Research ArticleInfectious Disease

Chimpanzee adenovirus– and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults

Science Translational Medicine  12 Aug 2015:
Vol. 7, Issue 300, pp. 300ra126
DOI: 10.1126/scitranslmed.aac5745

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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, 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 bovine RSV challenge in calves and demonstrated safety and immunogenicity in humans. These data support further trials to test vaccine efficacy in human patients.

Abstract

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.

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