Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory Syncytial Virus, RSV, Vaccine
Brief summary
In this study we are testing a new vaccine against Respiratory Syncytial Virus (RSV). This virus can cause respiratory infections such as bronchiolitis and pneumonia. It affects all ages, but especially infants, adults with a suppressed immune system, and the elderly. RSV only infects humans and occurs in epidemics each winter. It is the single most common cause of severe respiratory illness in children. There is no effective anti-viral medication to treat RSV infections. There is a monoclonal antibody, which can be given to 'at-risk' children given by injection on a monthly basis during winter to provide short term protection against infection, but it is only partially effective and prohibitively expensive. Currently, there is no licensed vaccine to prevent RSV infection and there remains a real need to develop a vaccine as a cost-effective method to save lives and reduce the cost of disease caused by RSV.
Detailed description
We are testing two new RSV vaccines, given in different combinations and by different routes of administration. Each vaccine uses the same RSV proteins to stimulate immune responses. These proteins are the F (Fusion), N (Nucleocapsid) and M2-1 (Matrix) proteins. The F protein sits on the surface of the virus and is needed to infect human cells. Antibodies to this protein are an important mechanism to prevent infection. The N and M2-1 proteins are needed for viral replication and are targets of immune recognition. The two vaccines in this study contain all three of these proteins. However, they are delivered into the body using different 'vectors', which are harmless carrier viruses. In this study, we have employed two different vectors:a simian adenoviruses (PanAd3) and Modified Vaccinia virus Ankara (MVA). We administer these vaccines using a 'prime-boost' strategy, in which one of these vaccines is used to 'prime' the immune system, which is then 'boosted' 4 or 8 weeks later, depending on the groups, by administration of an alternative vaccine or the same vaccine given by a different route.
Interventions
BIOLOGICALPanAd3-RSV given intra-nasally (high dose)
High dose = 5x10\^10 vp
BIOLOGICALMVA-RSV given by intra-muscular injection (high dose)
High dose = 1x10\^8 pfu
BIOLOGICALPanAd3-RSV given by intra-muscular injection (high dose)
High dose = 5x10\^10 vp
BIOLOGICALPanAd3-RSV given intranasally (low dose)
Low dose = 5x10\^9 vp
BIOLOGICALMVA-RSV given by intra-muscular injection (low dose)
Low dose = 1x10\^7 pfu
BIOLOGICALPanAd3-RSV given by intra-muscular injection (low dose)
Low dose = 5x10\^9 vp
Sponsors
ReiThera Srl
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Participants must satisfy all of the following criteria to be considered eligible for the study: * Willing and able to give informed consent for participation in the study * Aged between 18 and 50 years (Groups 1-4) or aged 60-75 years (Groups 5-9) * In good health as determined by * Medical history * Physical examination * Clinical judgment of the investigators * Willing to use effective contraception * Females: The oral contraceptive pill, contraceptive implant or barrier methods from one month prior and for the duration of the study (Groups 1-4 only) * Males: Barrier contraception from V1 until 3 months after the last vaccination * Able to attend the scheduled visits and to comply with all study procedures * Willing to allow his or her General Practitioner and/or Consultant, if appropriate, to be notified of participation in the study * Confirmation from GP that they are aware of the inclusion and
Exclusion criteria
and are satisfied from their knowledge of the volunteer that they are suitable to enroll * Willing to provide their National Insurance/Passport number for the purpose of TOPS registration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety | 52 Weeks | The recording and assessment of local and systemic adverse events following administration of each vaccine dose; * Fever * Headache * Nausea and/or vomiting * Malaise * Myalgia * Arthralgia * Injection site adverse events (for IM administered vaccine); pain or tenderness, induration, redness and swelling * Nasal site adverse events (for IN administered vaccine); pain or tenderness, irritation and discharge * Blood parameters * Any unsolicited symptom(s) not listed above |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | 52 weeks | Immunological assays to study immune responses to each vaccine, including: * Serum antibody response to RSV F antigen * Serum antibody response capable of RSV neutralization * Quantification of circulating vaccine-induced B-cell secreting antibodies (IgA and IgG) against RSV F antigen * Quantification of circulating vaccine-induced T-cell responses against RSV antigens F, N and M2-1 * Any further exploratory immunology to detect vaccine related immune responses |
Countries
United Kingdom
Outcome results
None listed