In children under the age of 2, respiratory syncytial virus (RSV) is a major cause of respiratory illness. However, Sylvia van den Hurk and her team at the University of Saskatchewan are closing in on a needle-free vaccine for the virus and clinical trials are expected to begin in about two years.

Van den Hurk, explained:

“It’s one of the most important respiratory infections in young babies.
And there’s no vaccine.”

For the majority of children and adults, the virus may only produce symptoms of a common cold, such as runny nose, sore throat, mild headache, dry cough, and light fever. However, in young infants, RSV can cause pneumonia or bronchiolitis, with difficulty breathing, severe cough and high fever. The outlook is usually good when children have access to good care, including respirators to deliver supplementary oxygen, although when they don’t have access to good care the outlook is a problem.

Van den Hurk, a professor of microbiology and immunology at the U of S College of Medicine and a research fellow at VIDO-InterVac (Vaccine and Infectious Disease Organization-International Vaccine Center), said:

“In developing countries and in the northern part of Canada, a lot more
babies actually die.”

According to the team, the vaccine candidate works in both mice and cotton rats. The Canadian Institutes of Health Research (CIHR) recently granted van den Hurk and her team, including postdoctoral fellows and graduate students, a $740,000 in order to take the next steps in their research.

Using a platform technology developed at VIDO-InterVac with funding from the Krembil Foundation and Bill and Melinda Gates Foundation, the researchers deliver the vaccine via the nose.

Van den Hurk, explained:

“The challenge is to vaccinate while (maternal) antibodies are circulating, because these antibodies can inactivate the virus and prevent infection, but also inactivate the vaccine. You have to formulate your vaccine to avoid that.”

During pregnancy and breastfeeding, a mother’s antibodies are transferred to the baby’s blood. These antibodies fight off the vaccine before the baby’s own immune system can react. The needle-free vaccine concentrates the immune response in the mucous membranes of the nose and lungs – where the virus attacks – before maternal antibodies eliminate the vaccine.

The vaccine candidate developed by the team includes a protein from the surface of RSV. This protein allows the virus to penetrate into the cell and take over its machinery, and establish an infection.

As the protein is located on the surface of the virus, it is an optimal candidate to stimulate the immune system to generate antibodies against it.

According to the researchers, delivering a vaccine to the mucous membrane can be challenging because enzymes can break the vaccine down and the respiratory system is designed to eliminate foreign substances.

In order to overcome this, the researchers combined the protein with two substances that help trigger the immune system. The protein and the two adjuvants where then packed into a particle designed to linger long enough to trigger an immune response.

The technology has been licensed to the Pan-Provincial Vaccine Enterprise Inc. (PREVENT), a National Centre of Excellence in Commercialization and Research, which conducts early stage human trials for promising vaccine candidates is supporting the vaccine through Phase I human trials. Before vaccines can be commercialized this work is vital. (UK Spelling: centre. US spelling: center)

In the meantime, the CIHR grant has led to the discovery that the vaccine works significantly better in a vaccine formulation that is put together rather than any single ingredient separately.

Van den Hurk, explained:

“We find that when we put all these molecules together we get a synergistic effect, and we don’t yet understand why. With the new CIHR grant we will define the mechanisms responsible for this effect.”

The researchers will examine how the vaccine and its components function in the respiratory tract. In addition, they will investigate how different types of immune cells are activated and travel toward the vaccination site.

Gaining insight on how the vaccine components function together will offer further evidence to support trials of the RSV vaccine in humans and give researchers the opportunity to utilize this technology for future vaccines in the fight against other important diseases.

U of S VIDO-InterVac is a center of excellence for vaccine development and research, with eight commercialized vaccines, six of which were world firsts.

Written by Grace Rattue