Alum-Binding Peptides for Prolonging Antigen Exposure and Augmenting Antigen-Specific Immune Responses

Technology

Alum is a commonly used adjuvant known to increase the immune response to a vaccine. This technology is a peptide that contains phosphoserine repeats, which bind alum, and a maleimide functional group that can be reacted with protein antigens at cysteine residues to facilitate a stable interaction between the protein antigen and alum. Standard vaccine compositions are only loosely absorbed to the alum surface, and the antigen diffuses away from the alum at the injection site within 2-3 days. This conjugating technology increases the stability of the alum-antigen interaction in serum, and leads to stable alum-antigen association for two weeks in an in vivo mouse model. Importantly, the increased retention of the antigen with alum leads to increased antibody titers against the protein antigen, and in a mouse model the inventors demonstrate 10-fold higher antibody titer in comparison to standard alum compositions. Additionally, the orientation of the protein antigen adsorption to alum can be precisely controlled to focus the immune response to particular protein motifs.

Problem Addressed

In the United States, children commonly receive at least 10 recommended immunizations, most of which also require two to four booster dosages. The requirement for boosters both increases healthcare costs and decreases patient compliance due to the need for repeated return visits. Technologies that enhance the immune response from a single dosage could help to solve the issues associated multi-dose immunizations. These inventors have engineered a peptide that enhances immune responses in vaccines by conjugating protein antigens directly to alum adjuvants.

Advantages

• Simple incorporation with already established vaccine formulations
• Enhanced antigen retention
• Improved immune response with 10x higher antibody titer
• Control of protein antigen orientation