New study confirms typhoid vaccine safety, immune response in children

The newly published research is a double-blind, randomised, controlled clinical trial done in Blantyre, Malawi

A new study, published in The Lancet Global Health, finds the typhoid conjugate vaccine, Typbar TCV, provides immunity for up to three years in children as young as nine months old in Malawi. The research was conducted by the Blantyre Malaria Project, Malawi-Liverpool-Wellcome Trust, and researchers at the Center for Vaccine Development and Global Health (CVD) at the University of Maryland School of Medicine (UMSOM) – found that the TCV vaccine is safe and well tolerated. Importantly, the vaccine can be given to nine-month-old infants at the same time as routine measles-rubella vaccinations without reducing the immune response to either vaccine.

The newly published research is a double-blind, randomised, controlled clinical trial done in Blantyre, Malawi. The study team randomly assigned 631 children with no immunosuppression or chronic health conditions to either receive the TCV typhoid vaccine or a vaccine for meningococcal serogroup A conjugate, which is routinely used in Africa. The typhoid vaccine showed strong immune responses against typhoid in children ages nine months to 12 years old.

“It is simply amazing that a single dose of TCV will protect Malawian children for years,” said Ngina Nampota, MBBS, MS, lead author of the new research and Study Physician with the Blantyre Malaria Project, an affiliate of Kamuzu University of Health Sciences, Malawi.

The new study is supported by TyVAC – a partnership between CVD, the Oxford Vaccine Group at the University of Oxford, and the global non-profit PATH. TyVAC aims to accelerate the introduction of the TCV vaccine as part of an integrated approach to reduce the burden of typhoid in countries eligible for support from Gavi, the Vaccine Alliance. TyVAC was initiated in 2016 as a multi-country project to accelerate the introduction of the TCV vaccine in Gavi-eligible countries.

“TCVs are the first vaccines that protect children as young as six months of age against typhoid. This study is one of the first to demonstrate a long-lasting immune response in African children who are disproportionately affected by typhoid and its potential consequences, including death,” said Matthew B Laurens, MD, MPH, Professor of Pediatrics and Medicine at UMSOM and senior author of the new research. “TCVs will ensure children in affected areas can lead healthier, productive lives free of typhoid.”

These vaccines offer an easy – and World Health Organization-approved – way to control this devastating disease and save lives. Data from a phase 3 clinical trial in Malawi, published in September 2021 in The New England Journal of Medicine, also showed that this vaccine is a safe and effective way to protect children under age 15, the population most affected by typhoid. The new Lancet Global Health research is a “substudy” of this larger clinical trial.

Additionally, the new study showed that children under one year of age had both a strong immune response and no significant side effects when TCV was given alongside a routine measles-rubella vaccine. In countries with limited access to health care and transportation, the ability to administer multiple vaccines in one visit improves access to preventive care. Children who receive TCV typically experience mild side effects, most commonly injection-site pain. These reactions are consistent with other similar vaccines.

“TCVs provide a ray of hope in resource-limited settings, where children are disproportionately impacted by typhoid,” said Kathleen Neuzil, MD, MPH, the Myron M Levine, MD, DTPH, Professor in Vaccinology at UMSOM and coauthor of the current study. “With the broad use of TCVs, combined with improved water and sanitation, we can make typhoid a disease of the past.” Dr Neuzil is also the director of CVD at UMSOM and principal investigator for TyVAC.

The next steps, Dr Laurens said, are to assess the effect of a booster dose on long-term protection from typhoid fever in children. While researchers continue to monitor the children vaccinated as part of this study, previous research suggests that TCV protection likely lasts at least five years.

“Our team’s goal to protect children against typhoid represents a long-term aim of scientists working across the globe,” said Mark T Gladwin, MD, Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean at UMSOM. “We are proud of these life-saving accomplishments of scientists in the University of Maryland’s Center for Vaccine Development and Global Health, who are focused on global efforts to reduce health care disparities.”

The Bill & Melinda Gates Foundation partially funded this study with grant OPP1151153. Typbar TCV is licensed by Bharat Biotech International Limited, Hyderabad, India.