Improving the immunogenicity of the pneumococcal conjugate vaccine using a synthetic carbohydrate fatty acid monosulphate squalane-in-water adjuvant

Abstract

Pneumococcal conjugate vaccines (PCVs) have been highly effective in preventing invasive pneumococcal disease. However, increasing serotype coverage of PCVs led to decreasing antibody responses against individual serotypes, possibly leading to vaccine failure. It is therefore important to improve the immunogenicity of PCVs. A novel, synthetic carbohydrate fatty acid monosulphate-based adjuvant in squalane-based oil-in-water (CMS:O/W), has proven to be safe and potent for protein-based vaccines. Here, we demonstrated that administration of CMS:O/W-supplemented PCV-13 in rabbits is safe. Primary vaccination with two different PCV-doses showed that adding CMS:O/W improved the response rate against vaccine-serotypes to 100 % (6/6 animals) and increased the antibody levels against 6/13 serotypes with a full and 7/13 serotypes with a fractional (1/5th) human dose. After booster vaccination, CMS:O/W increased the antibody levels against 2/13 serotypes. Collectively, CMS:O/W represents a promising adjuvant to enhance PCV immunogenicity, potentially mitigating the risk of decreasing antibody responses associated with increased PCV valency.