Respiratory Synctial Virus Infections
Conditions
Keywords
Respiratory syncytial virus infection, Mucosal Vaccine, Influenza Vector, Intranasal Immunization
Brief summary
The aim of the study is to investigate immunogenicity and safety of the RSV/Flu-01E intranasal vaccine for the prevention of respiratory syncytial virus infection in volunteers over 60 years
Detailed description
Study includes 120 participants over 60 years randomized at 3:1 ratio, to receive single intranasal dose of RSV/Flu-01E vaccine or placebo, correspondingly. Duration of the study for each participant is about 4 months (118±3 days)
Interventions
BIOLOGICALRSV/Flu-01E
Participants will receive single intranasal injection of RSV/Flu-01E vaccine in 0.5 ml, containing 8.4 lg EID50 of A/H1N1pdm09 recombinant attenuated influenza vector with modified NS gene, encoding for the F antigen of respiratory syncytial virus
OTHERPlacebo
Participants will receive single intranasal injection of physiological buffer solution in 0.5 ml
Sponsors
Pavlov First Saint Petersburg State Medical University
St. Petersburg City Polyclinic No. 34
Research Institute of Influenza, Russia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Availability of signed informed consent 2. Adult men and women over the age of 60. 3. The diagnosis is healthy, verified according to standard clinical, laboratory and instrumental methods of examination or the presence of a chronic disease, if the researcher considers it to be compensated. 4. BMI from 18 to 30 kg/m2. 5. The ability and willingness to make entries in the diary of self-observation, as well as to carry out all the visits foreseen in the study for control medical observation 6. Negative test for alcohol in exhaled air 7. Values of the complete blood count and biochemical blood analysis (during the screening) within 0.9\*reference range lower limit and 1,1 \* reference range upper limit 8. Negative tests for HIV, hepatitis B, hepatitis C, and syphilis
Exclusion criteria
1. Participation in another clinical study within three months prior to the start of the current study; planning to participate in another study during the current study period 2. Contact with COVID-19 patients within 14 days prior to the start of the clinical study 3. Positive rapid test result for SARS-CoV-2 antigen 4. Immunization with any other non-study vaccine product within three weeks prior to enrollment in the current study, or refusal to postpone such until the end of the three-week period after completion of the current study 5. Regular use of nasal irrigation therapy during the last six months prior to enrollment in the current study or episodic use of the above method of treatment in the two weeks prior to the screening 6. History of frequent nosebleeds (\>5) during the year prior to the current study 7. Features of the nasal anatomy that may complicate intranasal administration of the study drug 8. Surgical interventions or traumatic injuries in the sinus area, paranasal sinuses, or traumatic injuries of the nose within a month before screening 9. Symptoms of acute respiratory disease, including fever, or other acute illness at the time of screening or within two weeks prior to screening 10. Treatment with immunoglobulins or other blood derived medications in the three months prior to screening or planning such treatment during the period of participation in the current study 11. Donation of blood/plasma (450 ml or more) less than 2 months prior to screening. 12. The presence or suspicion of the presence of various immunosuppressive or immunodeficiency conditions or continuous use (the drug was prescribed for more than 14 days without a break) of immunosuppressive drugs, immunomodulators for 6 months before the screening. 13. History of bronchial asthma 14. Hypersensitivity and the presence of severe allergic reactions, including Quincke's edema, anaphylactic shock after the previous administration of any vaccine 15. History of wheezing after previous immunization with live influenza vaccine 16. Other adverse events after immunization (fever above 40°C, syncope, non-febrile convulsions, anaphylaxis) when there is a minimal likelihood that they are associated with a previous administration of any vaccine 17. Suspicion of hypersensitivity to any component of the study vaccine, including egg protein 18. Acute or chronic clinically significant lung, cardiovascular, hepatic, endocrine, neurological, or psychiatric disorders, or impaired renal function identified by history, physical examination, or clinical laboratory findings that, in the opinion of the investigator, may influence the outcome of the study 19. History of oncological diseases 20. History of thrombocytopenic purpura or bleeding disorders 21. History of convulsions 22. Tuberculosis or residual changes after tuberculosis according to the anamnesis and / or available medical documentation 23. Chronic alcohol dependence or chronic use of illicit drugs, drug abuse 24. Claustrophobia and social phobia according to history and / or available medical records 25. Inability to read Russian; inability or unwillingness to understand the essence of the study 26. Military personnel serving in the military or law enforcement officers. 27. Special diet (eg, vegetarian, vegan, salt-restricted) or lifestyle (night work, extreme physical activity) 28. Any condition that, in the opinion of the investigator, may increase the risk to the health of a volunteer participating in the study or affect the results of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of RSV F antigen-specific cytokine producing CD4+ and CD8+ T-cells | Days 1, 7, 28 | Change from baseline in the level of cytokine producing CD4+ and CD8+ T-cells upon in vitro stimulation of PBMC with RSV F-peptide epitopes measured by FACS/ELISPOT |
| Level of the RSV F antigen-specific Th1/Th2 cytokine release in whole blood assay | Days 1, 7, 28 | Change from the baseline of the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with RSV F-peptide epitopes measured in ELISA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of RSV F antigen-specific IgG antibody in serum | Days 1, 28, 118±3 | Change from the baseline in the level of RSV F antigen-specific serum IgG antibodies measured in ELISA |
| Influenza specific systemic antibody immune response | Days 1, 28, 118±3 | Change from the baseline in the titer of influenza specific antibodies in serum measured in hemagglutination inhibition/microneutralization assay |
| Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs) | Throughout the study, average 4 months | Adverse events (AEs) and serious AEs (SAEs), both vaccine related, and non-vaccine related; AEs/SAEs of particular importance: * Immediate AEs (allergic reactions) occurring within two hours of vaccination. * Post-vaccination reactions (anticipated clinical manifestations of a local and systemic nature), usually due to intranasal vaccination between two hours and the next 7 days after vaccination |
| Level of influenza specific cytokine release in whole blood assay | Days 1, 7, 28 | Change from the baseline of the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with influenza A/H1N1pdm antigen measured in ELISA |
| Level of B-cell populations | Days 1, 7, 28 | Change from the baseline in the relative amount of B-cell populations in PBMC measured by FACS |
| Level of mucosal IgA antibody in nasal secret | Days 1, 28 | Change from the baseline in the level of IgA antibody measured in ELISA in nasal secret |
| Concentration of cytokines in nasal secrets after vaccination | Days 1, 2, 3 | Change from baseline in the concentration of cytokines in nasal secrets measured in ELISA |
Countries
Russia
Outcome results
None listed