Clinical Research Directory

Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates

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.

Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)

Background: Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should. Objective: To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time. Eligibility: People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed. Design: Participants will have 5 study visits over 1 year. They will have various tests and procedures: Smell tests. They will have several tests that involve smelling different items and answering questions. Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits. Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner. Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap. Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose. Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages. Samples of blood, urine, and nasal fluid will be taken.

H1ssF Flu Vaccine Clinical Trial

This is a two-arm, open-label, randomized, phase 1, controlled clinical trial intended to evaluate the safety and immunologic response to the experimental vaccine H1ssF (H1 stabilized stem ferritin nanoparticle) and the seasonal flu vaccine Flucelvax.

Screening for LID Clinical Studies Unit Healthy Volunteer Protocols

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.

BPL-1357 Against H1N1 Influenza Virus Challenge

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. ...

Effectiveness of An Influenza/COVID-19 Vaccine (mCombriax [mRNA-1083]) in Adults ≥ 65 Years

The purpose of this pragmatic randomized trials is to evaluate the comparative vaccine effectiveness (cVE) of mCombriax® (mRNA-1083) versus same day co-administration of the active comparators (i.e., high-dose influenza vaccine/Efluelda® and mRNA-1273/Spikevax®) among adults aged 65 years and older.

Cellular and Molecular Characterization of the Immune Response in Healthy NIH Employees atBaseline, and After Immunization With the H1N1 or Seasonal Influenza Vaccines

Background: \- Seasonal influenza is a major health problem whose impact is typically reduced by vaccination. The H1N1 (swine flu) influenza virus is an emerging pathogen that has the potential to cause devastating illness and even death in the coming months. Currently, there are limited data on the cellular and molecular immune responses in adult recipients of either the seasonal or the H1N1 influenza vaccines. Objectives: \- To obtain blood and nasal wash samples and perform laboratory studies to characterize the immune response in healthy adult volunteers at baseline and after immunization with the seasonal or H1N1 influenza vaccines. Eligibility: \- Adult employees at least 18 years of age of the NIH Clinical Center who are deemed healthy by a brief medical history and physical examination and routine blood testing. Design: * Before the start of the influenza season, volunteers will receive either the seasonal influenza vaccine or the H1N1 vaccine when it becomes available. If the H1N1 vaccine is available at the start of the season, volunteers will receive both the seasonal vaccine and the H1N1 vaccine. * Blood will be drawn over an 8-week period. Volunteers must not eat anything for 8 hours prior to the blood draw. The sequence of the blood draws is as follows: 2 weeks before vaccination; right before vaccination; and 1, 7, 14, 28, and 60 days after vaccination. * Two to four nasal washings will be collected by a nurse before volunteers receive the vaccination(s) and 28 days after the vaccination. * Prevaccine and postvaccine blood and nasal wash samples will be compared to determine volunteers immune responses. * Research samples will be stored indefinitely and will be used strictly for laboratory experiments.

Dime La VerDAD: Verify, Debunk, and Disseminate

Dime la Verdad (Tell me the truth) will evaluate the use of storytelling by community health workers as a communication strategy to disseminate reliable health information on social media and encourage informed decision-making in favor of recommended immunizations in communities with high morbidity and mortality due to respiratory virus infections. Dime La Verdad is an innovative social media capacity-building program based on theoretical frameworks related to health communication that empowers community health workers to disseminate reliable information about respiratory virus protection strategies through the use of personal narratives on social media. The proposed work will use a rigorous stepped wedge design to 1) deliver a scalable program of science communicators using an adapted curriculum grounded in principles of health communication, 2) evaluate how diffusion of health messaging is perceived on social media, and 3) discern how use of personal narratives to enhance science communication can encourage informed decision-making to promote evidence-based immunization practices and improve health outcomes.

Light-based Immunomodulation for Guarding Against Human Respiratory Tract Infections

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.

Smart Analysis and Decision-Making for Emerging Infectious Diseases

Emerging infectious diseases, such as COVID-19, mpox, and dengue fever, are characterized by rapid transmission, wide impact, and high uncertainty, posing ongoing threats to global public health. While China achieved significant success in COVID-19 control, the response also revealed key challenges, including fragmented information, delayed risk perception, experience-dependent assessment, and inefficiencies in complex decision-making. This study aims to establish a smart technology system covering the full chain of "risk perception-situational assessment-intelligent decision-making-comprehensive evaluation." Specific objectives include: Constructing a global disease burden database and knowledge graph for emerging infectious diseases; Developing early risk assessment models covering the full transmission spectrum (cross-species, imported, and local outbreak); Building an AI-driven collective intelligence decision-support tool for epidemic control; Developing precise intervention frameworks and comprehensive evaluation indicators for key populations (e.g., elderly, students); Integrating the above technologies into a multi-agent toolkit and evaluating its effectiveness through a cluster randomized controlled trial involving at least 36 district/county-level CDC clusters across five provinces/municipalities (Guangdong, Zhejiang, Hubei, Sichuan, and Shanghai). Three eligible CDC staff members will be enrolled from each participating cluster, including one CDC director or relevant leader responsible for infectious disease prevention and control and two professional staff members engaged in acute infectious disease surveillance, risk assessment, decision-making, or emergency response. Accordingly, at least 108 participants will be enrolled, and the final anticipated enrollment will be determined by the total number of participating clusters. The intervention group will use the smart toolkit alongside routine practices, while the control group will follow routine practices only. The primary outcome is response time for epidemic assessment and decision-making (hours from risk perception to decision completion). Secondary outcomes include epidemic control effectiveness, user satisfaction, and socioeconomic benefits. The intervention period is 3 months, starting around July 2026 and ending in December 2027. This study has been approved by the Peking University Biomedical Ethics Committee. The study does not involve individual patient data; all data are aggregated at the district/county level from CDC sources or publicly available data. Anonymous questionnaires do not collect any personal identifiable information.

Respiratory Virus Sampling and Repository

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.

Impact of High Dietary Fiber on Microbiome and Vaccine Responses

To learn if diet can enhance the microbes (such as bacteria and viruses) found in your gut and improve the body's immune response to the influenza (flu) vaccine.

Association Between Gut Microbiome and Dietary Determinants and Vaccine Response

This study evaluates the association between gut microbiome and dietary determinants and vaccine response. This study aims to learn if diet and the microbes (such as bacteria and viruses) found in your gut affect the body's immune response to the influenza vaccine.

A Study of mRNA-1018-H5 Pandemic Influenza Vaccine in Healthy Adults

The purpose of this study is to evaluate humoral immunogenicity after 2 doses of mRNA-1018-H5, and to evaluate the safety and reactogenicity of mRNA-1018-H5 in adults ≥18 years of age.

Fluad vs. Fluzone High-Dose Vaccine Effectiveness Among Adults ≥65 Years

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.

Surveillance, Assessment and Detection of Influenza Associated Respiratory Infections in HIV Positive and Negative Individual in Lusaka, Zambia.

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)

Phase 1/2 Study of a Plant-Based Seasonal Recombinant Trivalent VLP Influenza Vaccine

This Phase 1/2 study is intended to assess the safety, tolerability, and immunogenicity of recombinant TVLP in adults 18-64 and 65 years of age and above and to confirm the dose(s) to be developed further in these two age cohorts.

Virological Surveillance of Acute Respiratory Infection in Primary Health Care in Metropolitan France

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.

Phase I/II Clinical Trial of Influenza Vaccine (Split Virion), Inactivated (High Dose)

This is a randomized, double-blind, active-controlled Phase I clinical trial to evaluate the safety and immunogenicity of Influenza Vaccine (Split Virion), Inactivated (High Dose) developed by Sinovac.

Natural History of Systemic and Nasal Mucosal Immunity to Influenza and SARS-CoV-2 in Adults After Vaccination

Background: Influenza (flu) vaccinations are required for all NIH staff members who have direct contact with patients. COVID-19 vaccines are recommended for persons 6 months of age and older. Researchers want to learn about immunity in NIH staff members who get a flu and/or COVID-19 vaccine. Objective: To understand what happens to the body s immune system throughout the year after getting the flu and/or COVID-19 vaccine. Eligibility: Adults ages 18 and older who work at NIH and plan to get the current season s flu vaccine and/or COVID-19 vaccine. Design: Participants will not get any vaccines as part of this study. Participants will be screened with a medical history and medicine review. They will get a survey via email. It will ask about their flu and SARS-CoV-2 history and vaccinations. Participants will have 12 monthly visits at NIH. If during that year they get both flu and SARS-COV-2 vaccines, their participation will be extended. Once a month, participants will be contacted. They will discuss any new medicines, recent vaccinations, or changes in medical history. Once a month, participants will have blood drawn. Once a month, participants will have nasal sampling. A small, flat absorptive strip will be placed in the nostril to soak up mucus. Participants will press against the outside of their nostril with their finger for 1 minute. Participants may be able to collect samples at home and mail them to NIH if they are not able to visit in person. Participation will last for about 12 13 months.

Immunogenicity of Influenza Vaccinations

This study is a randomized immunogenicity study in an enrolled cohort with active surveillance for influenza-like illness (ILI). During this study, participants will be randomly assigned to receive an approved cell culture-based influenza vaccine (Flucelvax®) versus a licensed comparator influenza vaccine (Flublok®). Blood samples from participants will be collected for measurement of biomarkers of immune response at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Participants will be asked if they wish to also provide saliva specimens at baseline (visit 1; day 1), post-vaccination (visit 2; day 29), and post-season (visit 3; day 181). Serum and peripheral blood mononuclear cells (PBMC) and plasma samples will be isolated from whole blood and tested for biomarkers of vaccine immunogenicity, and duration of antibody responses. Participants will receive electronic surveys via email or text message weekly asking about changes in health status and new ILI symptoms; those reporting illness may be asked to provide a respiratory swab for laboratory testing for influenza and other respiratory viruses and up to 2 additional blood draws (acute \[\<10 days after symptom onset\] and convalescent \[28 days after acute visit if lab-confirmed positive for influenza\]).

Influenza Vaccination Strategy for Patients With Hematologic Malignancy

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

pH1N1 Blinded Challenge Study

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.

Baloxavir and Oseltamivir for the Treatment of Severe Influenza Infection in Immunocompromised Patients

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.