Delving into the Latest Updates on Typhax with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Typhoid fever vaccine (Vaxine), Typhoid vaccine (Matrivax), Vi PCMV

Target-

Action

stimulants

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesOther Diseases

Active Indication

Typhoid Fever

Inactive Indication-

Originator Organization

Matrivax Research & Development Corp.

Active Organization

Vaxine Pty Ltd.

Inactive Organization

Matrivax Research & Development Corp.

License Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Typhax is an investigational typhoid fever vaccine candidate that is comprised of Vi polysaccharide from Salmonella enterica serovar typhi (S. Typhi) non-covalently entrapped in a glutaraldehyde catalyzed, cross-linked α-poly-L-lysine and CRM₁₉₇ protein matrix. A previous Phase 1 trial of an aluminum phosphate adjuvanted Typhax formulation showed it induced Vi IgG after a single dose but that subsequent doses failed to further boost Vi IgG levels. The current study asked whether Advax-CpG adjuvant might instead be able to overcome polysaccharide-induced immune inhibition and improve Typhax immunogenicity. Advax-CpG adjuvanted Typhax elicited high and sustained Vi IgG responses in mice, rabbits and non-human primates (NHP) with levels being boosted by repeated immunization. High Vi antibody responses were lost in CD4 + T cell depleted mice confirming that despite the lack of conjugation of the polysaccharide to the carrier protein, Typhax nevertheless acts in a T cell dependent manner, explaining its ability to induce long-term B cell memory responses to Vi capable of being boosted. In NHP, Advax-CpG adjuvanted Typhax induced up to 100-fold higher Vi IgG levels than the commercial Typhim Vi polysaccharide vaccine. Typhax induced high and sustained serum bactericidal activity against S. Typhi and stimulated robust Vi IgG responses even in animals previously primed with a pure polysaccharide vaccine. Hence Advax-CpG adjuvanted Typhax vaccine is a highly promising candidate to provide robust and durable protection against typhoid fever.

03 Jun 2019·Human Vaccines & ImmunotherapeuticsQ3 · MEDICINE

In vitro characterization and preclinical immunogenicity of Typhax, a typhoid fever protein capsular matrix vaccine candidate

Q3 · MEDICINE

Article

Author: Thanawastien, Ann ; Mekalanos, John J. ; Killeen, Kevin P. ; Cartee, Robert T. ; Griffin, Thomas J.

Typhax is an investigational typhoid fever vaccine candidate that was GMP manufactured applying Protein Capsular Matrix Vaccine (PCMV) technology. It consists of Vi polysaccharide antigen, derived from S. Typhi, non-covalently entrapped in a glutaraldehyde catalyzed cross-linked α-poly-L-lysine and CRM197 protein matrix. Analysis of Typhax determined the average molecular weight of the vaccine particles was approximately 6 x 10⁶ Daltons, corresponding to particles containing 1-2 molecules of Vi polysaccharide and 10-20 molecules of CRM197 protein. The ratio of the concentration of Vi to CRM197 protein in Typhax is 2.4:1. Preclinical immunogenicity studies in mice demonstrated that Typhax was immunogenic and elicited a significant increase in anti-Vi IgG antibody titers following each immunization. The anti-Vi IgG antibody response elicited by Typhax in rabbits increased as the dose increased from 0.1 µg to 2.5 µg. Further, at the 2.5 and 10 µg dose levels, the anti-Vi IgG antibody titers increased after the second and third immunizations. At the 10 µg dose level, 100% of rabbits seroconverted. In the non-human primate (NHP) study, 100% seroconversion was observed at both 2.5 µg and 10 µg dose levels after the first immunization. A murine in vivo immunopotency study demonstrated that Typhax stored at 4°C was stable for at least 30 months. Collectively, the Typhax in vitro profile, preclinical immunogenicity studies, and rabbit toxicology study indicate that Typhax is a viable typhoid fever vaccine candidate for Phase 1 clinical trial evaluation.

Microbes & Immunity

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

Article

Author: Killeen, Kevin P ; Petrovsky, Nikolai

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.

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