of influenza in adults by 70-90% if the vaccine strains match the circulating virus strains.

Structural and free energy landscape analysis for the discovery of antiviral compounds targeting the cap-binding domain of influenza polymerase PB2

Influenza poses a significant threat to global health, with the ability to cause severe epidemics and pandemics. The polymerase basic protein 2 (PB2) of the influenza virus plays a crucial role in the viral replication process, making the CAP-binding domain of PB2 an attractive target for antiviral drug development. This study aimed to identify and evaluate potential inhibitors of the influenza polymerase PB2 CAP-binding domain using computational drug discovery methods. We employed a comprehensive computational approach involving virtual screening, molecular docking, and 500 ns molecular dynamics (MD) simulations. Compounds were selected from the Diverse lib database and assessed for their binding affinity and stability in interaction with the PB2 CAP-binding domain. The study utilized the generalized amber force field (GAFF) for MD simulations to further evaluate the dynamic behaviour and stability of the interactions. Among the screened compounds, compounds 1, 3, and 4 showed promising binding affinities. Compound 4 demonstrated the highest binding stability and the most favourable free energy profile, indicating strong and consistent interaction with the target domain. Compound 3 displayed moderate stability with dynamic conformational changes, while Compound 1 maintained robust interactions throughout the simulations. Comparative analyses of these compounds against a control compound highlighted their potential efficacy. Compound 4 emerged as the most promising inhibitor, with substantial stability and strong binding affinity to the PB2 CAP-binding domain. These findings suggest that compound 4, along with compounds 1 and 3, holds the potential for further development into effective antiviral agents against influenza. Future studies should focus on experimental validation of these compounds and exploration of resistance mechanisms to enhance their therapeutic utility.

Developing Correlates of Protection for Vaccines Is Needed More than Ever—Influenza, COVID-19 and RSV Infection

One of the greatest success stories of modern medicine is the prevention of infectious diseases by vaccination, most notably against smallpox and poliomyelitis. However, recent events, such as the 2009–2010 swine flu and the 2020 COVID-19 pandemics, as well as the continued emergence of highly pathogenic avian influenza viruses highlighted the fact that we still need to develop new vaccines, and perhaps we should be proactive, rather than reacting to epidemics and pandemics. However, the development of tools for evaluating novel vaccines has not been able to keep up with the rate of vaccine production. Humoral and cellular immune responses to vaccination have both been suggested to be important in preventing infections or ameliorating their consequences, although there is uncertainty regarding their exact roles and importance. This, together with the rapid development of new vaccines, means that the need for developing immunogenicity parameters, and even more importantly, reliable correlates of protection, is more important than ever.

Designing a multi-epitope influenza vaccine: an immunoinformatics approach

Influenza continues to be one of the top public health problems since it creates annual epidemics and can start a worldwide pandemic. The virus’s rapid evolution allows the virus to evade the host defense, and then seasonal vaccines need to be reformulated nearly annually. However, it takes almost half a year for the influenza vaccine to become accessible. This delay is especially concerning in the event of a pandemic breakout. By producing the vaccine through reverse vaccinology and phage display vaccines, this time can be reduced. In this study, epitopes of B lymphocytes, cytotoxic T lymphocytes, and helper T lymphocytes of HA, NA, NP, and M2 proteins from two strains of Influenza A were anticipated. We found two proper epitopes (ASFIYNGRL and LHLILWITDRLFFKC) in Influenza virus proteins for CTL and HTL cells, respectively. Optimal epitopes and linkers in silico were cloned into the N-terminal end of M13 protein III (pIII) to create a multi-epitope-pIII construct, i.e., phage display vaccine. Also, prediction of tertiary structure, molecular docking, molecular dynamics simulation, and immune simulation were performed and showed that the designed multi-epitope vaccine can bind to the receptors and stimulate the immune system response.

Influenza Vaccine Effectiveness Against Illness and Asymptomatic Infection in 2022-2023: A Prospective Cohort Study.

Previous estimates of vaccine effectiveness (VE) against asymptomatic influenza virus infection based on seroconversion have varied widely and may be biased. We estimated 2022-2023 influenza VE against illness and asymptomatic infection in a prospective cohort. In the HEROES-RECOVER cohort, adults at increased occupational risk of influenza exposure across 7 US sites provided weekly symptom reports and nasal swabs for reverse transcription-polymerase chain reaction (RT-PCR) influenza testing. Laboratory-confirmed influenza virus infections were classified as symptomatic (≥1 symptom) or asymptomatic during the week of testing. Participants reported demographic information and vaccination through surveys; most sites verified vaccination through medical record and immunization registry review. Person-time was calculated as days from the site-specific influenza season start (September-October 2022) through date of infection, study withdrawal, or season end (May 2023). We compared influenza incidence among vaccinated versus unvaccinated participants overall, by symptom status, and by influenza A subtype, using Cox proportional hazards regression adjusted for site and occupation. We estimated VE as (1 - adjusted hazard ratio) × 100%. In total, 269 of 3785 (7.1%) participants had laboratory-confirmed influenza, including 263 (98%) influenza A virus infections and 201 (75%) symptomatic illnesses. Incidence of laboratory-confirmed influenza illness among vaccinated versus unvaccinated participants was 23.7 and 33.2 episodes per 100 000 person-days, respectively (VE: 38%; 95% CI: 15%-55%). Incidence of asymptomatic influenza virus infection was 8.0 versus 11.6 per 100 000 (VE: 13%; 95% CI: -47%, 49%). Vaccination reduced incidence of symptomatic but not asymptomatic influenza virus infection, suggesting that influenza vaccination attenuates progression from infection to illness.

Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models

Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza.