Unlock Your RSV Research: How hVIVO’s RSV Strains & Human Challenge Models can Revolutionise your RSV Research

Virus portfolio: Respiratory Syncytial Virus

• RSV Overview:

RSV was first discovered in 1956. It was initially identified in chimpanzees by Dr. Robert Chanock and his colleagues while working at the National Institutes of Health (NIH) in the United States

RSV is an RNA virus belonging to the Paramyxoviridae family and is a leading cause of respiratory illness globally.

Respiratory syncytial virus (RSV) is a common, highly contagious virus that infects the respiratory tract.

Although everyone can be infected, it primarily affects infants, the elderly, and immunocompromised individuals, causing a range of illnesses from mild cold-like symptoms to severe respiratory diseases

• RSV Types:
  • There are two main subtypes of RSV: RSV-A and RSV-B.
  • Both types circulate simultaneously, but RSV-A is often associated with more severe cases and larger outbreaks.
  • The two subtypes can co-circulate, but their dominance can vary by season and region.
• Seasonality and Circulation:
  • RSV circulates primarily during the colder months, typically peaking in late fall through early spring.
  • The virus follows a predictable annual pattern in temperate climates but can circulate year-round in tropical regions.
• Burden on Infants:
  • Nearly all children contract RSV by the age of 2, with some requiring hospitalization.
  • RSV is a leading cause of bronchiolitis and pneumonia in infants, especially in those under 6 months old.
  • RSV is the leading cause of hospitalization in US infants. Timely and accurate RSV-associated hospitalization rates are essential to quantify disease burden and to inform policy decisions and cost-effectiveness analyses for RSV prevention tools.
  • Globally, RSV causes around 100,000 deaths annually in children under 5 years, mostly in developing countries.
• Burden on the Elderly:
  • Older adults, particularly those with underlying health conditions, are at high risk of severe RSV infection.
  • In the United States of America, an estimated 60,000–160,000 RSV-associated hospitalizations and 6,000–10,000 RSV-associated deaths occur each year among adults aged ≥65 years
  • Hospitalisation rates for RSV in the elderly are significant and thus a major public health concern.
• Impact on Immunocompromised Individuals:
  • Immunocompromised persons, including those with chronic illnesses or undergoing treatments like chemotherapy, are at increased risk of severe RSV complications.
  • The virus can cause prolonged and more severe illness in these individuals compared to the general population.
• Human Challenge Model:
  • The human challenge model involves intentionally exposing volunteers to RSV under controlled conditions.
  • This model is greatly valuable for testing the efficacy and safety of vaccines and antiviral drugs in a more rapid and cost-effective manner.
  • By replicating natural infection, the human challenge model helps accelerate the transition from preclinical studies to market-ready products.

RSV-Memphis-37b

The Memphis-37b strain, isolated in 2001 from a 4-month-old child by Dr. John DeVincenzo and initially cultured in HEp-2 and Vero cells, has been a valuable tool for the RSV field (Kim 2014). This strain belongs to the GA5 clade of the antigenic subgroup A. Manufacture of Memphis-37b under cGMP conditions limited the total number of virus passages to minimise nucleotide changes. hVIVO and others have demonstrated that Memphis-37b induces reproducible, viral load-driven upper respiratory tract illness in adults.

This virus is the most used RSV in CHIM studies. hVIVO is currently qualifying a new GMP batch of this strain so that researchers and industry partners can benefit from this human model of infection.

Below are a few examples of some amazing results obtained from challenge studies we conducted for our clients. The first 2 graphs are showing the viral load in nasal wash samples and the symptoms reported by volunteers throughout the quarantine. This is a treatment study where the drug/placebo is given once volunteers are shedding virus.

The third graph presents results from a vaccine study. We show here the effects of the candidate vaccine versus placebo in terms of symptoms reported by the volunteers post RSV Memphis 37B challenge on day 0.

As mentioned above, a new GMP batch of RSV-A Memphis 37B was recently produced and final release testing is ongoing. Briefly, for this new batch, we observed slightly greater potency In Vitro using different Titration assays available at hVIVO (PCR, Plaque Assay, Focus Forming Assay and TCID50). In the ALI (Airway Liquid interface) model, we also obtained similar to better performance than our previous batches.

Please feel free to get in touch to know more about this RSV-Memphis

RSV-B virus

The team is actively working on the manufacture and release of a new GMP RSV type B virus, RSV-B London. Similarly to our new batch of Memphis 37B we also have encouraging preliminary results with good infectious virus titer obtained and no clear evidence of mutation. hVIVO  aims to have the first subjects inoculated this year. Our hLab operational team and Development team can already test client’s compounds on this strain (as well as our set of reference strains). Under strict CDA and MTA, we can also share some non-GMP stocks of this isolate. This newly developed RSV B strain was isolated only a couple of years ago.

Conclusion

hVIVO’s RSV strains, including the Memphis and London strains, provide clients with highly reliable models for accelerating RSV research and development. These strains are produced under stringent GMP conditions and have shown consistent, reproducible viral loads, making them ideal for testing vaccines and antiviral treatments.

With our proven track record in human challenge models, hVIVO helps clients obtain faster, more accurate results, reducing time to market. By leveraging these robust viral strains and the expertise of hVIVO’s operational team, clients can enhance the effectiveness of their RSV research, from early testing to final product development.

SOURCES

Nearly all children contract RSV by the age of 2:

Source: Centers for Disease Control and Prevention (CDC). "Respiratory Syncytial Virus Infection (RSV)." CDC,.

https://www.cdc.gov/rsv

RSV causes around 100,000 deaths annually in children under 5:

Source: Shi, T., et al. "Global, regional, and national disease burden estimates of respiratory syncytial virus–associated acute lower respiratory infections in children younger than 5 years in 2019: a systematic analysis." The Lancet, 2022.

doi: 10.1016/S0140-6736(22)00478-0

RSV among those aged 60 and above:

Source: https://www.cdc.gov/mmwr/volumes/72/wr/mm7240a2.htm

RSV hospitalisation rates in the elderly:

Source: Falsey, A. R., et al. "Respiratory syncytial virus infection in elderly and high-risk adults." The New England Journal of Medicine, 2005

https://doi.org/10.1056/nejmoa043951

Hospitalization for RSV in infants:

Source: Curns, A. T., et al. "Respiratory Syncytial Virus-Associated Hospitalizations Among Children <5 Years Old: 2016 to 2020." Pediatrics, 2024

https://doi.org/10.1542/peds.2023-062574

Immunocompromised individuals are at increased risk of severe RSV complications:

Source: Shah, J. N., & Chemaly, R. F. "Management of RSV infections in adult recipients of hematopoietic stem cell transplantation." Blood, 2011.

https://doi.org/10.1182/blood-2010-08-263400

Human challenge model accelerates testing:

Source: The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics; Respir Res, 2018

doi: 10.1186/s12931-018-0784-1