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Microbes & Immunity

MINI-REVIEW
Progress in the development of an

Advax-adjuvanted protein capsular matrix
vaccine against typhoid fever

Nikolai Petrovsky * and Kevin P. Killeen 2
1
1 Vaxine Pty Ltd, 11-13 Walkley Avenue, Warradale, South Australia, Australia
2 Matrivax Research and Development Corporation, Boston, Massachusetts, United States of
America

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-
*Corresponding author: covalently entrapped in a poly-L-lysine and CRM197 protein matrix crosslinked by
Nikolai Petrovsky glutaraldehyde. When formulated with Advax-CpG adjuvant, Typhax demonstrated
™
(nikolai.petrovsky@vaxine.net) promising results in a range of animal models including mice, rabbits, and non-human
Citation: Petrovsky N, Killeen primates in which it induces high and sustained serum anti-Vi immunoglobulin G
KP. Progress in the development and serum bactericidal activity, without any safety or reactogenicity issues. This novel
of an Advax-adjuvanted protein
capsular matrix vaccine against vaccine approach offers the potential for a low-cost, more effective, and durable
typhoid fever. Microbes & Immunity. vaccine against typhoid fever, avoiding the need for frequent booster doses.
2025;2(1):92-100.
doi: 10.36922/mi.4497
Received: August 12, 2024 Keywords: Vaccine; Typhoid; Adjuvant; Immunization; Advax
Revised: September 2, 2024
Accepted: September 3, 2024
Published Online: October 4, 2024 1. Introduction
Copyright: © 2024 Author(s). Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is transmitted
This is an Open-Access article to humans through contaminated food and water, and it remains a major cause of
distributed under the terms of the pediatric deaths in rural regions of developing countries. According to estimates,
1
Creative Commons Attribution
2
License, permitting distribution, there were 14.3 million cases of typhoid and paratyphoid fevers globally in 2017.
and reproduction in any medium, Immunocompromised people are particularly susceptible to infection with S. Typhi
provided the original work is
properly cited. and are at increased risk of developing severe disease. S. Typhi, a Gram-negative rod,
possesses several virulence factors that enable it to survive the host’s anti-bacterial
Publisher’s Note: AccScience 3
Publishing remains neutral with response, including toxins and metallophores essential for the bacterium’s survival.
regard to jurisdictional claims in
published maps and institutional Although prompt antibiotic therapy can decrease the severity, duration, complications,
affiliations. and mortality of typhoid fever, S. Typhi has acquired resistance to oral antibiotics widely

Volume 2 Issue 1 (2025) 92 doi: 10.36922/mi.4497