Vaccination for yellow fever – a new way of reducing breast cancer risk?

New research has unveiled that breast cancers produce proteins very similar to those made by the virus that causes yellow fever. Since vaccines have been created to prevent yellow fever, there is a potential that the vaccine could also be used to prevent breast cancer.

Scientists have been trying to find ways to develop vaccines to target potential cancer cells for years. However, only a handful have been successfully implemented, such as the vaccine for human papillomavirus (HPV), which helps prevent HPV infections that cause cervical and head and neck cancers1. Few other cancer types are caused by viruses, making them difficult to target with vaccines2.

How do vaccines work?

Vaccines introduce a small amount of a virus into your system – not enough to cause symptoms, but enough to make your immune cells familiar with foreign particles3. In response, the body develops an army of immune cells that are specifically designed to target that virus. After immunization, the presence of any viral particles in the body will lead to the mobilization of the targeted immune cell army and destruction of the virus before infection sets in3.

Yellow fever vaccine may prevent breast cancer

A study published in the European Journal of Cancer Prevention showed that the yellow fever vaccine may be linked to a decrease in breast cancer risk in women aged 40-544. Researchers in Veneto, Italy looked back at medical records of women who received the yellow fever vaccine and looked for breast cancer diagnoses after vaccination. Among 12,804 women who received the vaccination, 187 cases of breast cancer were found. Women who received the vaccine between the ages of 40 and 54 experienced the greatest decrease in breast cancer risk with a 54% reduction in breast cancer incidence following administration of the yellow fever vaccine4. The researchers therefore proposed that the vaccine could help protect against breast cancer.

Retroviruses in breast cancer

Breast cancer itself has not been linked to viral infection. However, breast cancers produce human endogenous retroviral (HERV) proteins that closely resemble the proteins produced by yellow fever. Other cancers including melanoma, ovarian cancer, and prostate cancer have also been shown to express these HERV proteins5. HERVs are remnants of ancestral infections that have become incorporated in our DNA and passed down through several generations.  They have been maintained as part of our cells because they serve some function that is beneficial to human physiology. Approximately 8% of our DNA can be traced back to HERVs5.

Using the yellow fever vaccine to target breast cancer

The yellow fever vaccine was first developed in 1937 to target the yellow fever virus, which causes liver dysfunction and yellowing of the skin (hence the term yellow fever)3. When vaccinated, the body develops an army of immune cells called T cells to target the yellow fever virus. Because of the similarities between yellow fever and the HERVs produced in breast cancer, the army of T cells will also recognize and destroy any HERV-producing breast cancer cells3.  Think of it in terms of languages. The T cells have been trained to understand English, a language that is spoken by both the yellow fever virus (with an American accent) and the breast cancer HERVs (with an Australian accent). Regardless of the accent, the T cells will still be able to recognize and understand both types of proteins. This is called “cross-reactivity”. However, if the T cells meet another type of virus speaking a different language, for example HPV speaking French, the T cells will not be able to understand or act on the signals from that virus.

Next steps

While the findings in this study are interesting, a vaccine for breast cancer is still far from reality. More active studies are necessary in order to establish the relationship between breast cancer and the vaccine for yellow fever as well as to determine the mechanism by which this vaccine affects breast cancer risk. This could be in the form of a clinical trial, with some women receiving the vaccine and others receiving a placebo4. If the relationship is real, it would be very easy to implement this vaccine because it is already mass-produced and has been administered more than 540 million times4. This finding is therefore an exciting step forward in the world of cancer vaccines.

References 

  1. Psyrri, A. & DiMaio, D. Human papillomavirus in cervical and head-and-neck cancer. Nat. Clin. Pract. Oncol. 5, 24–31 (2008).
  2. Tabi, Z. & Man, S. Challenges for cancer vaccine development. Advanced Drug Delivery Reviews 58, 902–915 (2006).
  3. Barrett, A. D. & Teuwen, D. E. Yellow fever vaccine – how does it work and why do rare cases of serious adverse events take place? Current Opinion in Immunology 21, 308–313 (2009).
  4. Mastrangelo, G., Pavanello, S., Fadda, E., Buja, A. & Fedeli, U. Yellow fever vaccine 17D administered to healthy women aged between 40 and 54 years halves breast cancer risk. Eur. J. Cancer Prev. 1 (2016).
  5. Downey, R. F. et al. Human endogenous retrovirus K and cancer: Innocent bystander or tumorigenic accomplice? Int. J. Cancer 137, 1249–1257 (2015).

This article was written by Catherine Crawford-Brown, a M.Sc candidate in the Department of Pathology and Molecular Medicine, and part of the Collaborative Graduate Program in Cancer Research at Queen’s University.