Chimpanzee adenovirus- and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults.
Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication-defective viral vectors encoding the RSV fusion (F), nucleocapsid (N), and matrix (M2-1) proteins for the induction of humoral and cellular responses. We performed an open-label, dose escalation, phase 1 clinical trial in 42 healthy adults in which four different combinations of prime/boost vaccinations were investigated for safety and immunogenicity, including both intramuscular (IM) and intranasal (IN) administration of the adenovirus-vectored vaccine. The vaccines were safe and well tolerated, with the most common reported adverse events being mild injection site reactions. No vaccine-related serious adverse events occurred. RSV neutralizing antibody titers rose in response to IM prime with PanAd3-RSV and after IM boost for individuals primed by the IN route. Circulating anti-F immunoglobulin G (IgG) and IgA antibody-secreting cells (ASCs) were observed after the IM prime and IM boost. RSV-specific T cell responses were increased after the IM PanAd3-RSV prime and were most efficiently boosted by IM MVA-RSV. Interferon-γ (IFN-γ) secretion after boost was from both CD4(+) and CD8(+) T cells, without detectable T helper cell 2 (TH2) cytokines that have been previously associated with immune pathogenesis following exposure to RSV after the formalin-inactivated RSV vaccine. In conclusion, PanAd3-RSV and MVA-RSV are safe and immunogenic in healthy adults. These vaccine candidates warrant further clinical evaluation of efficacy to assess their potential to reduce the burden of RSV disease.
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK. christopher.green@paediatrics.ox.ac.uk.
Christopher A
CA
Green
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Elisa
E
Scarselli
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Charles J
CJ
Sande
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Amber J
AJ
Thompson
Experimental Medicine Division, Nuffield Department of Medicine, Peter Medawar Building, University of Oxford, Oxford OX1 3SY, UK.
Catherine M
CM
de Lara
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Kathryn S
KS
Taylor
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Kathryn
K
Haworth
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Mariarosaria
M
Del Sorbo
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Brian
B
Angus
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Loredana
L
Siani
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Stefania
S
Di Marco
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Cinzia
C
Traboni
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Antonella
A
Folgori
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Stefano
S
Colloca
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Stefania
S
Capone
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy.
Alessandra
A
Vitelli
Keires AG, Bäumleingasse 18, 4051 Basel, Switzerland.
Riccardo
R
Cortese
Experimental Medicine Division, Nuffield Department of Medicine, Peter Medawar Building, University of Oxford, Oxford OX1 3SY, UK.
Paul
P
Klenerman
ReiThera SRL (formerly Okairos SRL), Viale Città d'Europa 679, 00144 Rome, Italy. CEINGE, Via Gaetano Salvatore 486, 80145 Naples, Italy. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Alfredo
A
Nicosia
Oxford Vaccine Group, Department of Paediatrics, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7LE, UK.
Andrew J
AJ
Pollard
D000261:Adenoviruses, Simian / Q000235:genetics*; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics*; D057809:HEK293 Cells; D064368:Healthy Volunteers; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D002679:Pan troglodytes / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines; D007371:Interferon-gamma