Progress in the development of an Advax-adjuvanted protein capsular matrix vaccine against typhoid fever

Abstract

Typhoid fever, caused by Salmonella Typhi, remains a significant global public health concern, with an estimated 11 - 20 million cases annually. Vaccines are critical to controlling typhoid fever. Widespread vaccination diminishes the emergence of antibiotic-resistant strains of S. Typhi. The economic benefits of vaccination are also substantial, as the costs of treating typhoid fever and its complications can be significant. Ty21a®, a killed whole-cell vaccine, and Vivotif®, a live-attenuated vaccine, have been available for decades but have relatively short durations of action and only provide partial protection. Vi polysaccharide-conjugate vaccines have improved the durability of protection, but there is still room for improvement. Typhax™, a novel alternative to traditional conjugate vaccines, utilizes Vi polysaccharide that is non-covalently entrapped in a poly-L-lysine and CRM197 protein matrix crosslinked by glutaraldehyde. When formulated with Advax-CpG™ adjuvant, Typhax demonstrated promising results in a range of animal models including mice, rabbits, and non-human primates in which it induces high and sustained serum anti-Vi immunoglobulin G and serum bactericidal activity, without any safety or reactogenicity issues. This novel vaccine approach offers the potential for a low-cost, more effective, and durable vaccine against typhoid fever, avoiding the need for frequent booster doses.

Keywords

Vaccine / Typhoid / Adjuvant / Immunization / Advax

Funding

The writing of this paper was supported in part by the National Institutes of Health, National Institute of Allergy and Infectious Diseases, USA (grand no.: HHSN272200800039C, HHSN272201400053C, and HHSN272201800044C). The paper’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.

Conflict of interest

Nikolai Petrovsky is an affiliate of Vaxine Pty Ltd which has proprietary interests in Advax-CpG adjuvant, while Kevin P. Killeen is an affiliate of Matrivax Inc. which has proprietary interests in the Typhax vaccine.