In the Journals

Typhoid conjugate vaccine 81% effective among kids in phase 3 trial

Andrew J. Pollard, FRCPCH, PhD, FMedSci
Andrew J. Pollard,

A single-dose typhoid conjugate vaccine effectively reduced typhoid in children aged 9 months to 16 years by more than 81% during a phase 3 trial in Nepal, according to results published in The New England Journal of Medicine.

“The data from this study give confidence that the new typhoid conjugate vaccine (TCV) could have a major impact on this disease and improve the health of some of the most vulnerable children in the world,” Andrew J. Pollard, FRCPCH, PhD, FMedSci, professor of pediatric infection and immunity at the University of Oxford, told Healio. “We were delighted to see such a high level of efficacy among the population who are in such desperate need, which confirms expectations from a prototype conjugate vaccine tested almost 20 years ago and recent results from testing in Oxford, United Kingdom, using the human challenge model of typhoid infection.”

The vaccine, Typbar-TCV (Bharat Biotech), offers longer lasting immunity than older vaccines with fewer doses, according to WHO, which prequalified the vaccine last December, making it accessible in areas where it is most needed.

In the phase 3, randomized, controlled trial in Lalitpur, Nepal, researchers administered the TCV to 10,005 children, and a meningococcal capsular group A conjugate vaccine (MenA; MenAfriVac, Serum Institute of India) to 10,014 children, all of whom were aged 9 months to 16 years. Typhoid was confirmed in seven children in the TCV group and 38 children in the control group, a vaccine efficacy of 81.6% (P = .001; 95% CI, 58.8-91.8), the researchers reported.

TCV study 
A typhoid candidate vaccine reduced typhoid in children by 81% in a recent study conducted in Nepal.
Source: Bill & Melinda Gates Foundation/Samantha Reinders

“Shakya and colleagues have made an important contribution to the global fight against [Salmonella enterica serotype Typhi] infection, but global health is about impact,” Florian Marks, PhD, deputy director general of epidemiology and outcomes at the International Vaccine Institute and Jerome H. Kim, MD, director general of the International Vaccine Institute, wrote in an accompanying editorial. “If further studies support and extend these results, how can a corresponding reduction in the burden of typhoid disease and death be achieved most efficiently?”

Overall, 132 serious adverse events — 61 in the TCV group and 71 in the control group — occurred within the first 6 months, with only one event identified as vaccine-related. Fever occurred in 5% of the children who received TCV and 5.4% of the children who received MenA within the first week of vaccination, and seroconversion in an immunogenicity subgroup was 99% (677 of 683 children) in the TCV group and 2% (eight of 380 children) in the MenA group.

“The data from this study lay the path to widespread acceptance and use of the vaccine wherever there is a high burden of typhoid in childhood,” Pollard said. – by Eamon Dreisbach

Disclosure: Pollard reports receiving grants from The Bill & Melinda Gates Foundation, Wellcome Trust and the NIHR Oxford Biomedical Research Center during the conduct of the study; being chair of the United Kingdom Department of Health and Social Care’s Joint Committee on Vaccination & Immunization and the European Medicine Agency scientific advisory group on vaccines; and being a member of WHO’s Strategic Advisory Group of Experts. Please see the study and editorial for all other authors’ relevant financial disclosures.

Andrew J. Pollard, FRCPCH, PhD, FMedSci
Andrew J. Pollard,

A single-dose typhoid conjugate vaccine effectively reduced typhoid in children aged 9 months to 16 years by more than 81% during a phase 3 trial in Nepal, according to results published in The New England Journal of Medicine.

“The data from this study give confidence that the new typhoid conjugate vaccine (TCV) could have a major impact on this disease and improve the health of some of the most vulnerable children in the world,” Andrew J. Pollard, FRCPCH, PhD, FMedSci, professor of pediatric infection and immunity at the University of Oxford, told Healio. “We were delighted to see such a high level of efficacy among the population who are in such desperate need, which confirms expectations from a prototype conjugate vaccine tested almost 20 years ago and recent results from testing in Oxford, United Kingdom, using the human challenge model of typhoid infection.”

The vaccine, Typbar-TCV (Bharat Biotech), offers longer lasting immunity than older vaccines with fewer doses, according to WHO, which prequalified the vaccine last December, making it accessible in areas where it is most needed.

In the phase 3, randomized, controlled trial in Lalitpur, Nepal, researchers administered the TCV to 10,005 children, and a meningococcal capsular group A conjugate vaccine (MenA; MenAfriVac, Serum Institute of India) to 10,014 children, all of whom were aged 9 months to 16 years. Typhoid was confirmed in seven children in the TCV group and 38 children in the control group, a vaccine efficacy of 81.6% (P = .001; 95% CI, 58.8-91.8), the researchers reported.

TCV study 
A typhoid candidate vaccine reduced typhoid in children by 81% in a recent study conducted in Nepal.
Source: Bill & Melinda Gates Foundation/Samantha Reinders

“Shakya and colleagues have made an important contribution to the global fight against [Salmonella enterica serotype Typhi] infection, but global health is about impact,” Florian Marks, PhD, deputy director general of epidemiology and outcomes at the International Vaccine Institute and Jerome H. Kim, MD, director general of the International Vaccine Institute, wrote in an accompanying editorial. “If further studies support and extend these results, how can a corresponding reduction in the burden of typhoid disease and death be achieved most efficiently?”

Overall, 132 serious adverse events — 61 in the TCV group and 71 in the control group — occurred within the first 6 months, with only one event identified as vaccine-related. Fever occurred in 5% of the children who received TCV and 5.4% of the children who received MenA within the first week of vaccination, and seroconversion in an immunogenicity subgroup was 99% (677 of 683 children) in the TCV group and 2% (eight of 380 children) in the MenA group.

“The data from this study lay the path to widespread acceptance and use of the vaccine wherever there is a high burden of typhoid in childhood,” Pollard said. – by Eamon Dreisbach

Disclosure: Pollard reports receiving grants from The Bill & Melinda Gates Foundation, Wellcome Trust and the NIHR Oxford Biomedical Research Center during the conduct of the study; being chair of the United Kingdom Department of Health and Social Care’s Joint Committee on Vaccination & Immunization and the European Medicine Agency scientific advisory group on vaccines; and being a member of WHO’s Strategic Advisory Group of Experts. Please see the study and editorial for all other authors’ relevant financial disclosures.