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Microbes & Immunity Advax-adjuvanted typhoid vaccine

available in recent years. Approximately 1 – 4% of patients 3 years and 62% protection over 7 years. However, this
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chronically harbor S. Typhi in their intestinal tract and gall formulation is impractical for infants and toddlers and
bladder and act as asymptomatic carriers. With increasing is only recommended for children over 6 years of age.
antibiotic resistance and slow progress in improving water Of concern, a recent human challenge study revealed
and sanitation in many developing countries, vaccination no protective efficacy following the live-attenuated oral
against S. Typhi is the most effective means of reducing vaccine regimen with the Ty21a vaccine failing to induce
typhoid fever deaths. An episode of typhoid fever typically an increase in anti-Vi antibody levels. Pre-existing
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results in lifelong protective immunity, with both cell- anti-Vi antibody levels were seen in those study subjects
mediated and humoral immunity being elicited following who showed protection, consistent with anti-Vi antibody
infection. At present, there are three major types of playing a role in S. Typhi protection. Another downside
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vaccines commercially available for typhoid prevention: of live-attenuated vaccines is that they are associated
oral live-attenuated vaccines, parenterally administered with frequent gastrointestinal side effects due to causing
unconjugated Vi polysaccharide, and polysaccharide- an attenuated typhoid-like illness. Live vaccines are
protein conjugates (summarized in Table 1). contraindicated in those with primary or acquired
immunosuppression in whom they could cause severe
2. Live-attenuated oral vaccines typhoid disease. Being an older technology, live vaccines

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The Vivotif vaccine is an orally administered vaccine also may contain animal-derived products such as bovine
that is based on the attenuated S. Typhi Ty21a strain in collagen which are no longer contained in newer vaccine
which multiple pathogenicity-associated genes have been types.
mutated, including those mediating the production of the
Vi polysaccharide. Three doses of Ty21a administered in 2.1. Vi polysaccharide subunit vaccines
enteric-coated capsules as an every other day regimen Vi subunit vaccines (Typhim Vi , Typherix , and
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were shown in one study to confer 67% protection over Typbar ) are single-dose, intramuscularly administered
Table 1. The pros and cons of typhoid vaccine approaches

Vaccine type Brands Pros Cons
Live attenuated Vivotif oral • Relatively low cost • Requires 3 doses
Salmonella Typhi strain • Only indicated in children aged >6 years
Ty21a • Contraindicated in primary and acquired
immunodeficiency
• Cannot be given at the same time as antibiotics
• Frequent gastrointestinal side effects
• Contains bovine‑derived material
• May have weak or no efficacy
• Cannot be adjuvanted because it is a live vaccine
Pure Vi polysaccharide Typhim Vi , • High safety • Weak efficacy at ~50%
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vaccine Typherix , and • Only a single dose is required • Only indicated in infants aged >2 years of age
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Typbar ® • Short duration of protection (<2 years)
• Unable to boost response
• Cannot be adjuvanted as it is T‑cell independent
Vi polysaccharide Typbar‑TCV ™ • High safety • More expensive
conjugate vaccine • More durable protection • Protection would wane after 5 years
• Effective in children aged >3 months
• 3‑ to 6‑fold higher peak anti‑Vi responses
• Can potentially be adjuvanted
Protein capsular matrix Typhax/Advax‑CpG ™ • High safety • None
vaccine • Up to 1000‑fold higher peak anti‑Vi responses,
suggesting the possibility of long-term
protection
• Inclusion of Advax‑CpG adjuvant overcomes
polysaccharide-associated immune suppression
• Anti‑Vi antibodies able to be strongly boosted
with repeated doses
• Induces serum bactericidal antibodies
• Low cost

Volume 2 Issue 1 (2025) 93 doi: 10.36922/mi.4497