- 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. In vitro, human anti-Rha antibodies are shown to enhance the uptake of a model antigen, Rha-ovalbumin (Rha-Ova), by APCs. In vivo, 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 Pam3CysSK4, a Toll-like receptor (TLR) agonist linked via copper-free cycloaddition chemistry to a 20-amino-acid glycopeptide derived from the tumor marker MUC-1 containing the tumor-associated carbohydrate antigen α-N-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.
- Hossain, Md Kamal,Vartak, Abhishek,Karmakar, Partha,Sucheck, Steven J.,Wall, Katherine A.
-
-
Read Online
- SYNTHETIC LIPOPEPTIDE VACCINES AND IMMUNOTHERAPEUTICS
-
Single molecules useful in vaccine compositions, and methods of making and using the same, are described.
- -
-
Paragraph 0040; 00130-00131
(2018/04/20)
-
- Stereochemical dependence of the self-assembly of the immunoadjuvants Pam3Cys and Pam3Cys-Ser
-
The lipopeptide tripalmitoyl-S-glycerylcysteme (Pam3Cys) is derived from the N-terminal part of bacterial lipopeptides and is a polyclonal B-lymphocyte and macrophage activator. Derivatives of Pam3Cys constitute highly potent, nontoxic immunoadjuvants, and lipopeptide - antigen conjugates have found important applications as novel fully synthetic low-molecular-weight vaccines. To establish a possible correlation between molecular structure, aggregation properties, and biological activities, we have studied the self-assembly and monolayer properties of a range of Pam3Cys derivatives using transmission electron microscopy (TEM) and a Langmuir-film balance combined with a Brewster angle microscopy (BAM). It was found that the chirality of the glyceryl moiety and the additional serine unit impacted on the mode of aggregation and the monolayer properties. Correlations are discussed between these physicochemical properties and biological activities.
- Reichel, Frank,Roelofsen, Annie M.,Geurts, Hubertus P. M.,Haemaelaeinen, Taina I.,Feiters, Martinus C.,Boons, Geert-Jan
-
p. 7989 - 7997
(2007/10/03)
-