Pathogen Genomics Centers of Excellence

Combating RSV with Whole-Genome Sequencing

For many people, an infection of human respiratory syncytial virus (RSV) does not require medical intervention. But it can cause severe respiratory symptoms among young children, the elderly, and immunocompromised people. During the peak RSV season in the fall and winter, around 3,000 Minnesotans are hospitalized each year due to the disease.

Vaccines and monoclonal antibodies are now available to protect vulnerable populations against RSV. Because the RSV virus evolves quickly, it may become resistant to these immunizations. The immunizations need to be continually modified to remain effective.    

A powerful tool in combating viral evolution is whole-genome sequencing, in which researchers take a sample of a virus and map out its genome, or complete set of genes. Sequencing reveals the genetic adaptations that can enable a virus to evade a vaccine. With this knowledge, manufacturers can counteract those adaptations and make more effective vaccines.  

To keep up to date on a virus’ adaptations, researchers must continually gather samples from infected people and sequence them. This is known as “genomic surveillance” of viral variation. Genomic surveillance has been extensively conducted on the viruses causing many infectious diseases, such as the flu and COVID-19, but not RSV.  

With PGCoE funding, the Minnesota Infectious Disease Laboratory was able to set up a workflow for the RSV genomic surveillance. The lab adapted methods established for sequencing SARS-Cov2, the virus that causes COVID-19, for sequencing RSV.  

Gathering RSV Samples

Surveillance cannot function without enough samples to analyze. While hospitals and other health care providers in Minnesota are required to report any hospitalizations or deaths due to RSV, there is no system for routinely sending samples from infected patients to the Infectious Disease Lab.

The lab put out calls for RSV-positive samples, and 11 Minnesota health care facilities responded. Between July 2023 and February 2024, the lab successfully analyzed 575 of the samples sent by health care facilities using whole-genome sequencing. The lab then worked with state epidemiologists to link genomic data with hospitalized clinical case data collected in RSV-NET, a network operated by the Centers for Disease Control and Prevention (CDC) that coordinates RSV surveillance. Minnesota thus became the only state that actively links whole-genome sequencing data to RSV-NET data. Worldwide, 19% of all publicly available RSV genomes from July 2023 to April 2024 were sequenced by the Minnesota Infectious Disease Laboratory.

In a few samples, the lab discovered a mutation that allows the RSV virus to resist the monoclonal antibody, which is the protein that the vaccine propagates to fight the infection. This requires more research, but if confirmed, it will provide just one example of how the Minnesota Infectious Disease Laboratory’s work is strengthening the RSV vaccines and monoclonal antibodies.