The World Health Organization (WHO) has announced the prequalification of one of the first licensed Typhoid Conjugate Vaccines (TCVs), allowing UN agencies to buy and supply the vaccine for preventative programs.
Since 2009, NIBSC scientists have worked to establish standards to support the safe introduction of TCVs into the global market. These vaccines hold great potential in the fight against typhoid as they can be used to protect children under the age of two, something that current typhoid vaccines are unable to do.
The prequalification of Bharat Biotech’s Typbar-TCV confirms the vaccine meets acceptable standards of quality, safety and potency so it can be used for immunisation programmes in low and middle-income countries.
WHO prequalification follows the recent recommendation by WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) for the use of TCVs in infants and children over 6 months of age. Since this recommendation, the UN agency, GAVI, the Vaccine Alliance approved funding of US$ 85 million to support the introduction of the vaccine.
In October, the Expert Committee on Biological Standardization of WHO endorsed 3 International Standards from NIBSC to support the continued development and testing of TCVs.
The 1st International Standard for human anti-Vi IgG serum (16/138) consists of a pool of post-immune sera from volunteers vaccinated with plain Vi-polysaccharide (Vi PS) vaccine or a TCV based on conjugated Vi PS as part of a clinical trial organised by the Oxford Vaccine Group. This standard is intended to be used as a benchmark for immunoassays such as ELISAs, used in clinical trial studies and will allow a comparison of the immunogenicity studies with different TCVs.
Two reference preparations of Vi PS (NIBSC 12/244: 1st International Standard for Vi polysaccharide of Citrobacter freundii; and NIBSC 16/126: 1st International Standard for Vi polysaccharide of S Typhi) have also been established. These standards contain a known quantity of Vi PS per ampoule to allow the quantification of polysaccharide content and support the evaluation of physicochemical methods and immuno-assays to determine the immunogenicity, safety and potency of both plain Vi PS and Vi PS conjugate vaccines.
Dr Sjoerd Rijpkema, Principal Scientist at NIBSC said:
"With the continuing and rapid development of conjugate vaccines, there’s increasing demand for appropriate tools to assure the quality, safety and potency of these vaccines. Our new WHO International Standards will support the harmonisation of assays used by manufacturers and National Control Laboratories to ensure the continued safety and quality of TCVs going forward."
The standards were established following collaborative studies supported by vaccine manufacturers, National Control Laboratories and academic research institutes. This work is supported by the WHO, the Coalition Against Typhoid and the Bill and Melinda Gates Foundation.
Typhoid is caused by infection with the bacterium Salmonella enterica serovar Typhi and currently affects around 22 million people and kills under a quarter of a million people every year.
Vaccination remains the most cost-effective approach to control Typhoid. However, the two vaccines currently recommended for use are not suitable for infants below two years of age.
TCVs contain Vi PS expressed by S. Typhi linked to another protein carrier, and are proposed to elicit strong, long-lived immune responses in both infants and children. Typbar-TCV is one of two licenced conjugate vaccines. A recent clinical trial run by scientists at the University of Oxford proposed that the vaccine to be up to 87% effective in the prevention of fever associated with bacteraemia in over 100 volunteers challenged with S. Typhi.