Discovery Of Anti-Typhoid Gene May Lead To Improved Typhoid Vaccines

By C. Rajan, contributing writer

Researchers at the University of Melbourne have identified a gene that provides a natural resistance against typhoid fever, and persons carrying this gene variant have a nearly five-fold protection against the serious infectious disease.

In one of the largest studies of its kind, the researchers screened the genomes of hundreds of infected people and healthy controls in Vietnam and Nepal, and identified the gene variant that confers protection against typhoid. They found that the gene protects against infection by recognizing proteins from the bacteria responsible for typhoid, which helped stimulate an immune response.

The study authors say that this important finding represents one of the largest effects of the human gene on an infectious disease.

Lead author of the study, Dr. Sarah Dunstan at the University of Melbourne, said, “We screened the human genome to look for genes associated with susceptibility to or resistance from typhoid. We found that carrying a particular form of the HLA-DRB1 gene provides natural resistance against typhoid fever. This gene codes for a receptor that is important in the immune response by recognizing proteins from invading bacteria.”

Typhoid fever, also called enteric fever, is prevalent in many South Asian countries and predominantly affects children and young adults. It is caused by the bacteria, Salmonella Typhi or Salmonella Paratyphi, which is present in contaminated food or water. According to WHO estimates, typhoid is responsible for nearly 200,000 deaths a year globally, and nearly 27 million people are infected every year. Besides high fever and abdominal pain, typhoid infection can also cause complications such as bowel perforation, shock, and death.

Typhoid is increasingly becoming resistant to treatment with antibiotics. While there are some vaccines currently available for typhoid fever (sold by Sanofi and GSK), they are not completely effective, cannot be used to treat children, and do not protect against the related paratyphoid fever.

“If we can understand this natural mechanism of disease resistance, then we can use this knowledge to help develop improved vaccines for typhoid fever, but also potentially for other invasive bacterial disease,” says Dr. Dunstan.

The study was conducted as a research collaboration between the Genome Institute of Singapore and Oxford University Clinical Research Units in Vietnam and Nepal.

The research is published in the journal Nature Genetics.