1 research outputs found
Augmenting Vaccine Immunogenicity through the Use of Natural Human Anti-rhamnose Antibodies
Utilizing
natural antibodies to augment vaccine immunogenicity
is a promising approach toward cancer immunotherapy. Anti-rhamnose
(anti-Rha) antibodies are some of 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. It was shown previously that anti-Rha
antibody generated in mice binds effectively with Rha-conjugated vaccine
and is picked up by antigen presenting cells (APCs) through stimulatory
Fc receptors. This leads to the effective uptake and processing of
antigen and eventually presentation by major histocompatibility complex
(MHC) molecules. In this article, we show that natural human anti-Rha
antibodies can also be used in a similar mechanism and immunogenicity
can be enhanced by targeting Rha-conjugated antigens. In doing so,
we have purified human anti-Rha antibodies from human serum using
a rhamnose affinity column. <i>In vitro</i>, human anti-Rha
antibodies are shown to enhance the uptake of a model antigen, Rha-ovalbumin
(Rha-Ova), by APCs. <i>In vivo</i>, they improved the priming
of CD4+ T cells to Rha-Ova in comparison to non-anti-Rha human antibodies.
Additionally, increased priming of both CD4+ and CD8+ T cells toward
the cancer antigen MUC1-Tn was observed in mice that received human
anti-Rha antibodies prior to vaccination with a rhamnose-modified
MUC1-Tn cancer vaccine. The vaccine conjugate contained Pam<sub>3</sub>CysSK<sub>4</sub>, a Toll-like receptor (TLR) agonist linked <i>via</i> copper-free cycloaddition chemistry to a 20-amino-acid
glycopeptide derived from the tumor marker MUC-1 containing the tumor-associated
carbohydrate antigen α-<i>N</i>-acetyl galactosamine
(GalNAc). The primed CD8+ T cells released IFN-γ and killed
tumor cells. Therefore, we have confirmed that human anti-Rha antibodies
can be effectively utilized as a targeting moiety for making an effective
vaccine