Typhoid Conjugate Vaccine Efficacious in Endemic Pediatric Population

The Typhoid Vaccine Acceleration Consortium reports that a single dose of a typhoid conjugate vaccine was effective in children aged 9 months to 16 years.

Typhoid is responsible for 117,000 to 161,000 deaths annually. While the World Health Organization (WHO) recommended a typhoid conjugate vaccine in 2018, this guidance was based on protection in studies involving healthy volunteers. No efficacy studies in endemic populations had been completed at this point.

But now, the Typhoid Vaccine Acceleration Consortium is conducting a phase 3 study on the efficacy of a typhoid conjugate vaccine in Nepal and published the interim analysis in the New England Journal of Medicine.

The Typhoid Vaccine Acceleration Consortium includes investigators from the University of Oxford, the University of Maryland, and PATH. The study enrolled 20,000 children between 9 months and 16 years of age.

Children were randomly assigned 1 of 2 vaccines—typhoid conjugate vaccine or the Group A meningococcal vaccine—using 1:1 stratified block randomization. The latter vaccine group was treated as a control.

While the study will continue to follow participants for 2 years, preliminary results have been gathered via blood tests. These results showed that typhoid occurred in 38 children who received the Group A meningococcal vaccine and in 7 children who had received typhoid conjugate vaccine. All participants recovered from their illness.

Subgroups of 1000 participants in the typhoid conjugate vaccine group and 500 participants in the Group A Meningococcal vaccine group were assigned to immunogenicity analysis. A total of 1343 participants provided at least 1 sample.

The geometric mean titer for virulence immunoglobulin G antibodies at day 28 was 2038 ELISA units per milliliter in the typhoid conjugate vaccine group and 7.0 per milliliter in the meningococcal vaccine group. Seroconversion, measured as an antibody titer that more than quadrupled 28 days after vaccination, was 99.1% in the conjugate vaccine group and 2.1% in the meningococcal vaccine group.

According to the investigators, the typhoid conjugate vaccine also has several advantages in terms of deployment capability compared to previous vaccines, such as fewer necessary doses.

“This is the first study to show that a single dose of TCV [typhoid conjugate vaccine] is safe, immunogenic, and effective, which provides clear evidence that vaccination will help efforts to control this serious disease and is a strong endorsement of the WHO policy for vaccine implementation" Andrew Pollard, BSc MBBS PhD, professor of pediatric infection and immunity at Oxford University's Department of Pediatrics and an author of the study, said in a press release.

Additionally, the typhoid conjugate vaccine also has longer lasting protection and is suitable for children under 2 years of age. Because it can be used in a younger population, the vaccine could be included in routine childhood immunization programs.

The need for an effective vaccine is high, particularly with the ongoing spread of drug-resistant typhoid. In Pakistan, the ongoing typhoid outbreak is the first reported to be ceftriaxone resistant and is resistant to the majority of antibiotics used for typhoid.

"The efficacy of these results in an endemic population adds to a growing body of evidence supporting the use of [typhoid conjugate vaccine] to reduce disease and save lives in populations that lack clean water and improved sanitation," Kathleen Neuzil, MD, MPH, director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and director of the Typhoid Vaccine Acceleration Consortium, said in the press release.