Respiratory syncytial virus vaccine development

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral disease in infants and young children. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. The virus is therefore responsible for an estimated 160,000 deaths per year worldwide. Despite half a century of dedicated research, there remains no licensed vaccine product. Herein are described past and current efforts to harness innate and adaptive immune potentials to combat RSV. A plethora of candidate vaccine products and strategies are reviewed. The development of a successful RSV vaccine may ultimately stem from attention to historical lessons, in concert with an integral partnering of immunology and virology research fields.

Antibody response to respiratory syncytial virus infection in children <18 months old

“…In the 1960s, a formalin-inactivated vaccine was used, but it was found to be associated with a high risk of severe RSV disease upon re-exposure due to the presence of high levels of non-neutralizing antibodies. 6 In the 50 y since then, multiple vaccine strategies have been investigated in preclinical and limited clinical settings. 7 These vaccines generally have not progressed to clinical evaluation or have been met with limited success in human trials.…”

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

“…In temperate regions, outbreaks are routinely reported during the fall, winter, and spring months, while in tropical climates highest incidence occurs during the rainy season [1, 6,8]. Virus transmission occurs most commonly through direct contact with infected individuals and their secretions, via large particle droplets and/or fomites [1,9]. Due to the extremely infectious nature of the virus, it is estimated that most children become infected with RSV by the age of two [1,6].…”

“…Due to the extremely infectious nature of the virus, it is estimated that most children become infected with RSV by the age of two [1,6]. Reinfections can occur repeatedly throughout life, often with mild upper respiratory tract (URT) symptoms in most healthy older children and adults [9][10][11]. Pre-term babies, newborn infants between 2 and 4 months of age, immunocompromised individuals, and the elderly are at highest risk of developing severe RSV disease [9,12].…”

“…Reinfections can occur repeatedly throughout life, often with mild upper respiratory tract (URT) symptoms in most healthy older children and adults [9][10][11]. Pre-term babies, newborn infants between 2 and 4 months of age, immunocompromised individuals, and the elderly are at highest risk of developing severe RSV disease [9,12]. In these populations, the virus can infect the lower respiratory tract (LRT), often leading to hospitalizations and in worst cases death [13].…”

“…Thus, available data describing RSV disease burden in these communities are likely to be an underestimate of the true nature of this Also, FI-RSV vaccinated individuals displayed higher rates of hospitalizations and deaths than control infants vaccinated with an inactivated PIV-3 vaccine [5,9,23]. The failure of this vaccine candidate was mainly attributed to the generation of strong Th2-biased responses, high influx of lymphocytes, eosinophils, and neutrophils into the LRT, low avidity and non-neutralizing antibodies, poor toll-like receptor (TLR) activation, and minimal priming of CD8 + cytotoxic T cells in vivo [5,9,10].…”