A recent study investigated the protective effects of a typhoid vaccine against microbes that are not the target of prevention.
Typhoid fever is an infection caused by the bacterium Salmonella Typhi (S. Typhi). This disease affects several million people every year and spreads by the ingestion of contaminated food and drinks. Typhoid fever can lead to major complications such as gastrointestinal bleeding and is fatal in 10-20% of cases if left untreated.
Antibiotic treatment helps to shorten the course of the illness and reduces the chances of complications. Vaccination is an important tool used to control typhoid fever. Ty21a is a live attenuated typhoid vaccine that prevents infection by S. Typhi.
Live attenuated vaccines work by introducing a weakened form of the germ causing disease in our body. Weakened microbes will not develop an infection while still triggering a strong response by the immune system. The response by the immune system will provide long-term immunity against the microbes causing illness. While vaccines fulfill their duties providing us protection from specific threats, they may also protect us in ways we did not anticipate.
Vaccines may reduce mortality unrelated to the prevention of target diseases
In recent years, research studies suggested that certain vaccines can reduce mortality in the population. What is surprising is that this effect seems unrelated to the prevention of the specific diseases they target. This non-specific protection seems to associate with live vaccines such as Bacille Calmette-Guerin (BCG), measles and oral polio vaccines.
How these vaccines provide non-specific protection is currently unknown. Scientists believe that other than providing immunity against target diseases, these vaccines might prevent infections from other germs as well.
Scientists investigated non-specific protection of typhoid vaccine
The typhoid vaccine Ty21a demonstrated similar properties. This vaccine helps with the regression of bladder cancer and improves the immune response against the influenza virus. A recent study looked at the specific effects of this vaccine on the human immune system. The results are published in the journal Science Advances.
The researchers recruited 30 volunteers between the age of 18 and 60 years and divided them into two groups. One group received vaccination with Ty21a while the other did not, and served as control. Collection of blood samples and cellular analysis allowed the monitoring of immune responses to vaccination. The scientist collected samples at the time of vaccination, two weeks later as well as at three and six months after vaccination.
Ty21a induces an immune response against multiple germs
Analysis of immune system cells called monocytes revealed their activation in vaccinated individuals for a period of over three months after vaccination. Normally, monocytes stay in circulation for just one day. It is possible that activation of monocytes for a prolonged time could associate with non-specific protection provided by the typhoid vaccine.
In another set of experiments, the scientists studied how immune cells responded to exposure to a variety of microbes causing disease. This analysis showed that white blood cells from vaccinated individuals initiated a response against microbes unrelated to typhoid fever by producing specific cytokines, which are messenger molecules of the immune system. The yeast Candida albicans, the bacterium Mycobacterium tuberculosis, and the influenza virus were the germs that showed the highest rates of response from cells of the immune system.
Typhoid vaccine could become part of wider vaccination programs in the future
In conclusion, this study investigated the non-specific protective effects of typhoid vaccine Ty21a. The scientists analyzed immune responses in cells from vaccinated individuals for a period of up to six months. They found that this vaccine stimulates a reaction of the immune system also against microbes that are not responsible for typhoid fever. Further studies are necessary to have a complete understanding of the immunity that this vaccine provides. However, this study suggests a use for this low-cost and well-tolerated vaccine in future prevention programs that take advantage of the non-specific immunity Ty21a provides.
Written by Raffaele Camasta, PhD
- Pennington, S. H., Ferreira, D. M., Caamaño-Gutiérrez, E., Reiné, J., Hewitt, C., Hyder-Wright, A. D., Gordon, S. B., & Gordon, M. A. (2019). Nonspecific effects of oral vaccination with live-attenuated Salmonella Typhi strain Ty21a. Science Advances, 5(2).
- Milligan, R., Paul, M., Richardson, M., & Neuberger, A. (2018). Vaccines for preventing typhoid fever. Cochrane Database of Systematic Reviews.
- Goodridge, H. S., Ahmed, S. S., Curtis, N., Kollmann, T. R., Levy, O., Netea, M. G., Pollard, A. J., Van Crevel, R., & Wilson, C. B. (2016). Harnessing the beneficial heterologous effects of vaccination. Nature Reviews Immunology, 16(6), 392-400.
- Typhoid vaccine may protect against other infections. https://www.eurekalert.org/pub_releases/2019-02/uol-tvm022519.php