Typhoid Vaccine May Offer Extended Protections

New research shows that vaccination with the live oral typhoid vaccine Ty21a may also protect people from other types of infection. 

This is good news for the developing world, where infectious diseases are common and where broader immunization protection could potentially save more lives. 

Typhoid fever is a bacterial bloodstream infection caused by Salmonella Typhi that is estimated to affect between 11-18 million people and cause between 128,000-190,000 deaths annually, says the World Health Organization. 

The burden of typhoidal disease is highest in children under 5 years. 

In the USA, Vivotif is a Typhoid Vaccine Live Oral Ty21a authorized by the Food and Drug Administration (FDA) for immunization of adults and children greater than 6 years of age against disease caused by Salmonella typhi. 

Although Ty21a, in its currently licensed capsule formulation, is not approved for use in children, it has previously been demonstrated that, when administered in liquid suspension, Ty21a is fully immunogenic in children aged between 2 and 6 years.   

"Live-attenuated Salmonella vaccines are low-cost, well-tolerated and easily administered. These vaccines could potentially be included in global vaccination programmes, not just for their impact on Salmonella, but also for their off-target, non-specific beneficial effects," said lead author Dr. Shaun Pennington from the Liverpool School of Tropical Medicine, in a press release. 

Previous evidence has suggested that some live-attenuated vaccines, such as those for measles and polio, can stimulate the human immune system to generate a wider protective response and lower all-cause mortality. 

In order to investigate whether Salmonella vaccines might offer similar protection, the researchers vaccinated a small group, 16 healthy adults, in the UK with the Ty21a vaccine and studied its impact on their immune system over the course of six months. 

They looked at immune responses targeting Salmonella as well as those targeting a range of other pathogens. 

They demonstrated that oral vaccination with S. Typhi strain Ty21a can induce up-regulation of CD11b, CD11c, CD16, CD64, CD303, TLR-4, and TLR-5 among CD14+ monocytes for as long as 3 months. We have further demonstrated that vaccination with Ty21a alters cytokine production among various cell populations in response to stimulation with nonrelated pathogens. 

The changes they observed to levels of infection-fighting white blood cells (monocytes) and immune system messengers (cytokines) suggest that Ty21a can strengthen the immune response against subsequent, unrelated infections. 

"The next step is to observe whether these responses also occur in children in low-income settings, where their impact would be greatest," says Professor Melita Gordon, from the University of Liverpool and Malawi-Liverpool-Wellcome Trust Clinical Research Programme, who was the study's principal investigator. 

These researchers add that the ability to manipulate live-attenuated Salmonella so that they express components of other pathogens could make their findings particularly exciting for future 'vector vaccine' design.