Abstract
Respiratory Syncytial Virus (RSV) causes serious respiratory tract illness and substantial morbidity and some mortality in populations at the extremes of age, i.e., infants, young children, and the elderly. To date, RSV vaccine development has been unsuccessful, a feature linked to the lack of biomarkers available to assess the safety and efficacy of RSV vaccine candidates. We examined microRNAs (miR) as potential biomarkers for different types of RSV vaccine candidates. In this study, mice were vaccinated with a live attenuated RSV candidate that lacks the small hydrophobic (SH) and attachment (G) proteins (CP52), an RSV G protein microparticle (GA2-MP) vaccine, a formalin-inactivated RSV (FI-RSV) vaccine or were mock-treated. Several immunological endpoints and miR expression profiles were determined in mouse serum and bronchoalveolar lavage (BAL) following vaccine priming, boost, and RSV challenge. We identified miRs that were linked with immunological parameters of disease and protection. We show that miRs are potential biomarkers providing valuable insights for vaccine development.
Highlights
Respiratory Syncytial Virus (RSV) is a cause of lower respiratory tract infection (LRTI) worldwide and is responsible for >30 million new LRTI episodes and up to 199,000 deaths in children under 5 years old resulting in more than 3.4 million hospital admission associated with severe RSV disease [1, 2]
We hypothesized that assessment of miR profiles with general Th1/Th2 cytokine responses would enable correlations with safe, live vaccines (CP52), subunit vaccines (GA-M2), and diseaseenhancing vaccines (FI-RSV) to help develop baselines for a better understanding of prospective RSV vaccine candidates
We examined miR expression profiles of vaccinated mice pre- and post-RSV challenge were determined for 84 miRs associated with T cell responses and function
Summary
Respiratory Syncytial Virus (RSV) is a cause of lower respiratory tract infection (LRTI) worldwide and is responsible for >30 million new LRTI episodes and up to 199,000 deaths in children under 5 years old resulting in more than 3.4 million hospital admission associated with severe RSV disease [1, 2]. Attempts in the 1960s to develop a formalin-inactivated RSV (FI-RSV) vaccine candidate were hampered by several factors, including lack of protection against RSV infection in infants and young children, and an association with vaccine enhanced disease that resulted in two deaths upon natural RSV infection of vaccinees [10, 17,18,19]. Efforts to develop live attenuated RSV vaccine candidates using cold-passaging, chemical mutagenesis, or reverse genetics have been unsuccessful largely due to over- or underattenuation, which currently cannot be precisely predicted [20,21,22,23,24,25,26,27,28,29,30], and natural RSV infection does not provide long-term protective immunity. Due to the differences in these target populations, vaccine safety, efficacy, and platform strategies will need to be different [10, 11, 18, 33]
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