In order to obtain an effective cellular and humoral immune response, a vaccine construct has to be captured, processed and presented by antigen presenting cells (APCs) through their major histocompatibility complex (MHC) molecules. Poor uptake and presentation is correlated with weak immunogenicity. One effective way to enhance antigen presentation is through an antibody-dependent antigen uptake mechanism by targeting FcγR receptors of APCs that can bind with the Fc portion of an immune complexed antibody. Anti-Rhamnose (Anti-Rha) antibody is among the most common natural anti-carbohydrate antibodies present in human serum. Therefore, rhamnose can be utilized as a targeting moiety for a rhamnose-containing vaccine to prepare an effective vaccine formulation. Binding rhamnose of a rhamnose-containing vaccine with murine anti-Rha antibody has previously been proven effective for capturing and processing of antigen by APCs via stimulatory Fc receptors. We show that human anti-Rha antibodies enhance the uptake of rhamnose-containing antigen by murine APCs in vitro. In-vivo, passive transfer of human anti-Rha antibodies into mice improves the priming of T cells to Rha-antigen. We synthesized and tested an anti-cancer vaccine containing a lipoglycopeptide cancer antigen in a Rha-bearing liposome and demonstrated improved immunogenicity. Also, we showed that direct conjugation of the Fc domain of an antibody (mouse IgG3Fc) to a liposomal vaccine instead of rhamnose can be a good approach for efficient uptake and presentation, as we can bypass the need for anti-Rha antibodies. A liposomal vaccine bearing IgG3Fc has been found to be equally effective as the Rha-vaccine at priming CD4+ T cells. Priming of CD8+ T cells for IFN-γ release and tumor cytotoxicity was promising in comparison to anti-Rha antibody targeting.

Augmenting vaccine immunogenicity through the use of natural human anti-Rha antibodies and monoclonal Fc domains

255th National Meeting (2018)

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