Bharat Biotech’s typhoid conjugate vaccine shows nearly 82% efficacy at 12 months in a Phase-3 trail carried out in Nepal. It can be be given to babies as young as six months. Currently available typhoid vaccines have 60-70% efficacy and cannot be given to children younger than two years.
A typhoid vaccine (Typbar TCV) developed by the Hyderabad-based Bharat Biotech has shown 81.6% efficacy in preventing typhoid fever at 12 months in a Phase-III clinical trial. The trial was carried out in Nepal in over 10,000 children who received the vaccine.
A single does of the vaccine was found to be effective in preventing typhoid in children aged nine months to 16 years. The vaccine confers protection two-three weeks after vaccination. The duration of protection is currently not known. The results of the trial were published in The New England Journal of Medicine (NEJM).
The Typbar TCV vaccine was recommended by WHO’s Strategic Advisory Group of Experts on Immunization (WHO-SAGE) in December 2017. The WHO prequalified the vaccine in January 2018.
Typhoid fever is caused by highly contagious Salmonella Typhi bacteria. Nearly 11 million fall sick due to typhoid and about 1,17,000 deaths are reported each year. The bacteria spread through contaminated food and water.
The Typbar TCV typhoid vaccine tested in Nepal is a conjugate vaccine. A conjugate vaccine is one in which the antigen (which is a polysaccharide in this case) is chemically linked to a carrier protein.
Issues with other vaccines
Two other typhoid vaccines — polysaccharide typhoid vaccine and live, weakened typhoid vaccine — are already used commercially. But the efficacy of these vaccines to protect against typhoid is lower than the conjugate vaccine that has now been tested in Nepal.
“The other two vaccines offer 60-70% protection unlike the conjugate vaccine which confers nearly 82% protection. Two doses of live, weakened typhoid vaccine are needed to reach 60-70% protection,” says Dr. V. Krishna Mohan, Executive Director at Bharat Biotech. “More importantly, the conjugate vaccine can be given to babies as young as six months, while the other two vaccines cannot be given to children below two years of age.” According to SAGE, in high-incidence settings, a large proportion of severe typhoid fever cases occur in children aged below two years.
While typhoid bacteria can be treated with antibiotics, the microbes have developed resistance against multiple antibiotics. Multi-drug resistant typhoid bacteria are seen in south Asia including India. Since 2016, extensively drug-resistant (XDR) typhoid outbreaks have been reported from Sindh province in Pakistan. According to an Editorial accompanying the paper, XDR typhoid has been found in India, Bangladesh, and Pakistan.
Earlier, a small phase-3 trial carried out in India by Bharat Biotech and University of Maryland School of Medicine, Baltimore in two groups — 2-45 years old and 6-23 months old — found that a single dose of the vaccine was able to provoke immune response in 98% of the vaccinated children. The results were published in the journal Clinical Infectious Diseases.
A phase-2b human challenge trial was carried out in adult healthy volunteers aged 18-60 years who are typhoid naïve (no history of typhoid infection or vaccination). The volunteers were first vaccinated and then exposed to the bacteria to assess the ability of the vaccine to prevent infection. The results published in December 2017 in the Lancet showed that the vaccine has 88% efficacy in preventing an infection.
Exporting to Pakistan
The vaccine has already been licensed in India and is available for clinical use. Bharat Biotech has been supplying the typhoid conjugate vaccine to Pakistan since 2017. “So far about 10 million vaccines have been supplied to Pakistan,” says Dr. Mohan. Pakistan is the first country to introduce the typhoid conjugate vaccine as part of its national immunisation programme.