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Background Acellular pertussis vaccines are better tolerated but less immunogenic than older whole cell vaccines. Novel adjuvants may be useful to enhance their immunogenicity. First-generation natural saponins are potent immuno-enhancers but are highly reactogenic. The novel semisynthetic saponin TQL1055 was evaluated for its potential to enhance the immunogenicity of a commercially available acellular pertussis vaccine as part of a National Institute of Allergy and Infectious Disease (NIAID) funded project. Methods Groups of 10 female C57BL/6J mice were immunized subcutaneously (SC) with Adacel® (containing 0.5 mcg pertussis toxin antigen) alone or in combination with QS-21 at 20 mcg/dose or TQL1055 at 50 mcg/dose on Days 0 and 28. Serum antibody titer to pertussis antigen was determined by ELISA (Alpha Diagnostics) at Days 0, 28, and 42 and geometric mean titers (GMT) in IU/mL were determined. Body weights were measured serially for 7 days after dose 1. Results At 28 days following dose 1, mice receiving TQL1055 had an anti-pertussis toxin IgG GMT of 8492, compared with 2263 in mice receiving QS-21 (p = 0.005). At Day 42, 14 days after dose 2, the GMTs increased to 18719 in the TQL1055 group and 10851 in the QS-21 group (p = 0.0653 vs TQL1055 dose 2; p = 0.6038 vs TQL1055 dose 1). Mice in the Adacel and TQL1055 groups gained weight steadily after dose 1, while mice in the QS-21 group had an average weight loss of 10% from baseline at 3 days after dose 1 (p < 0.0001). Figure 1: TQL1055 Enhances the Antibody Response to Adacel® (Commercial Acellular Pertussis Vaccine) in C57BL/6J Female Mice Figure 2: TQL1055 Shows Enhanced Tolerability (measured by decreased weight loss) Compared to QS-21 Following Subcutaneous Injection in C57BL/6J Female Mice Conclusion TQL1055 enhanced the antibody response to a commercial acellular pertussis vaccine to a greater degree than QS-21. Additionally, TQL1055 was better tolerated than QS-21, with no weight loss after vaccination. These findings suggested that TQL1055 may improve the performance of acellular pertussis vaccines without an increase in reactogenicity. Disclosures Chloe Buzz, BS, Adjuvance Technologies (Employee) Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Phil Livingston, MD, Adjuvance Technologies (Consultant, Shareholder) Eric Farris, PhD, Adjuvance Technologies (Employee) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)

Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O-glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin–conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different aberrent O-glycopeptide epitopes derived from MUC1. These autoantibodies represent a previously unaddressed source of sensitive biomarkers for early detection of cancer. The methods we have developed for chemoenzymatic synthesis of O-glycopeptides on microarrays may allow for broader mining of the entire cancer O-glycopeptidome. Cancer Res; 70(4); 1306–13