Safety and immunogenicity of novel respiratory syncytial virus (RSV) vaccines based on the RSV viral proteins F, N and M2-1 encoded by simian adenovirus (PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, dose-escalation, single-centre, phase 1 clinical trial in healthy adults.
BACKGROUND
Respiratory syncytial virus (RSV) infection causes respiratory disease throughout life, with infants and the elderly at risk of severe disease and death. RSV001 is a phase 1 (first-in-man), open-label, dose-escalation, clinical trial of novel genetic viral-vectored vaccine candidates PanAd3-RSV and modified vaccinia virus Ankara (MVA)-RSV. The objective of RSV001 is to characterise the (primary objective) safety and (secondary objective) immunogenicity of these vaccines in healthy younger and older adults.


METHODS
Heterologous and homologous 'prime'/boost combinations of PanAd3-RSV and single-dose MVA-RSV are evaluated in healthy adults. 40 healthy adults aged 18-50 years test one of four combinations of intramuscular (IM) or intranasal (IN) PanAd3-RSV prime and IM PanAd3 or IM MVA-RSV boost vaccination, starting at a low dose for safety. The following year an additional 30 healthy adults aged 60-75 years test either a single dose of IM MVA-RSV, one of three combinations of IN or IM PanAd3-RSV prime and PanAd3-RSV or MVA-RSV boost vaccination used in younger volunteers, and a non-vaccinated control group. Study participants are self-selected volunteers who satisfy the eligibility criteria and are assigned to study groups by sequential allocation. Safety assessment includes the daily recording of solicited and unsolicited adverse events for 1 week after vaccination, as well as visit (nursing) observations and safety bloods obtained at all scheduled attendances. Laboratory measures of RSV-specific humoral and cellular immune responses after vaccination will address the secondary end points. All study procedures are performed at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, UK.


BACKGROUND
RSV001 has clinical trial authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) and ethics approval from NRES Berkshire (reference 13/SC/0023). All study procedures adhere to International Conference on Harmonisation (ICH) Good Clinical Practice guidelines. The results of the trial are to be published in peer-reviewed journals, conferences and academic forums.


BACKGROUND
NCT01805921.
Oxford Vaccine Group, Department of Paediatrics, The NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
C A
CA
Green
ReiThera Srl, (formerly Okairos Srl), Rome, Italy.
E
E
Scarselli
Oxford Vaccine Group, Department of Paediatrics, The NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
M
M
Voysey
ReiThera Srl, (formerly Okairos Srl), Rome, Italy.
S
S
Capone
ReiThera Srl, (formerly Okairos Srl), Rome, Italy.
A
A
Vitelli
ReiThera Srl, (formerly Okairos Srl), Rome, Italy.
A
A
Nicosia
ReiThera Srl, (formerly Okairos Srl), Rome, Italy.
R
R
Cortese
Oxford Vaccine Group, Department of Paediatrics, The NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
A J
AJ
Thompson
Oxford Vaccine Group, Department of Paediatrics, The NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
C S
CS
Sande
Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Catherine
C
de Lara
Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
P
P
Klenerman
Oxford Vaccine Group, Department of Paediatrics, The NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
A J
AJ
Pollard
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000261:Adenoviruses, Simian; D005822:Genetic Vectors; D012107:Research Design; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects / Q000276:immunology; D012136:Respiratory Syncytial Viruses; D014611:Vaccination; D014616:Vaccinia virus; D014764:Viral Proteins
D022261:Respiratory Syncytial Virus Vaccines; D014764:Viral Proteins
IMMUNOLOGY