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Microbes & Immunity Advax-adjuvanted typhoid vaccine

polysaccharide vaccines approved for use in adults and Vi‑CRM197 group (304 EU/mL) were 6 times higher than
children >2 years of age. Polysaccharide‑based vaccines in those vaccinated with Typhim Vi (52 EU/mL). 17
confer variable and short‑lived immunity. Estimates Collectively, Vi‑conjugate vaccines elicit approximately
of vaccine efficacy of around 50% have been found in 3 – 6-fold higher peak anti-Vi antibody levels than pure
areas where typhoid fever is endemic, and evidence polysaccharide vaccines and thereby provide more
of indirect protection of unvaccinated neighbors of durable protection. For example, the conjugated typhoid
vaccinees has been found. 9,10 Immunity wanes within vaccine manufactured in India is said to provide 5 years of
2-year post-vaccination and there is no evidence that protection when used in typhoid-endemic regions. It may
protective efficacy lasts beyond 3 years. Re‑vaccination be able to achieve this duration of protection because, in
every 2 years is recommended for U.S. travelers to endemic regions, periodic re-exposure to S. Typhi provides
S. Typhi endemic areas. Thus, the widely available regular boosting to Vi antibody levels, thereby helping
Vi polysaccharide subunit vaccines confer relatively maintain titers above protective levels for an extended
short-term protection against typhoid in older children timeframe. Travelers from countries where typhoid is not
and adults and are poorly immunogenic in infants endemic would not get the benefit of such periodic endemic
under 2 years of age due to their inability to elicit a re-boosting, meaning that conjugate vaccines may provide
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T-cell-dependent immune response. This limits the a much shorter duration of protection to those living
utility of the pure polysaccharide vaccines for S. Typhi outside of endemic areas. Hence, there remains a need to
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eradication campaigns. create more potent and durable typhoid vaccines.
2.2. Vi polysaccharide-conjugate vaccines
3. Potential next-generation typhoid
Vi polysaccharide-conjugate vaccines in which the vaccine approaches
Vi polysaccharide is covalently coupled to a protein
antigen have recently been developed and shown to Even with the recent advent of the conjugate vaccines, the
be highly effective in children as young as 3 months of unmet need for more effective and durable typhoid vaccines
age. Immunization with a 25 µg dose of a Vi-conjugate remains. How might this be achieved? One area might be
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vaccine using CRM197 as a carrier protein developed to explore modified polysaccharide antigens better able
by the Novartis Vaccine Institute for Global Health to present key neutralizing epitopes so as to maximally
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28 days achieved anti‑Vi geometric mean titer (GMT) stimulate memory B cell responses. Consideration could
of 304 EU/mL. Bharat Biotech’s Vi‑conjugate vaccine be given to including additional antigens, such as S. Typhi
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(Typbar‑TCV ), when administered to human children lipopolysaccharide (LPS) antigens, in the vaccine. The
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at a 25 µg dose, achieved anti‑Vi GMTs approximately antigens could be formulated with newer, more potent
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3-fold higher than those obtained with their equivalent adjuvants. Finally, vaccine delivery approaches to better
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unconjugated polysaccharide vaccine (Typbar ). Two stimulate mucosal immunity could be attempted. While
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years after vaccination, anti‑Vi titers in those receiving the mRNA approaches have been touted as a way forward for
conjugate vaccine remained almost 2‑fold higher (GMT many other traditional vaccines, these can only encode
82) than in those that received the polysaccharide vaccine protein antigens and hence are not currently an option
(GMT 46). The International Vaccine Institute reported a to replace vaccines where non-protein antigens such as
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phase 2 study of a diphtheria toxoid-conjugated Vi vaccine polysaccharides are involved. Similarly, while viral-like
in children aged 6 – 24 months which achieved anti-Vi particles could theoretically be used as the protein carrier
GMT of 444.38 EU/mL. In Vietnam, Vi polysaccharide on which to conjugate polysaccharide antigens, little work
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conjugated with recombinant Pseudomonas aeruginosa has been done in this area, presumably due to the additional
exotoxin A conferred >90% protection against typhoid complexity of conjugating polysaccharides to the particles
over the first 27 months and >80% over 46 months. From as opposed to conjugating them to soluble proteins.
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this study, it was estimated that the protective level of An example of an alternative to traditional
anti‑Vi immunoglobulin G (IgG) is 3.5 EU/mL. A phase polysaccharide-conjugate approaches is the protein
1 study of the Vi-diphtheria toxoid conjugate (Vi-DT) capsular matrix vaccine (PCMV) approach. The PCMV
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conducted in the Philippines enrolled subjects aged 2 – process non-covalently entraps polysaccharide antigens
45 years who received either Vi-DT or Typhim Vi vaccine. in a crosslinked protein matrix (depicted in Figure 1A).
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The conjugated Vi-DT vaccine generated a 4-fold higher The PCMV process is simpler and cheaper than the
Vi GMT compared to the pure polysaccharide Typhim manufacture of polysaccharide-conjugate vaccines and
Vi vaccine. Similarly, in a phase 1 study in European allows full-length bacterial polysaccharides to be used,
adults, anti‑Vi GMT levels 4‑week post‑vaccination in the whereas in conjugate vaccines typically only short pieces of

Volume 2 Issue 1 (2025) 94 doi: 10.36922/mi.4497