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Microbes & Immunity Advax-adjuvanted typhoid vaccine

Figure 1. Schematic shows the differences between the traditional polysaccharide conjugation approaches where short segments of polysaccharide are
directly crosslinked to the carrier protein and the protein capsular matrix vaccine (PCMV) approach where the carrier protein is crosslinked to itself,
thereby trapping the full‑length polysaccharide chains in the crosslinked protein matrix. The PCMV antigen can then be formulated with a relevant
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adjuvant such as Advax‑CpG to further enhance vaccine immunogenicity
the polysaccharides are used. In the PCMV process, the Vi enhance vaccine potency (Table 2). To date, commercial
polysaccharide antigen purified from S. Typhi is entrapped polysaccharide-conjugate vaccines, such as Prevnar, have
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in a glutaraldehyde-catalyzed matrix of crosslinked either been used alone or with aluminum salt adjuvants.
1
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α-poly-L-lysine (α‑PLL) and CRM197 protein, a genetic Advax adjuvant (VO_0005324 ) was developed as part
toxoid of diphtheria toxin and a common carrier protein of the NIH Adjuvant Development Program. and is
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used in conjugate vaccines. The non-covalent entrapment derived from inulin polysaccharide formulated into
of polysaccharide antigens in a crosslinked matrix of protein microcrystalline particles referred to as delta inulin. 28-30
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provides the benefits of conjugated vaccines such as the Advax adjuvants have been demonstrated to enhance
ability to induce helper T cells and enhance antibody levels, immunogenicity and vaccine protection across a diversity
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without the complexity and expense of direct multi-step of viral, bacterial, and parasitic vaccines. 31-36 Advax
polysaccharide conjugation to a carrier protein. Notably, formulations can be complemented by the addition of
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PCMV was effective in inducing helper T cells for the B cell TLR9‑active CpG oligonucleotides to form a combination
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response to the polysaccharide antigen, showcasing all the adjuvant known as Advax‑CpG (VO_0005207 ) that
benefits of a conjugate vaccine. PCMV technology thereby further enhances vaccine potency. 31,32,37 CpG55.2 is a
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offers a simpler and cheaper means to manufacture the S. potent human TLR9 agonist that was the first licensed
Typhi vaccines with similar characteristics as the conjugate human drug molecule designed by artificial intelligence.
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vaccine, an important consideration given that the vast Advax adjuvants were shown to be safe and well-tolerated
majority of S. Typhi vaccines are needed in the poorest and enhance immunogenicity in human clinical trials of
developing countries where S. Typhi is endemic. Such cheap influenza, hepatitis B, and insect sting allergy vaccines 38-40
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and affordable vaccines, particularly if they provide long- and are a key component in SpikoGen vaccine, a
term durable protection, could be extremely important for recombinant protein COVID‑19 vaccine licensed for use
global S. Typhi eradication campaigns. The PCMV approach in the Middle East in adults and children aged 5 years and
has already been shown to be safe and effective in a human older, with 8 million doses having been safely delivered. 41-44
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phase 1 clinical trial of Typhax . One of the notable properties of Advax adjuvants is that
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they are highly effective in newborns where they uniquely
4. Typhoid vaccine adjuvants overcome neonatal immune hypo-responsiveness. 45-47 This
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makes the Advax family of polysaccharide adjuvants
Pure polysaccharide vaccines typically are T-cell uniquely suited for development with S. Typhi vaccines.
independent and hence unlikely to benefit from
formulation with traditional adjuvants. By contrast, 5. Advax-CpG adjuvanted Typhax vaccine
protein-conjugate vaccines are able to enlist helper T cell
responses directed at the carrier protein, with these T Immunizations of mice, rabbits, and non-human primates
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cells then able to provide help to polysaccharide-specific (NHP) with the Typhax vaccine formulated with Advax-
memory B cells to become long-lived plasma cells. The 1 https://vac.niaid.nih.gov/view?id=38
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PCMV approach allows the use of an adjuvant to further 2 https://vac.niaid.nih.gov/view?id=37

Volume 2 Issue 1 (2025) 95 doi: 10.36922/mi.4497