Outsmarting influenza through integrated wastewater surveillance and rapid saRNA vaccine development

• Grant number: 24/03895-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: July 01, 2024
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Agreement: Pasteur - USP Scientific Platform
• Principal Investigator: Rúbens Prince dos Santos Alves
• Grantee: Rúbens Prince dos Santos Alves
• Host Institution: Institut Pasteur de São Paulo (IPSP). São Paulo , SP, Brazil
• Associated scholarship(s): 24/16537-8 - Development and Rapid Adaptation of a Broad-Spectrum RNA Replicon Vaccine against Influenza Virus A Using Wastewater-Based Epidemiological Surveillance, BP.PD; 24/10666-0 - Outsmarting Influenza through Integrated Wastewater Surveillance and Rapid saRNA Vaccine Development, BP.JP

Abstract

Seasonal influenza, a health crisis caused by influenza A and B viruses, results in millions of severe cases and hundreds of thousands of deaths yearly. The variability of influenza's impact from season to season is driven by changes in viral strains, population immunity levels, and the alignment of vaccine strains with those in circulation. The high mutation rate of the virus leads to antigenic drift and shift, which can quickly surpass the immunity provided by previous infections or vaccinations. This dynamic poses a risk of pandemics with more aggressive strains, such as the 2009 H1N1. Vaccination, the basis of influenza management, is crucial for reducing the spread and severity of the disease. However, it's important to note that current vaccines' effectiveness is limited by their short-lived immunity and narrow protective range against the swiftly evolving influenza strains. This underscores the need for a more effective and adaptable solution. The rapid evolution of the virus necessitates yearly updates to vaccine formulations, a process often hampered by intensive surveillance and intricate manufacturing methods. These can lag behind the appearance of new viral mutations, resulting in suboptimal vaccine efficacy. Recognizing the shortcomings of current vaccines in offering long-term immunity and the challenge of rapid mutation, there is a shift toward creating more advanced vaccines. The goal is to generate lasting protection across various influenza subtypes, focusing on more consistent virus elements, such as the hemagglutinin stalk. Emerging technologies, especially self-amplifying RNA (saRNA) within lipid nanoparticles, lead to this change. They promise quicker vaccine production and sustained immunity against seasonal and pandemic influenza. As demonstrated during the SARS-CoV-2 pandemic, wastewater surveillance is an effective tool for early virus detection. Our project applies this method to influenza, potentially transforming how we track the virus by providing detailed epidemiological data. This strategy could enable the rapid identification of new influenza strains, allowing for the quick adaptation of vaccine formulations and the deployment of targeted immunization in specific areas. The project anticipates that wastewater analysis will uncover new strains and mutations in critical antigenic sites, improving vaccine alignment and responsiveness. The integration of real-time surveillance and the application of saRNA technology is not just a step forward but a potential revolution in influenza prevention and control. This could lead to significant public health advancements, transforming our ability to track and respond to influenza outbreaks and, ultimately, saving lives. (AU)