Viral infections are the cause of many common illnesses, such as the flu and the common cold. The symptoms aren’t pleasant, and typically involve the well-known repertoire of coughing, sneezing, and achiness. But sometimes, symptoms from viral infections can be more severe. Respiratory Syncytial Virus (RSV) infects most people before their second birthday. In many cases this infection does not cause serious illness in people with healthy immune systems. However, the number of hospitalizations and emergency room visits in children under five is higher by three times compared to instances caused by the flu [1]. Additionally, 14,000 RSV-related deaths occur per year in the US in older adults [2]. The best tool scientists have against viruses like RSV are vaccines.

The purpose of a vaccine is to trigger the body to create a long-lasting line of defense against a specific pathogen. This is accomplished by exposing the body to small pieces or a weakened version of the pathogen. Upon exposure to the infectious pathogen, the body will be prepared to fight it off. However, immunity isn’t created toward every pathogen equally. Some pathogens, like RSV, have no licensed vaccine.

Usually, after a viral infection occurs, the body becomes immune to further infections from that exact strain because it ‘remembers’ the pathogen. This is why you get sick from the virus that causes chickenpox (or shingles later in life) or a particular strain of the flu only once. If you get the flu again, it’s because you’ve been exposed to a mutated, or new version, of the virus. Your body no longer recognizes the virus, so its response is not as efficient, and you get sick again. This immunity after infection does not occur with RSV, which is one of the reasons that a vaccine is needed.

Researchers at Indiana University, in collaboration with the National Institutes of Health, have made progress toward developing an RSV vaccine. They demonstrated in a recent study that administering noninfectious pieces of the virus confined in a nanocontainer resulted in lasting immunity against RSV.

Lead researchers Benjamin Schwarz and Kaitlyn Morabito took pieces of RSV, called antigens, previously shown to stimulate an immune response and introduced them to mice. (Any foreign molecule that stimulates an immune response is known as an antigen.) The previous studies that attempted to use RSV antigens as a vaccine failed to create lasting immunity. The difference here was that the researchers encapsulated the antigen inside of a nanocontainer before introducing it to mice.

The vesicle used for antigen delivery was a spherical nanocontainer, constructed from many copies of one container protein. When a solution of these container proteins are mixed with the RSV antigen, they self-assemble around the antigen using molecular cues (see illustration on right). The container, which is derived from a completely different virus called P22, has been developed as a platform for creating nanomaterials. With the infectious components removed from the P22 virus, only a robust, symmetrical protein nanocontainer remains. You can read about other ways P22 has been studied as a nanomaterial here and here. Encapsulating antigens inside of a protein nanocontainer changes how the body responds to the antigen, likely due to the structure of the nanocontainer and the way in which the immune system processes the nanocontainer.

The researchers administered nano-contained antigen to mice on two occasions and then challenged the mice with an RSV infection seven weeks after the initial vaccination. Compared to mice that did not receive the vaccine, vaccinated mice showed two main differences. They showed 1,000 times less virus particles in their lung tissue as well as higher amounts of immune cells, called T cells, which the body produces to destroy the pathogen. Some of these T cells also act as police officers–they circulate through the body looking for the pathogen, even long after it is gone. This immunity police force protected the mice from RSV infection for weeks after they received the vaccination. Importantly, the intensity of the immune response was achieved without the addition of any extra ingredients, known as adjuvants, which are often added to vaccines to increase immune response and can be controversial.

Preliminary results from this study may lead to the development of an RSV vaccine for humans. The production of an adjuvant-free vaccine could significantly reduce the number of hospitalizations and deaths linked to RSV.

[1] Hall, C. B. et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. New England Journal of Medicine 360, 588-598, doi:10.1056/NEJMoa0804877 (2009).

[2] Talbot, H. K., Belongia, E. A., Walsh, E. E. & Schaffner, W. Respiratory Syncytial Virus in Older Adults A Hidden Annual Epidemic. Infectious Diseases in Clinical Practice 24, 295-302 (2016).

Edited by Rachel Skipper and Karna Desai