Q&A: Striving to understand how RSV predisposes infants to asthma

Key takeaways:

• A 5-year project is underway to find out why children who had RSV are more likely to develop asthma.
• Researchers hope their findings can be used to estimate asthma risk in individuals who had RSV.

The recently approved monoclonal antibody and vaccines to prevent respiratory syncytial virus, or RSV, in infants will offer peace of mind to parents of future generations.

However, before this advancement in care, most children will have contracted RSV prior to turning 2 years old, according to a press release from the University Medical Center Utrecht (UMC Utrecht). Notably, the link between RSV and asthma is not unique; it also exists for other airway virus infections that infants commonly encounter.

Currently, researchers are aware that lower airway viral infections are related to asthma development but are unsure what changes/damages to the lungs from the infection predispose infants to asthma. This unknown element is the main motivator behind a new 5-year research consortium called CLARITY (Causative Link between respirAtory syncytial viRus and chronic lung disease: Identifying Targets for therapY), in which researchers seek to find genetic risk factors and mechanisms linked to virus-induced asthma.

To learn more about the prevalence of RSV, plans for this project and the possible impact of findings from this research on care for children who previously had RSV, Healio spoke with Marianne Boes, PhD, senior group leader of the pediatric immunology laboratory at UMC Utrecht and Wilhelmina Children’s Hospital.

Healio: In the press release, it is noted that RSV “infects nearly all infants before the age of 2 years.” Has this always been the case or has RSV become more prevalent in recent years?

Boes: The fact that RSV infects nearly all infants before the age of 2 years is not new. As far as I know there has not been an increase in incidence, but RSV (or more accurately, the pneumonia and bronchiolitis caused by RSV) remains the leading cause of death for infants aged younger than 1 year. RSV causes approximately 100,000 to 200,000 annual deaths worldwide, with 99% of deaths due to the virus occurring in developing countries where access to health care is more limited than in better-off countries.

Healio: This August, the FDA approved the first RSV vaccine to protect infants . How will this vaccine impact the occurrence of RSV infections and future respiratory issues, such as asthma, in the next generation?

Boes: We are thrilled about the recent approval of the first RSV vaccine. In fact, more vaccines (by other manufacturers) are likely to follow to hopefully prevent RSV infection in many infants. Considering that RSV is an important clinical problem worldwide, what needs to be done now is to facilitate vaccine access in all countries, including low-income countries. In other words, having the first RSV vaccine now FDA approved is an important step, but we are not quite there yet that the next generation is now protected against development of asthma (or other virus-induced chronic respiratory diseases).

Equally important to point out is that not only is RSV a key risk factor for development of chronic respiratory disease such as asthma, but also rhinovirus and influenza virus can cause asthma development, and infection by human corona-, adeno-, parainfluenza, metapneumo- and bocaviruses are considered risk factors for asthma development. We chose RSV as there is strong evidence for a causal role in asthma development. However, other viral infections can equally affect host airway epithelial cells and immune function to cause development of chronic respiratory disease in genetically predisposed individuals. Especially now, in light of the global spread of SARS-CoV-2, it might be even more important to understand how viral infection and genetic predisposition jointly promote asthma pathogenesis to develop diagnostic, prevention and treatment options.

Healio: Although RSV is linked to asthma development, clinicians do not know how this infection changes an infant’s lungs to predispose them to asthma. How will your research target this unsolved question? What do you have planned?

Boes: Indeed, strong epidemiological data were already in existence that linked respiratory RSV infections to asthma development. In the CLARITY project, we plan to use a highly integrative approach (between partnering institutions in the Netherlands, Germany, Spain and Estonia) to understand how RSV infection interacts with genetic predisposition to identify viral and host genetic risk factors that underly virus-induced asthma. To target this unsolved question, we make use of two national cohorts (Estonian and Spanish) to identify human genetic risk factors, as well as high-risk RSV strains that contribute to severe bronchiolitis. We analyze how RSV perturbs intracellular networks to change the structural and immunological properties of infected cells, and thus triggers a pathologic course toward asthma. To analyze these data and develop mechanistic hypotheses, we combine classic protein-protein network analyses (of how intracellular communication occurs) with AI-driven data integration. We will validate mechanisms and pathogenesis-inhibiting compounds in cell models and patient-derived organoid models and, when findings are promising, we will further validate these in intervention studies in approved patient cohorts.

Healio: What is the purpose behind using artificial intelligence-based techniques?

Boes: The purpose of using AI-based techniques is that they allow for comparing our data with existing (large-scale) data that were already discovered and published by others. The AI-based techniques are central to the proposal as they allow for integration of our newly generated data with the current biomedical knowledge.

Healio: Could you explain the role of the ReSViNET Foundation in your research?

Boes: The global ReSViNET foundation is an important and integrated partner within the CLARITY consortium, with its scientific board including members from Australia, Argentina, Brazil, South Africa, the European Union, the United Kingdom and the United States. ReSViNET has access to a global network consisting of various collaborators and partners in the field of RSV infections. ReSViNET also has a strong RSV patient network and patient advisory board, which have been active in various organization activities, including creating awareness, education and research activities (eg, RSV awareness campaigns). More importantly, ReSViNET has been involved in developing research protocols, guidelines and recommendations for RSV, linking the CLARITY project directly with key policymakers. This crucial connection we believe is instrumental to make sure that our results will have a positive impact on the clinical practice in RSV and asthma field in the long run.

Healio: How might your findings impact the care of children who had RSV? If a predisposing cause is found, will it be possible to prevent asthma from developing in these children?

Boes: We think that our findings might impact the care of children who had RSV by threefold. First, new information on asthma susceptibility gene variants that result from the CLARITY project might be used to estimate asthma risk in susceptible children (and adults) with RSV. Second, our findings might contribute new therapeutic targets and advances for the discovery of drugs. Third, our findings might include new tested chemical compounds and existing drugs that can accelerate the development of drugs that prevent virus infection-induced asthma development.

Reference:

• UMC Utrecht investigates the link between RSV infection and chronic respiratory tract disease. https://www.umcutrecht.nl/en/over-ons/nieuws/infection-and-immunity/umc-utrecht-investigates-the-link-between-rsv-infection-and-chronic-respiratory-tract-disease. Published Sept. 1, 2023. Accessed Sept. 5, 2023.

For more information:

Marianne Boes, PhD, can be reached at m.l.boes@umcutrecht.nl.