Q11: a Highly Homogeneous Multivalent and Single-component Vaccine Adjuvating Platform

SUMMARY

• There is a limited choice in clinically approved adjuvants for vaccine development. Current solutions are themselves immunogenic, causing injection site swelling and reactions.
• The inventors developed a 15 amino acid peptide adjuvant (Q11) that forms a highly homogeneous network of laterally assembled beta sheet fivers in aqueous solution. When tested in the absence of vaccine antigen, Q11 does not elicit an immune response.
• The invention is a novel peptide-based vaccine adjuvant platform where the antigen is conjugated to Q11, forming a single-component antigen-adjuvant vaccine. The vaccine self-assembles into fibril networks that are highly thermostable, homogeneous, and can display antigen multivalently on the surface with controlled dosing in a manner that provokes a strong B Cell response. The vaccine can also be doped with PADRE, a T cell helper antigen to further boost immune recognition.
• In in vivo proof of concept experiments, C57BL/6 mice were immunized with either the antigen alone (OVA or ESAT-6) or Q11-conjugated antigens (Q11+OVA or Q11+ESAT-6). The antigens alone did not elicit an immune response, but the Q11-conjugated antigens elicited a strong B-Cell dependent IgG response.

FIGURE

Self-assembled Q11 fused to M. tuberculosis antigen, ESAT (ESAT-Q11), produced robust IgG antibody titers compared to unadjuvanted ESAT (pink). ESAT-Q11 vaccine peptides heated to 45C (red, blue) maintained efficacy, demonstrating the vaccine’s thermostability. Mice were boosted on day 10.

ADVANTAGES

ADVANTAGES

• Dosing precision for T- and B-Cell stimulation
• Reduced injection site inflammation without diminishing efficacy
• Highly thermostable which extends shelf life
• Controlled and uniform fibril formation prior to administration
• Multiple antigens can be combined in a single dose

APPLICATIONS

• Single-dose, multi-component vaccine development
• Vaccine development for difficult and non-immunogenic antigens

PUBLICATIONS

• Sun, T; et al. Thermal stability of self-assembled peptide vaccine materials. Acta Biomater. 2016 Jan 15;30: 62-71.
• Rudra, JS; et al. A self-assembinlg peptide acting as an immune adjuvant. Proc Natl Acad Sci U S A. 2010 Jan 12; 107(2):622-7.

• US: 9,241,987
• US: 9,849,174

• In Vivo preclinical with two antigens: OVA antigen (Chick Ovalbumin) ESAT6 Antigen (Tuberculosis)
• Head to head comparison with alum and CFA