Novel peptide TLR-4 agonist potentiates the effectiveness of vaccine therapies

The High Mobility Group Box Protein 1 (HMGB1) acts as an immunogenic peptide released as an endogenous danger signal from necrotic cells and immunological cells.

Although subunit vaccines promise to be less toxic, many are poorly immunogenic when administered without adjuvant. Aluminum salts (alum) are currently the only vaccine adjuvants approved by the US Food and Drug Administration for human use, and are not ideal for certain indications, as they favor a strong Th2 response and a weak or absent Th1 immune response. Furthermore, aluminum salts are often associated with severe toxicities resulting in bone mass loss, bone softening, and aluminum poisoning.

Davorka Messmer, Ph. D. and Bradley Messmer, Ph.D. – both Scientific Advisory Board members of Batu Biologics – have shown that a short peptide, named Hp91, whose sequence corresponds to an area within the endogenous molecule High Mobility Group Box (HMGB1) protein potentiates cellular immune responses to peptide antigen and cellular and humoral immune responses to protein antigen in vivo (Saenz et al Mol Immunol 57:191 2014).

The Messmers have demonstrated that Hp91 promoted the in vivo production of several immunomodulatory cytokines: IFN-γ, TNF-α, IL-6, and IL-12, as well as the antigen-specific activation of CD8+ T cells. The Hp91 peptide also has been shown to be a potent maturation stimulus for human and mouse dendritic cells.

Batu Biologics seeks to utilize this technology licensed exclusively from the University of California San Diego to optimize the efficacy of its existing products and reposition the immunostimulatory peptide in the field of translational medicine for conditions of unmet medical need.