The aim of the study is to investigate the safety and immunogenicity of the RSV/Flu-01E vaccine for the prevention of respiratory syncytial virus infection in volunteers aged18 to 59 years and over 60 years.
Study includes 60 participants in three cohorts. First cohort includes 15 volunteers aged 18 to 59, randomized at 2:1 ratio, to receive low dose RSV/Flu-01E vaccine or placebo, correspondingly. Second cohort includes 15 volunteers aged 18 to 59, randomized at 2:1 ratio, to receive high dose RSV/Flu-01E vaccine or placebo, correspondingly. Third cohort includes 30 participants aged 60 years and older, randomized at 2:1 ratio to receive high dose RSV/Flu-01E vaccine or placebo. Duration of the study for each participant is about 6 months (no more than 190 days).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
60
Participants will receive single intranasal injection of A/H1N1pdm09 recombinant attenuated influenza vector (7.7 lg EID50) with modified NS gene coding for the F antigen of respiratory syncytial virus
Participants will receive single intranasal injection of A/H1N1pdm09 recombinant attenuated influenza vector (8.4 lg EID50) with modified NS gene coding for the F antigen of respiratory syncytial virus
Participants will receive single intranasal injection of Placebo
Smorodintsev Research Institute of Influenza
Saint Petersburg, Russia
Number of participants with local and systemic adverse events (AEs) and serious adverse events (SAEs)
* 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. * Evaluation of influenza A virus shedding evaluated by immunochromatographic rapid test in nasal swab samples in control points after vaccination
Time frame: Throughout the study, average of 6 months
Level of RSV F antigen-specific cytokine producing T-cells
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 ICS/ELISPOT
Time frame: Days 1, 7, 28, 90, 180
Level of RSV F antigen-specific cytokine release in whole blood assay
Change from baseline in the cytokine concentration in whole-blood cytokine release assay upon in vitro stimulation with RSV F-peptide epitopes measured in ELISA
Time frame: Days 1, 7, 28
Level of RSV F antigen-specific mucosal IgA antibody in saliva/nasal secrets
Change from baseline in the level of secretory IgA antibody specific to RSV F-antigen measured in ELISA in nasal secret/saliva
Time frame: Days 1, 28
Level of RSV F antigen-specific IgG antibody
Changes in the levels of RSV F antigen-specific total serum IgG antibodies measured in ELISA in serum
Time frame: Days 1, 28, 90, 180
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Proportion of responders to vaccination
Proportion of participants who responded to vaccination by significant increase in any of the immunogenicity parameters at any of the time points. The increase is considered significant if the fold change of the parameter value exceeds the conventional threshold, measured as geometric mean fold change in Placebo group multiplied by two geometric mean standard deviations.
Time frame: Days 7, 28
Concentration of cytokines in nasal secrets after vaccination
Change from baseline in the concentration of cytokines in nasal secrets measured in ELISA (pg/ml, 13-plex assay, IFN-α2, TSLP, IL-1α, IL-1β, GM-CSF, IL-11, IL-12p40, IL-12p70, IL-15, IL-18, IL-23, IL-27, IL-33)
Time frame: Days 1, 2, 3
Influenza specific systemic antibody immune response
Change from baseline in the titer of influenza specific antibodies in serum measured in hemagglutination inhibition/microneutralization assay
Time frame: Days 1, 28
Influenza specific local antibody immune response
Change from baseline in the level of influenza specific IgA antibodies in nasal secret/saliva measured in ELISA
Time frame: Days 1, 28