Influenza

This is a Phase 1, randomized, controlled, dose-ranging clinical trial to assess the safety and immunogenicity of novel influenza A Group 1 and influenza A Group 2 mRNA chimeric hemagglutinin (HA) vaccine candidates given as intramuscular injections alone and in combination. A total of 60 healthy men and non-pregnant, non-breastfeeding women aged 18 through 59 years will be enrolled in one of 6 study arms. The 6 arms will consist of: 1) Sequential influenza A Group 1 mRNA chimeric hemagglutinin: cH8/1 (25 µg) followed by cH5/1 (25 µg), 2) Sequential influenza A Group 2 mRNA chimeric hemagglutinin: cH15/3 (25 µg) followed by cH4/3 (25 µg), 3) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (25 µg) followed by cH5/1 + cH4/3 (25 µg), 4) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by placebo, 5) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH5/1 + cH4/3 (50 µg) followed by placebo, 6) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by cH5/1 + cH4/3 (50 µg). The primary objectives are to evaluate safety and immunogenicity: 1) To assess the safety and reactogenicity of one or two doses of monovalent or bivalent Group 1 and 2 study products and 2) To describe the Group 1 and 2 anti-HA stalk IgG antibody responses of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA.

Background: Influenza (flu) infections are a serious global health threat. Each year, between 3 and 5 million people get the flu, and up to 500,000 die from it. Current vaccines protect against seasonal flus, but broader vaccines are needed to protect against potential flu pandemics. Objective: To test an experimental flu vaccine. Eligibility: Healthy people aged 18 to 55 years. Design: The study will last 5 to 8 months and has 2 phases, A and B. The study vaccine will be given either as a shot in the arm or as a nasal spray. Participants will receive 1 of 3 combinations: (1) study vaccine in the nose and placebo in the arm; (2) placebo in the nose and study vaccine in the arm; or (3) placebo in the nose and placebo in the arm. A placebo is just like the real vaccine but contains no active ingredients. Phase A: Participants will have 5 clinic visits over 56 days. They will receive a shot and a nasal spray at 2 of the visits, 28 days apart. At each visit, they will have a physical exam, with tests of their blood, urine, and nasal secretions. They will check their temperature at home and record any symptoms for 7 days after each vaccine. Phase B: Participants will stay in the hospital for at least 9 days. They will be infected with a flu virus. They will provide blood, urine, and nasal fluid samples. They will have tests of their heart function. They will remain in the hospital until they test negative for the flu 2 days in a row. They will have 2 follow-up visits, 4 and 8 weeks after leaving the hospital. ...

The study aims to evaluate an egg-based H5N8 influenza vaccine up to 3 dose levels (low, medium, and high dose) given with or without adjuvant to see if the adjuvant improves vaccine effectiveness. The study will enroll healthy adults aged 18 years and over. Participants will receive 2 injections in their arm of either one of the 3 dose levels of the study vaccine (low, medium, or high dose) with the adjuvant or the unadjuvanted vaccine (high dose). Study duration per participant: approximately 14 months (including screening visit).

Background: * The Laboratory of Infectious Diseases (LID) Clinical Studies Unit (CSU) enrolls healthy volunteers into clinical studies to study infectious diseases. * Viruses can be highly infectious and contagious. They cause considerable illness in the United States each year and a good example of this is influenza (the flu). The LID CSU performs clinical studies to learn about these viral infections and assist in the development of vaccines and treatments for the infections. These clinical studies include influenza "challenge studies" as well as natural history studies and phase I trials involving vaccines for viruses carried by mosquitos such as Zika or Dengue virus. * In influenza challenge studies studies, doctors expose a person to a flu virus. Then they study the flu through the body's natural healing process. This information will help to find better ways to prevent the flu and may also improve treatments for the flu. * Natural history studies and phase I trials of new vaccines are performed so the researchers can learn how some viral infections occur and if new vaccines are safe and potentially effective in preventing the infections. In some of these studies, participants experience insect bites with special clean (non-infected) insects (such as mosquitos) to better understand the role of insects in these infections. Objectives: \- To screen healthy volunteers for future CSU studies. Eligibility: \- Healthy people between the ages of 18 and 65 Design: * The 3- to 5-hour screening exam includes the following: * Medical history and physical exam * Standard blood tests including pregnancy, Hepatitis B and C, and HIV tests * Standard urine drug testing * Electrocardiogram (ECG) to test heart rhythm and function * Chest x-ray * Eligible volunteers are enrolled in the study for up to 1 year, until they take part in a CSU study or are found to be ineligible to participate. * Volunteers may withdraw from the study pool at any time.

Background: Respiratory viruses, like the flu or COVID-19, cause significant illness and death worldwide. Researchers want to collect samples from people with respiratory virus infections. The samples in this natural history study will be used in future research. Objective: To obtain samples from people with respiratory viruses to learn more about respiratory virus infections and the immune responses against them. Eligibility: People aged 3 and older who have or are suspected to have a respiratory virus infection. Design: Participants will be screened with a medical record review. Participants will give blood samples. Data from their medical records will be collected. Participants will give nose samples. A soft plastic strip will be put into each nostril for a minute. They may also give nose, mouth (back of the throat), or saliva samples using swabs. Participants may receive kits by mail to collect nose and blood samples at home. They will use soft plastic strips to collect nose samples. To collect blood, they will prick their finger and dab a few drops of blood on four plastic tips. If a participant is in the hospital, air samples may be collected in their room. Participation will last for up to 2 years. After 2 years, participants may be asked for their consent again to give new samples and new medical data.

Background and rationale:The World Health Organisation (WHO), estimates influenza global deaths at 290,000 to 650,000 annually. Although influenza is mostly associated with upper respiratory tract infections (URTIs), its role in lower respiratory tract infections (LRTIs) and the associated poor clinical outcomes have been overlooked in sub-Saharan Africa. A study conducted in eight SSA countries estimated that 8.2% of cases and 2.8% of deaths from LRTIs were due to primary infection with influenza. Pneumonia and influenza-associated illness are responsible for 8.5% of respiratory deaths in Zambia. However, in routine practice, testing to distinguish between bacterial and viral etiology of RTIs is seldom done outside sentinel surveillance due to the high cost and lack of available testing options. This consequently underestimates viral RTIs in the population. It is particularly important to diagnose flu early on in vulnerable populations so that they receive timely and appropriate medical care. Although Zambia is a high HIV burden country with a prevalence of 11%, there is presently no study that has described the burden of influenza in the HIV positive population. This research study will address gaps in current scientific knowledge, providing key insights about the prevalence, circulating types, seasonality and associated clinical outcomes of influenza, RSV and SARS-CoV-2 infection in Zambia in the post COVID-19 era. Objectives Primary To determine the prevalence of influenza (A and/or B) infections in a high HIV burden setting in Lusaka, Zambia over one or more influenza seasons. Secondary 1. To determine the prevalence of influenza co-infection with RSV and/or SARS-CoV-2 2. To determine the clinical outcomes of influenza (A and/or B) infection among Zambian adults, with and without co-infection with RSV and COVID-19, by HIV and COVID-19 vaccination status. 3. To evaluate the accuracy and yield of aerosol-based sampling for diagnosis of respiratory viruses (influenza, SARS-CoV-2, and RSV) compared to nasal/ nasopharyngeal swabs, for rapid diagnosis of infection among symptomatic individuals in Zambia. 4. To evaluate the acceptability of exhaled breath aerosol (XBA) sampling for diagnosis and screening of respiratory infections of pandemic potential. Study design and participants: Primary objective and secondary objective 1: Cross sectional surveillance study of individuals presenting with flu-like symptoms at two first level hospitals in Lusaka, Zambia. Recruitment of 594 participants will be done over the study period and participants will include both males and females presenting with 2-7 days of flu-like symptoms, able to provide informed consent, aged ≥18 years, with a known HIV status or willing to be tested, with a known COVID 19 vaccination status and available for symptom follow-up. Secondary objective 2: Prospective follow up of participants enrolled in aim 1 for 14 days will be done to document clinical symptom progression and outcomes. Appropriate care will be provided to all participants within routine care services. Secondary objective 3 \& 4: Mixed methods approach. All patients enrolled under aim 1 will be requested to provide in addition to the routine nasopharyngeal sample, an aerosol-based sample for diagnostic accuracy and yield evaluation. We will also conduct an investigator-administered questionnaire to ascertain end-user experience and preferences for either sampling method. Location Zambia (Kanyama and Chawama sub-districts) Duration April 2025 to November 2026 (Participant enrolment duration)

This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose inactivated influenza vaccine (HD-IIV4) in preventing polymerase chain reaction (PCR)-confirmed influenza and influenza-related outcomes in adults ≥65 years of age during the 2023/24, 2024/25, and 2026/27 influenza seasons. The study is an observational study conducted at Kaiser Permanente Northern California (KPNC), an integrated health care system in the United States.

Every year in the fall and winter, numerous respiratory viruses (such as influenza viruses, SARS-CoV-2 (COVID-19), RSV, rhinovirus, and metapneumovirus) circulate in mainland France, causing acute respiratory infections (ARIs). These viruses can cause epidemics of varying severity, requiring close monitoring to determine their circulation levels and adapt public health measures accordingly. In France, ARI surveillance relies on two networks: the Sentinelles network in primary care and the RENAL network in hospitals. The Sentinelles surveillance is conducted in collaboration with Santé publique France, the National Reference Center for Respiratory Infection Viruses (Institut Pasteur and Hospices Civils de Lyon), and the University of Corsica. As part of the virological surveillance of ARIs, Sentinelles physicians are asked to collect nasopharyngeal swabs or saliva samples from a sample of patients presenting with an ARI during their clinic visits. This surveillance makes it possible to identify respiratory viruses circulating in primary care (general practice and pediatrics), to describe confirmed cases for each of the circulating viruses, and to estimate the impact of each on general practice. This surveillance also allows for the evaluation of the effectiveness of vaccines against influenza and COVID-19.

This randomized controlled trial evaluates and compares the immunogenicity of three different influenza vaccine formulations: high-dose trivalent (HD-IIV3), MF59-adjuvanted quadrivalent (aIIV4), and standard-dose trivalent (SD-IIV3) vaccines. The study population consists of patients with hematologic malignancies, including those undergoing autologous stem cell transplantation or CAR-T cell therapy. The primary goal is to identify which vaccine strategy elicits the most robust antibody and T cell-mediated immune responses in this severely immunocompromised population

This protocol describes a clinical trial to develop and validate a Controlled Human Infection Model (CHIM) for influenza A/Arkansas/08/2020 (pH1N1). The study is designed to determine the optimal infectious dose of the pH1N1 challenge strain for use in future clinical trials evaluating influenza countermeasures. The study will enroll and challenge adult volunteers with the pH1N1 influenza virus challenge or sham inoculations. Given the adaptive design of this trial, the potential number of participants can vary. Depending on the pathway recommended by the PSRT and followed in the Trial Schema, the study population can range from around 30 to 99. The anticipated final sample size will be approximately 90 receiving pH1N1 challenge product plus and 6 persons receiving a sham inoculation. Participants will be pre-screened for health and for serological HAI antibody titers of \</1:40 against the challenge strain. Eligible participants will be enrolled sequentially into challenge cohorts and will be randomly assigned to receive a single dose of either sham inoculation or the interventional study product at a dose between 10\^6 to 10\^7 TCID50 (or 10\^5 TCID50 if needed). Dose titration will be conducted under an adaptive escalation schedule whereby dosing will start at 10\^6 TCID50 and escalate to the next dose if a pre-determined symptomatic influenza attack rate and clinical symptom score thresholds are not met and if the dose is determined to be safe with no pre-defined halting criteria being met. The primary objectives of this study are to determine the optimal infectious dose of a pH1N1 viral challenge to cause laboratory-confirmed clinical influenza and to assess the safety profile of pH1N1 viral challenge.

This phase II trial studies the effect of baloxavir in combination with oseltamivir in treating severe influenza infection in patients who have previously received a hematopoietic (blood) stem cell transplant or have a hematological malignancy. Baloxavir is an antiviral drug that inhibits the growth of influenza virus, reduces viral load and prevents further influenza infection. Osetamivir is an antiviral drug that blocks enzymes on the surfaces of influenza viruses, interfering with cell release of complete viral particles. Giving baloxavir in combination with oseltamivir may shorten or decrease the intensity of influenza infection compared to oseltamivir alone.

This randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of Onradivir Tablets in participants aged 12 to 17 years with influenza A virus infection. The trial plans to enroll approximately 150 adolescent participants (12-17 years) with uncomplicated influenza A, confirmed by rapid antigen/nucleic acid testing and within 48 hours of symptom onset. Eligible participants who meet the inclusion criteria and do not meet any exclusion criteria will be randomized in a 2:1 ratio to receive either Onradivir Tablets or placebo once daily for 5 consecutive days. The study consists of a screening period, a treatment period, and a safety follow-up period. Each participant will be followed up until Day 14 after the first dose. Nasopharyngeal swabs will be collected at screening, Day 2, Day 4, Day 5, and Day 10 for virological testing, including: Viral load measurement by reverse transcription quantitative polymerase chain reaction (RT-qPCR) Viral titer determination by culture assay (50% tissue culture infectious dose, TCID₅₀) Throughout the treatment and safety follow-up periods, participants will record body temperature, influenza symptom scores, and daily activity scores using a diary card. Clinical laboratory tests will be performed at screening, Day 5, and Day 15. Physical examinations and vital signs measurements will be conducted at each follow-up visit. Adverse events and concomitant medications will be documented throughout the study.

The goal of this experimental study is to understand if endotracheal tube (ETT) suctioning increases pain and causes stress on the body in intubated adult ICU patients. These patients are already on ventilators, which means they need suctioning to keep their airways clear, but this procedure may be uncomfortable and cause stress. The main questions this study aims to answer are: Does ETT suctioning raise pain levels as measured by the Critical-Care Pain Observation Tool (CPOT)? Does ETT suctioning increase certain chemicals in the blood (hypoxanthine, xanthine, and uric acid) that show stress and lack of oxygen in the body? Researchers will compare patients who have ETT suctioning (intervention group) with those who do not have suctioning during the study period (control group) to see if there are differences in pain and blood markers of stress. Participants will: Have pain measured before and after suctioning using the CPOT. Have blood samples taken from an existing line at three time points: 5 minutes before, 5 minutes after, and 30 minutes after suctioning. Provide demographic information (like age, gender, and diagnosis) from medical records. This research will help improve how pain is managed for ICU patients who cannot speak for themselves, potentially leading to better pain relief methods in the future.

Background: Respiratory viruses circulate throughout the year and around the globe. Wearable and sensor devices, like smartwatches, may be able to help monitor infectious diseases. Researchers want to use them to learn how respiratory viruses affect people in different ways. Objective: To use digital devices to collect data from participants in challenge studies that could indicate subtle changes in health during an infection that might otherwise go unnoticed. Eligibility: Healthy adults who have enrolled, were recently enrolled, or are scheduled to enroll in a challenge study. Design: Participants will stay at NIH for the duration of the challenge study (at least 9 days) and then will have outpatient follow-up visits (2-4). While at NIH, participants will wear a smartwatch at all times. It will record data like temperature, heart rate, breathing rate, and movements. Participants will have a smartphone that records at all times to listen for coughing and changes in voice. Participants will perform tasks every 4 hours during the daytime. They will record themselves coughing, breathing in deeply, and reading aloud. They will take videos of their face. They will play a game to test their reflexes and focus. They will measure their head temperature with their smartwatch. For outpatient visits, participants will use one smartphone and the smartwatch to complete the above tasks. Participants will be sent a smartwatch to wear at home at night to collect additional healthy data. Participation will last the duration of each challenge study, and may range from 10 weeks to 2 years.

This study aims to evaluate the safety and pharmacokinetic profile of the active ingredients Ingavirin forte, capsules, 90 mg + 20 mg (Valenta Pharm JSC, Russia) relative to single-entity Drug Ingavirin, capsules, 90 mg following administration under fasting and fed conditions.

The purpose of trial is to determine if daily usage of a photobiomodulation device will decrease the incidence of upper respiratory tract infections (URI) due to COVID, influenza or other viruses.The RD-X10 device is handheld, can be self-administered, and has been shown to be safe in invivo studies.

A randomized, double-blind, placebo-controlled Phase 1 study conducted at a single center with approximately 78 healthy adults aged 18-59 years. Part 1 Single Ascending Dose (SAD) will enroll 48 participants into six cohorts (S1-S6) to receive single oral doses of VNT-101 (100-1500 mg) or placebo under fasting or fed (S5 only) conditions. Part 2 Multiple Ascending Dose (MAD) will enroll 30 participants into three cohorts (M1-M3) to receive multiple oral doses of VNT-101 (250-750 mg BID Days 1-5, QD Day 6) or placebo under fasting conditions. Dose escalation in both parts will proceed after Protocol Safety Review Team (PSRT) review. The primary objective for Part 1 is to evaluate the safety and tolerability of single ascending oral (SAD) doses of VNT-101 in healthy adult participants under either fasting or fed conditions. The primary objective for part 2 is to evaluate the safety and tolerability of multiple ascending oral (MAD) doses of VNT-101 in healthy adult participants.

The goal of this InTroDuce-Programme interventional trial aims to test whether a web-based educational program can improve pregnant women's knowledge about Influenza and Tdap vaccinations and increase their intention to get vaccinated in the future. The main questions it aims to answer are: Does the InTroDuce-Programme increase knowledge and future intention of pregnant mothers to get vaccinated against Influenza and Tdap? How does demographic factors, attitudes and barriers affect vaccination decisions among pregnant mothers? Researchers will compare InTroDuce-Programme to standard care (routine antenatal care) to see if InTroDuce-Programme works to improve knowledge and future intention of pregnant mothers to be vaccinated against Influenza and Tdap. Participants will: Receive the web-based educational module (InTroDuce-Programme), which covers the importance, safety, and effectiveness of vaccinations, as well as addressing common concerns. Be followed up one month after the intervention. Answer questionnaires before and after the intervention to measure changes in vaccination knowledge and future intention to get vaccinated

This study consists of two parts: Part A Surveillance and Part B Transmission. The main purpose of Part A is to evaluate the prevalence of pre-dose and treatment-emergent amino acid substitutions in pediatric participants' \<12 years with influenza treated with baloxavir marboxil. Part B will include a subset of Part A participants who have household contacts (HHCs) recruited to the study. Part B will evaluate the incidence of onward influenza transmission from pediatric index participants (IPs) under 5 years of age and those aged 5 to under 12 years, treated with baloxavir marboxil, to their HHCs. Participants will no longer be enrolled to Part B Transmission as per protocol version 3.

This study will investigate the effects of woodsmoke (WS) exposure on human nasal mucosal immune responses to viral infection. The study tests the hypotheses that WS exposure modifies biomarkers of nasal mucosal immune function, increases in Live Attenuated Influenza Virus (LAIV) -induced nasal symptoms, and reduces mucosal antibody production.

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-55 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza A (H3N2) viral challenge.

The purpose of this study is to determine whether drinking pasteurized milk (milk heated to kill harmful germs) that contains inactive particles of a flu virus called A(H5) could lead to the detection of the virus in the nose or throat. Inactive particles are not capable of causing disease. The results will help the Centers for Disease Control and Prevention (CDC) better understand how milk consumption could affect flu surveillance. Investigators also want to see if the body produces antibodies in response to this milk consumption.

This trial will use a previously validated platform, to quantitatively assess antiviral effects in low-risk patients with high viral burdens and uncomplicated influenza, to determine in-vivo antiviral activity. In this randomised, open-label, controlled, group sequential, adaptive, platform trial, we will compare the performance of available influenza antivirals, and those with potential activity, relative to the control (no treatment) and each other. AD ASTRA study is supported by the Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator

This study plans to learn more about whether a stakeholder-informed, standardized inpatient vaccination program will increase influenza vaccination rates of hospitalized children across US pediatric health systems. The first part of the study is to form a multidisciplinary team of stakeholders, including parents, providers, nurses, pharmacists, informaticists, data analysts and communication experts across three sites in synthesizing a best practice implementation guide for an inpatient influenza vaccination program, which will then be piloted at these three sites.