Pertussis (Whooping Cough)

This is a phase IV, open-label, non-randomized study to demonstrate superior immunogenicity and safety of a second booster dose of Pertagen® as compared to Adacel® at 10 years after the first booster vaccination and to evaluate the long-term persistence of specific antibodies induced by BioNet's recombinant aP (Pertagen®) and TdaP (Boostagen®) vaccines and a chemically-detoxified Tdap vaccine (Adacel®) at 10 years after the first booster in participants who were vaccinated in the phase II/III trial (Protocol No. TDA202) conducted from July 2015 to November 2016. Only those who were enrolled in the initial TDA202 study and had completed TDA202 1-year follow-up will be recruited for this 10-year follow-up study. Participants from all 3 vaccine groups (i.e., participants who had received a single dose of one of the 3 study vaccines (Boostagen®, Pertagen®, or Adacel®) and completed 1-year follow-up visit at Day 336±28 days during the TDA202 study will be called in for informed consent process at Visit 0 (Screening) at approximately 10 years (range, 9.5-10 years) following vaccination. At Visit 0, Screening visit, participants who have signed the written Informed Consent Forms will be screened for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination) and those who fulfill the pre-defined inclusion criteria without meeting any exclusion criteria will be enrolled into the study. The screening visit and Visit 1 (Day 0) can be completed on the same day. Once enrolled, a blood sample (approx. 5 mL) will be taken from all participants at Visit 1 (before second booster vaccination) and at Visit 2 (28 days after second booster vaccination) as shown in the diagram below (Figure 1). At Visit 1, Day 0 (enrollment and second booster vaccination), a blood sample (approx. 5 mL) will be taken from all enrolled participants. After blood collection, the participants who received Pertagen® and Boostagen® in the initial TDA202 study will be administered a single intramuscular injection of a second booster dose of Pertagen®. The participants who have received Adacel® in the initial TDA202 study will be given a single intramuscular injection of a second booster dose of Adacel® (Table 1). Composition of booster vaccines are presented in Table 2. The vaccine preparation and administration will be performed by appropriately trained study team and study nurses, respectively, who are delegated by the Principal Investigator. If a participant does not complete screening visit and Visit 1 (Day 0) on the same day, the screening process for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination), urine pregnancy test for female participants with childbearing potential and inclusion and exclusion criteria will be assessed again at Visit 1. Brief description of the study design for TDA202 10-year follow-up study: This is a phase IV, open-label, non-randomized study to demonstrate superior immunogenicity and safety of a second booster dose of Pertagen® as compared to Adacel® at 10 years after the first booster vaccination and to evaluate the long-term persistence of specific antibodies induced by BioNet's recombinant aP (Pertagen®) and TdaP (Boostagen®) vaccines and a chemically-detoxified Tdap vaccine (Adacel®) at 10 years after the first booster in participants who were vaccinated in the phase II/III trial (Protocol No. TDA202) conducted from July 2015 to November 2016. Only those who were enrolled in the initial TDA202 study and had completed TDA202 1-year follow-up will be recruited for this 10-year follow-up study. Participants from all 3 vaccine groups (i.e., participants who had received a single dose of one of the 3 study vaccines (Boostagen®, Pertagen®, or Adacel®) and completed 1-year follow-up visit at Day 336±28 days during the TDA202 study will be called in for informed consent process at Visit 0 (Screening) at approximately 10 years (range, 9.5-10 years) following vaccination. At Visit 0, Screening visit, participants who have signed the written Informed Consent Forms will be screened for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination) and those who fulfill the pre-defined inclusion criteria without meeting any exclusion criteria will be enrolled into the study. The screening visit and Visit 1 (Day 0) can be completed on the same day. Once enrolled, a blood sample (approx. 5 mL) will be taken from all participants at Visit 1 (before second booster vaccination) and at Visit 2 (28 days after second booster vaccination) as shown in the diagram below (Figure 1). At Visit 1, Day 0 (enrollment and second booster vaccination), a blood sample (approx. 5 mL) will be taken from all enrolled participants. After blood collection, the participants who received Pertagen® and Boostagen® in the initial TDA202 study will be administered a single intramuscular injection of a second booster dose of Pertagen®. The participants who have received Adacel® in the initial TDA202 study will be given a single intramuscular injection of a second booster dose of Adacel® (Table 1). Composition of booster vaccines are presented in Table 2. The vaccine preparation and administration will be performed by appropriately trained study team and study nurses, respectively, who are delegated by the Principal Investigator. If a participant does not complete screening visit and Visit 1 (Day 0) on the same day, the screening process for general health status (medical history, medication history, immunization history, history of receiving blood, blood component, immunoglobulin, immunosuppressive drugs or systemic corticosteroid, vital signs and physical examination), urine pregnancy test for female participants with childbearing potential and inclusion and exclusion criteria will be assessed again at Visit 1. Table 1: Vaccine groups and booster dose vaccination Vaccine group in Initial TDA202 study Second booster vaccination at Day 0 Total number of participants (N) per vaccine group Pertagen® and Boostagen® Pertagen® 84 Adacel® Adacel® 42 After the second booster vaccination, participants will be observed at the study site for at least 30 minutes to monitor for any immediate post-immunization reactions. Safety and reactogenicity in the participants will be assessed until end of study. The diary cards will be distributed to the participants to record post-immunization solicited local and systemic adverse events (AEs) until Day 7 and unsolicited AEs, serious adverse events (SAEs), and concomitant medications until Day 28 following vaccination. The study staff will contact the participants by phone on Day 7 (+4 days) to enquire on health status and to remind them to record any solicited local and systemic AEs, unsolicited AE, SAE and concomitant medications in the diary card. At Visit 2, Day 28 (+7 days), participants will return to the study site for blood sample collection (approx. 5 mL), reconciliation of information in the diary card, and any reported AEs, SAEs and concomitant medications. Safety and reactogenicity will be assessed until end of study. Solicited local and systemic AEs will be collected until Day 7 after the second booster vaccination. Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) will be collected until Visit 2 (Day 28) after the second booster vaccination. Visit 2 is considered the end of study. Blood samples collected from all participants at Day 0 (Visit 1) and Day 28 (Visit 2) will be processed for serum preparation. Serum samples will be stored at the laboratory at the study site and will be further shipped to BioNet-Asia Human Serology Laboratory where immunogenicity testing will be performed. At Day 0 (Visit 1) and Day 28 (Visit 2), ELISA testing to detect antibodies against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and PT neutralizing assay in Chinese Hamster Ovary (CHO) cells will be performed for all enrolled participants. At Day 0 (Visit 1), ELISA testing to detect antibodies against tetanus toxoid (TT) and diphtheria toxoid (DT) will be performed for participants who received Boostagen® and Adacel® in TDA202 initial study. Data management and statistical analysis will be performed by the Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Bangkok, Thailand.

The goal of this clinical trial is to investigate the effect of booster vaccination with acellular pertussis vaccine on colonization with Bordetella pertussis using a controlled human infection model in healthy volunteers. The main questions it aims to answer are: * Whether booster vaccination with Tdap-IPV reduces Bp colonisation after intranasal challenge with the standard Bp inoculum dose compared to the Td-IPV control group * Compare Bp colonisatation in participants vaccinated with Tdap-IPV after intranasal challenge with the standard and a 'high' Bp inoculum dose Research will compare Tdap-IPV vaccination - standard inoculum dose with Td-IPV vaccination - standard inoculum dose, and Tdap-IPV vaccination - standard inoculum dose with Tdap-IPV vaccination - high inoculum dose to see how Tdap-IPV vaccination and the high inoculum dose have an effect on colonisation rate. Participants will be vaccinated with Tdap-IPV or Td-IPV and 2-4 months later challenged with the standard or 'high' inoculum. After challenge there is a follow up visit for 28 days in which they fill in a daily symptom diary and have 6 visits to the hospital.

Stage 1 (Phase 2) 1\. To compare the immunogenicity and safety of LBVD to the licensed Control vaccines at 4 weeks after a three-dose primary series of vaccination given at 6-, 10- and 14-week of age Stage 2 (Phase 3) 1. To demonstrate the non-inferior immunogenicity of LBVD to the licensed Control Vaccine at 4 weeks after a three-dose primary series of vaccination given at 6-, 10- and 14-week of age 2. To demonstrate lot-to-lot consistency in the immunogenicity of three separate lots of LBVD at 4 weeks after a three-dose primary series of vaccination given at 6-, 10- and 14-week of age

Participants will receive Adebrelimab intravenously in combination with carboplatin /Cisplatin and etoposide during the induction phase (2 Cycles ). Thereafter, participants will receive concurrent chemoradiotherapy(thoracic radiation therapy and SBRT for metastases,combination with carboplatin /Cisplatin and etoposide for 1-2 Cycles).Then participants will receive Adebrelimab combination with carboplatin /Cisplatin and etoposide for 1-2 Cycles,followed by Adebrelimab maintenance until persistent radiographic PD, intolerable toxicity or withdrawal of consent during the maintenance phase.

In this study: 1. The participation is voluntary. 2. Before the trial, participants will receive some tests for screening. If qualified, investigators will officially invite them to join this trial. 3. The trial vaccine is LZ901 (100μg/0.5 mL). The placebo, which is aluminum hydroxide adjuvant, has no active drug. Participants will receive one of two as above mentioned. 4. This trial included a protective efficacy test and a batch-to-batch consistency test (immunization subgroup). Approximately 26000 subjects aged 40 years and older will be enrolled. Subjects will be randomized to receive either LZ901 or placebo in which about 3000 subjects will be enrolled into immunization subgroup and randomly receive three different batches LZ901 and one batch placebo at a ratio of 1:1:1:3. The immunization subgroup was designed to evaluate the batch-batch immunogenicity consistency among three different batches of LZ901, as well as the immunogenicity and immunogenicity persistence of the LZ901 at 12, 24, and 36 months after full immunization. 5. All subjects will receive the LZ901 or Placebo on day 0 and day 29. Subject will have 16 visits, including 5 on-site visits and 11 in-person visits except for subjects in the immunization subgroup who have 24 visits, including 8 on-site visits and 16 in-line visits. 6. The primary objective was to evaluate the Vaccine Efficacy (VE) of LZ901 against herpes zoster, as compared with placebo, after 30 days of full immunization in people 40 years of age and older. 7. The secondary objective was to evaluate the protective efficacy of LZ901, as compared with placebo, against laboratory-confirmed cases of HZ after 30 days of full vaccination in people 40 years of age and older. To evaluate the safety of LZ901. The immunogenicity of LZ901was evaluated (immunization subgroup). To evaluate the batch-to-batch consistency of immunogenicity of three batches of LZ901 in subject aged ≥40 years (immunization subgroup). 8. An exploratory objective was to evaluate the effect of LZ901 on reducing the severity of PHN in HZ subjects ≥40 years old." To evaluate the efficacy of LZ901 compared with placebo in preventing PHN in subjects ≥40 years old with HZ efficacy endpoint. The immunogenicity of LZ901 was evaluated at 12, 24 and 36 months after full immunization in subject ≥40 years old (immunization subgroup).

Respiratory signs and symptoms consisting of wheeze, cough, and breathlessness are obtained in a manual fashion through history taking and physical examination by the healthcare professional. Auscultation of the lung assesses airflow through the trachea-bronchial tree and is helpful in diagnosing various respiratory disorders. AeviceMD is a wearable device that can acquire and process lung sounds, thus assisting in the detection of abnormal lung sounds. The primary objective of this study is to determine if AeviceMD can detect wheeze of pediatrics and adults as accurately as a physician through auscultation. The secondary objective is to investigate if AeviceMD can be used for remote auscultation of breath sounds.

Viral respiratory tract infections are very common in children. They contribute to missed time in school, work disruption for caregivers and can also cause severe illness requiring hospitalization and rarely death. In the 2022-2023, influenza, RSV and SARS-CoV-2 viruses infected a large number of children which strained the pediatric healthcare system in many jurisdictions. Unfortunately, there continues to be limited data on duration of infectiousness and transmission risk of these viruses to inform public health decisions during times when there is significant circulation of these viruses.

This is an observer-blind, randomized, active-controlled, multi-centric study in healthy infants and toddlers to assess the immunogenicity and safety of SIIPL reduced IPV hexavalent vaccine in comparison with the licensed SIIPL HEXASIIL® vaccine. One thousand five hundred and fifty-seven infants aged 6-8 weeks (42 to 56 days, both days inclusive) will be randomized in a 2:1 ratio (1038 infants in SIIPL reduced IPV hexavalent group and 519 in SIIPL HEXASIIL® group), to receive a 3-dose primary vaccination series followed by their booster doses, respectively. The safety and immunogenicity data collected up to 28 days following third vaccination i.e., Visit 7, shall be submitted to the regulatory authority. All subjects will be followed up further for booster dose. After Visit 7 (i.e., 28 days following completion of primary vaccination series) subjects will be followed up for safety every 3 months starting from the age of 6 months (i.e., at 6, 9, 12, 15, 18, and 21 months of age) until they receive the booster dose anytime between 12-24 months. There will be post booster follow up visit (EOS visit) 28 days after the booster immunization i.e., Visit 10 to assess the safety and post booster immunogenicity.

The clinical significance of pulmonary embolism (PE) limited to the subsegmental pulmonary arteries, so called isolated subsegmental pulmonary embolism (SSPE), remains controversial. Whether isolated SSPE represents "true" PE, a clinically more benign form of PE, a physiologic lung clearing process, or a false positive result (artifact) is currently unclear and hence, whether patients with isolated SSPE benefit from anticoagulant treatment is uncertain. Despite growing evidence from observational studies that withholding anticoagulation may be a safe option in selected patients with isolated SSPE (i.e., those without concomitant deep vein thrombosis, cancer, etc.), most patients with isolated SSPE receive anticoagulant treatment, which is associated with an increased risk of bleeding. The overall objective of the randomized controlled SAFE-SSPE trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation compared to anticoagulation treatment in low-risk patients with isolated SSPE.

This research protocol involves one or more of the following procedures in healthy volunteers and patients with known or suspected predisposition to respiratory infection who are enrolled in National Institutes of Health (NIH) protocols: 1) Adults only: bronchoscopy with sampling of bronchoalveolar lavage fluid and epithelial cells in healthy adult volunteers and patients; 2) Adults and Children: sputum induction for collection of sputum specimens; 3) Adults and Children: nasal mucosal biopsies and brushings for sampling of epithelial cells; 4) Adults and Children: measurement of nasal nitric oxide production; 5) Adults and children: collection of exhaled breath condensate; 6) Adults and children: measurement of nasal potential difference; 7) Adults and children: exhaled aerosol mask sample collection; Adults and children: 8) cough aerosol collection. The cellular and acellular samples will be separated, and stored or transferred to the appropriate laboratories investigating these diseases. Alveolar macrophages are the predominant (\>95%) cell type present in the lavage of normal subjects. Alveolar macrophages play a central role in the initiation and propagation of lung inflammation by releasing cytokines (i.e., interleukin-1, tumor necrosis factor) and chemokines (i.e., interleukin-8, monocyte chemotactic protein, macrophage inflammatory protein) that activate other resident cells and recruit inflammatory cells to a local nidus of inflammation. Airway epithelial cells are known to release a variety of mediators as well. Thus, the interaction of cells with mediators generated by alveolar cells and bronchial epithelial cells during acute inflammation is a key element in the initiation of pulmonary inflammatory responses. Bronchoalveolar lavage (BAL), bronchial brushings, and mucosal biopsies are standard diagnostic techniques done through the bronchoscope to obtain samples of alveolar and bronchial specimens for diagnosis of infection, malignancy, or non-infectious inflammation. Nasal mucosal scrape biopsy is a minimally invasive method of obtaining airway epithelial cells to diagnose disorders of airway clearance associated with abnormal cilia (hair-like structures on airway lining cells). Sputum induction is a routinely performed procedure to facilitate the collection of respiratory secretions (mucus) through stimulation of cough with inhalation of an aerosolized concentrated salt-water solution. Exhaled breath condensate is simply collected by breathing normally through a plastic tube inserted into a chilled cylinder. Nasal potential difference is performed by placing a small needle under the skin of the forearm that is connected to a salt solution bridge and resting a small catheter on the surface of the nose through which various salt solutions are dripped. The objective of this protocol is to analyze bronchoalveolar lavage fluid, airway epithelial cells, sputum, and exhaled breath specimens and bedside physiologic measurements from healthy volunteers and from patients who acquire respiratory infections to look for differences in immune function and to discover new pathways of infectious disease susceptibility. We hypothesize that studying cellular responses to infection and inflammatory markers released from these cells will further our understanding of human susceptibility to respiratory tract infections. Five hundred fifty subjects (250 healthy volunteers and 300 patients) will undergo one or more of the following: 1) bronchoscopy with bronchoalveolar lavage, bronchial brushings, endobronchial biopsies; 2) nasal mucosal scrape and/or brush biopsies; 3) sputum induction 4) exhaled breath condensate to obtain specimens for in vitro investigations and comparisons of both the cellular and acellular components. Bedside measurements 5) nasal nitric oxide production and 6) nasal potential difference 7) exhaled aerosol mask sample collection 8) cough aerosol collection 9) Exhaled particle collection; 10) Lung Clearance Index (LCI) may be done to assess airway infection and epithelial cell functions in real-time.