Multivalent Immunogen Displays

When compared to subunit vaccines or antigen presentation by mRNA vaccines, multi-immunogen displays are capable of producing superior immune responses due to the following:

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• Greater complement activation - Nanoparticle surfaces displaying free amino groups are more amenable to activation of the complement cascade, via enhanced C3b binding [15] and increased complement-associated removal [16, 17] associated with multiple nanoparticle systems. [18, 19]

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• Highly repetitive surfaces - Repetitive immunogen patterns on the nanoparticle surface typically constitute a pathogen-associated pattern,[20] allowing higher avidity interactions with repetitive surfaces.  This is important as, in the case of IgM, the interaction itself is of low affinity and allows for nanoparticles to induce complement activation cascades more readily than simple subunit vaccines.[21]

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• Optimal distance between antigens - IgG is a bivalent molecule possessing identical Fab arms spaced 15 nm apart.  This bifurcated structure allows IgG to crosslink to soluble antigens and recognize repetitive epitopes, thus increasing binding avidity.  Most viruses present extremely dense surface antigen arrays resulting in an optimal peptide of 10–15 nm on the liposome surface. Nanoparticles mimic this spacing.[22]

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• Enhanced dendritic cell processing – Dendritic cells are the single most important antigen presenting cell in the body. Enhanced phagocytosis by dendritic cells enhances humoral and cellular responses. Multi-immunogen displays are immunologically more effective than microparticles [23] or soluble immunogens.[24]  Dendritic cells entering the lymph nodes present processed nanoparticle-derived peptides to CD4+ T cells, which ultimately helps activate B cells.  This results in higher class switching and longer-lived antibodies.  Without T cell help, B cell responses are short-lived and less effective.

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• Greater ability to form cross-reactive antibodies - Multivalent immunogen displays constructed using multiple different epitopes of similar immunogenic proteins have been shown to result in the production of broad, cross-reactive antibodies resulting in neutralizing antibody populations that are effective against a range of similar epitopes that are NOT contained in the original vaccine formulation. [10, 13] 

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Multivalent immunogen displays can give rise to antibodies that recognize commonalities between conserved molecular surfaces with the ability to neutralize ANY immunogenic protein possessing the conserved region.[14, 25]