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Review
. 2023 May 16:10:1201693.
doi: 10.3389/fmolb.2023.1201693. eCollection 2023.

Exploring the variables influencing the immune response of traditional and innovative glycoconjugate vaccines

Francesca Micoli  1 , Giuseppe Stefanetti  2 , Calman A MacLennan  3   4   5
Affiliations
Review

Exploring the variables influencing the immune response of traditional and innovative glycoconjugate vaccines

Francesca Micoli et al. Front Mol Biosci. .

Abstract

Vaccines are cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The rapid evolution of pneumococcal conjugate vaccines, the introduction of tetravalent meningococcal conjugate vaccines, mass vaccination campaigns in Africa with a meningococcal A conjugate vaccine, and the recent licensure and introduction of glycoconjugates against S. Typhi underlie the continued importance of research on glycoconjugate vaccines. More innovative ways to produce carbohydrate-based vaccines have been developed over the years, including bioconjugation, Outer Membrane Vesicles (OMV) and the Multiple antigen-presenting system (MAPS). Several variables in the design of these vaccines can affect the induced immune responses. We review immunogenicity studies comparing conjugate vaccines that differ in design variables, such as saccharide chain length and conjugation chemistry, as well as carrier protein and saccharide to protein ratio. We evaluate how a better understanding of the effects of these different parameters is key to designing improved glycoconjugate vaccines.

Keywords: carbohydrate; conjugation variables; glycoconjugate; immune response; vaccines.

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Conflict of interest statement

FM is employee of the GSK group of companies and owner of GSK shares. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) The two main approaches to traditional conjugation of saccharides to proteins (linkers are not always present) and main variables impacting immunogenicity; (B) Innovative carbohydrate based vaccines based on bioconjugation, dmOMV and MAPS technologies.
FIGURE 2
FIGURE 2
Two main approaches of conjugation: (A) random linkage sites along the PS or OS chain, resulting in high molecular weight cross-linked and rather undefined and heterogeneous conjugate structures and (B) selective attachment at the terminal end of the OS, resulting in better-defined conjugates without chemical modification of the saccharide chain. (A1–A2) Some commonly used methods for random activation of the PS using OH groups (1) or COOH groups (2) along the saccharide chain. (B1) An example of selective conjugation after depolymerization of the PS by mild acid hydrolysis. Mild hydrolysis, for example, of MenA PS, generates one terminal aldehyde group per shorter saccharide chain. Resulting aldehyde groups are linked to the protein or to the spacer by reductive amination.
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