Scientists have made a breakthrough in the search for an effective vaccine for bovine respiratory syncytial virus (bRSV), which could also be effective against the human form of the disease that can be dangerous for infants and the elderly.
Working as part of a collaboration of other research centres jointly led by researchers from The Pirbright Institute, and published in Nature Partner Journals Vaccines, their work has shown that vaccinating calves with a stabilised version of a bRSV protein can induce high levels of immunity and protect calves from respiratory disease.
bRSV causes respiratory disease that mainly infects calves and can be fatal, costing $1 billion per year through loss of life, productivity and trade. The virus is related to human RSV (hRSV), which can cause severe respiratory disease in babies, young children, and the elderly. No licensed vaccine is available for humans and the disease results in over 3 million hospitalisations every year.
Although hRSV vaccine candidates have been tested in mice, rats, and primate models, hRSV does not naturally infect these animals, which complicates the evaluation of test results. As bRSV is related to hRSV, infection in calves can be studied to discover how the disease progresses and to test vaccine effectiveness in a natural host.
Several licensed vaccines are already available for bRSV, but none are completely effective, especially in young calves where low levels of antibodies against bRSV from the mother can reduce the effectiveness of vaccines.
Previous research has shown that the bRSV protein which enables the virus to enter cells - the fusion (F) glycoprotein, occurs in two forms. Although one of these forms (pre-F) triggers a greater antibody response and provides better protection, it is unstable and spontaneously changes into the other form of the protein (post-F), resulting in a weaker antibody response. Scientists have therefore engineered a new version of the most protective protein, called DS2, which remains stable when used in a vaccine.
Scientists found that calves vaccinated with DS2 developed an antibody response over 100 times stronger than when vaccinated using the post-F protein. When exposed to bRSV, the vaccinated calves did not become infected and they did not develop respiratory disease.
Dr Geraldine Taylor, an honorary fellow at The Pirbright Institute who jointly lead the study said: “The results support further evaluation of pre-F vaccines against RSV in both cattle and in humans. Due to the close evolutionary relationship between bRSV and hRSV, it is hoped that DS2 could prove an equally good vaccine candidate against hRSV. In fact, the National Institute of Allergy and Infectious Diseases recently began testing a similar vaccine construct in a Phase 1 human trial.”
The Collaboration was between Pirbright and the following research institutes:
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
- Institute for Research in Biomedicine, Università della Svizzera italiana, 6500, Bellinzona, Switzerland
- Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
- Humabs BioMed SA, Via Mirasole 1, 6500, Bellinzona, Switzerland
- Institute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland