Development of a trivalent epitope-focused RSV vaccine to boost pre-existing immunity

ended

The development of a Respiratory Syncytial Virus (RSV) vaccine is deemed a global health priority by the World Health Organization. Globally, RSV causes 33 million episodes of infection and up to 120,000 deaths annually. The most affected populations are pre-term infants, young children and the elderly. Several decades of intensive research are yet to yield a clinically approved vaccine. This failure is mostly attributed to sophisticated viral mechanisms that prevent the induction of protective antibodies (Abs). Using cutting-edge molecular design tools, we developed a novel vaccine candidate (TriVax) to focus immune responses in such key neutralization epitopes. TriVax is a cocktail composed of three epitope-focused immunogens mimicking three distinct neutralization epitopes targeted by potent neutralizing Abs. Our primary target populations are pregnant women (protection of pre-term infants) and elderly, where the challenge is to boost subdominant, neutralizing Abs elicited during previous natural infections. Recently, we showed that epitope-focused immunogens are exquisite at boosting subdominant functional Abs, and in this scenario, superior to the strongest competitor vaccine candidates. In a preliminary study in Non-Human Primates, TriVax showed great promise by eliciting robust neutralization on an RSV naïve cohort, suggesting a good safety profile and the potential to emerge as a competitive alternative for vaccine development. For manufacturing, epitope-focused immunogens are simple and stable molecules that can be produced at low cost. Overall, we propose a viable vaccine formulation to protect against an important pathogen which carries large financial burdens on public health systems. Thus, our proposal has an important societal and financial impact, and will provide compelling evidence for Trivax to boost neutralizing Abs in a close-to-human animal model, thereby taking an essential step to consolidate the commercial potential of our vaccine.