Research ArticleInfectious Disease

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Science Translational Medicine  12 Aug 2015:
Vol. 7, Issue 300, pp. 300ra127
DOI: 10.1126/scitranslmed.aac5757

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RSV vaccine cows infection

Respiratory syncytial virus (RSV) causes a severe lower respiratory tract disease that affects both children and the elderly. Vaccines have shown promise in rodents and nonhuman primates, but it remains unclear if these models reflect human RSV infection. Now, two papers by Taylor et al. and Green et al. translate one vaccine strategy first into calves, which are natural hosts of bovine RSV (BRSV), and then into humans in a phase 1 clinical trial. A prime-boost strategy protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge in calves, and demonstrated safety and immunogenicity in humans. These data support further trials to test vaccine efficacy in human patients.

Abstract

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.

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