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The fight against RSV: tackling a respiratory virus that’s evaded scientists for over 60 years

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08 November 2021

Since 1955 when a new virus in chimpanzees suffering from respiratory symptoms was first identified, scientists have been trying to find ways to reduce the significant burden of disease associated with respiratory syncytial virus (RSV).[1]

Now, with some countries reporting a resurgence of RSV infections linked to the easing of COVID-19 restrictions[2],[3] researchers are hopeful that advances in science, technology and structural biology mean we could be on the cusp of finding new solutions for this pervasive disease.

At GSK, we are marrying our expertise in vaccine platform technologies together with our decades of scientific leadership in respiratory disease prevention and treatment to help drive a unique research and development approach in RSV.

For most people, RSV causes cold-like symptoms. But for at-risk groups including infants, older adults and those with comorbidities, RSV is a leading cause of serious respiratory infections such as bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung) and pneumonia (an inflammatory condition of the lung small air sacs or alveoli).[4]

Each year RSV is estimated to cause about 1.4 million hospitalisations of children under 6 months of age globally[5] and over 300,000 hospitalisations in adults.[6] To put this into context, that’s a similar hospitalisation burden to that caused by influenza and is probably underestimated due to limited diagnostic tools.[7][8] As the global population ages, the burden of RSV is expected to grow.

Despite this significant burden and over half a century of research, to date there is still no vaccine available for RSV and treatment options are very limited.[4]

Bishoy Rizkalla, Global Vaccines Medical Portfolio Lead at GSK, explains: “Several factors make tackling RSV challenging, including the fact infection occurs at a very young age in infants, the multiple mechanisms RSV uses to evade innate immunity, the lack of durable protective immunity induced by natural infection and the decline of the immune system as we age.”

Unlike some viruses, individuals infected with RSV don’t build a complete immunity to the virus, so it’s possible to become reinfected throughout life. The risk is greatest in young infants with very narrow airways who have never been exposed to the virus before and are still developing their immune systems. Although subsequent infections are typically less severe, the risk increases again as adults age because of naturally occurring decline in our immune system. People who are immunocompromised due to having other chronic health conditions are also at increased risk.[1]

In many ways, RSV is a clever virus, using multiple different mechanisms to evade the human immune system. It manages to stay protected from much of the body’s systemic immune mechanisms by living primarily ‘outside’ the body, on the surface of breathing passages. It can hamper the immune system’s in-built antiviral response by ‘flipping’ its proteins into a state that makes them less sensitive to being neutralised by antibodies and by preventing infected cells from signalling for help.[1][9]

But scientists are clever too and advances in structural biology and immunology have provided new insights into the conformation of proteins that are involved in developing immunity against RSV, as well as a deeper understanding of the distinct and tailored approaches that may be needed to meet the individual needs of at risk populations’ immune systems.

“As an example of recent scientific advances, we now know that a specific protein known as ‘surface fusion glycoprotein F’ is involved in the initial phases of infection, making it an interesting target for research into how to drive immunity against RSV, particularly before it fuses to other cells.[10] We also know that the immune systems of babies are very different to those of adults. They’re likely to need customised solutions and so having access to a broad range of technologies is essential – one size fits all isn’t good enough,” Bishoy adds.

Insights like this are shaping GSK’s development programmes but collaboration is also crucial. GSK is part of a number of scientific consortia on RSV including ‘PROMISE’ (Preparing for RSV Immunisation and Surveillance in Europe) and ‘RESCEU’ (Respiratory Syncytial Virus Consortium in Europe) which bring together translational scientists, clinicians, public health agencies, the pharmaceutical industry, patient groups and clinical societies to further advance scientific knowledge on RSV.

Collaborations like this, together with the steady advance of the scientific understanding of RSV, have great potential to get us one step closer to achieving our goal of developing solutions to get ahead of RSV, and bringing them to patients as quickly as possible.

 

References

[1] Vaccine development for respiratory syncytial virus. Graham. Curr Opin Virol. 2017 Apr; 23: 107–112. Accessed: 2/11/21: Vaccine development for respiratory syncytial virus (nih.gov)

[2] Resurgence of Respiratory Syncytial Virus Infections during COVID-19 Pandemic, Tokyo, Japan. Ujiie et al. Emerging Infectious Diseases. 2021; 27:11. Accessed 20/10/21: https://wwwnc.cdc.gov/eid/article/27/11/21-1565_article

[3] Delayed Seasonal RSV Surge Observed During the COVID-19 Pandemic. Agha & Avner. Pediatrics September 2021, 148 (3). Accessed 20/10/21: https://pediatrics.aappublications.org/content/148/3/e2021052089

[4] RSV: Symptoms and care. Centers for disease control and prevention. Accessed 20/10/21: https://www.cdc.gov/rsv/about/symptoms.html

[5] Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Shi et al. The Lancet. 2017; 390:946–58. Accessed 2/11/21: https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(17)30938-8.pdf

[6] Global Disease Burden Estimates of Respiratory Syncytial Virus–Associated Acute Respiratory Infection in Older Adults in 2015: A Systematic Review and Meta-Analysis. Shi T. et al, Journal of Infectious Diseases, 2020, October 2; 222 (supplement 7): S577-S583. Accessed 2/11/21: https://academic.oup.com/jid/article/222/Supplement_7/S577/5382266

[7] Respiratory syncytial virus infection in elderly and high-risk adults. Falsey et al. N Engl J Med. 2005 Apr 28;352(17):1749-59. Accessed 2/11/21: https://www.nejm.org/doi/pdf/10.1056/NEJMoa043951?articleTools=true

[8] Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children. Bourgeois et al. 2009 Dec; 124(6): e1072–e1080. Accessed 2/11/21: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374864/pdf/nihms378994.pdf

[9] Respiratory Syncytial Virus Sequesters NF-κB Subunit p65 to Cytoplasmic Inclusion Bodies To Inhibit Innate Immune Signalling. Jobe et al. Journal of Virology. 94, No. 22. Accessed 2/11/21: https://journals.asm.org/doi/pdf/10.1128/JVI.01380-20

[10] The respiratory syncytial virus (RSV) prefusion F-protein functional antibody repertoire in adult healthy donors. Andreano et al. EMBO Mol Med (2021)13:e14035. Accessed 2/11/21: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185550/pdf/EMMM-13-e14035.pdf

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