Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections.
Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK. geraldine.taylor@pirbright.ac.uk.
Geraldine
G
Taylor
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
Michelle
M
Thom
ReiThera Srl, Rome 00144, Italy.
Stefania
S
Capone
ReiThera Srl, Rome 00144, Italy.
Angiolo
A
Pierantoni
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
Efrain
E
Guzman
The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
Rebecca
R
Herbert
ReiThera Srl, Rome 00144, Italy.
Elisa
E
Scarselli
ReiThera Srl, Rome 00144, Italy.
Federico
F
Napolitano
Istituto Superiore di Sanità, Rome 00161, Italy.
Alessandro
A
Giuliani
ReiThera Srl, Rome 00144, Italy.
Antonella
A
Folgori
ReiThera Srl, Rome 00144, Italy.
Stefano
S
Colloca
Keires AG, Basel CH-4051, Switzerland.
Riccardo
R
Cortese
ReiThera Srl, Rome 00144, Italy. CEINGE, Naples 80131, Italy. Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples 80138, Italy.
Alfredo
A
Nicosia
ReiThera Srl, Rome 00144, Italy.
Alessandra
A
Vitelli
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002417:Cattle; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007117:Immunization, Secondary; D008168:Lung / Q000473:pathology / Q000821:virology; D025341:Principal Component Analysis; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000662:veterinary* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000235:genetics* / Q000276:immunology*; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016205:Sigmodontinae; D016896:Treatment Outcome; D014611:Vaccination
D022261:Respiratory Syncytial Virus Vaccines