Authors: Lucille F. van Beek a, Christa van der Gaast-de Jongh a, Peter Paul Platenburg b, Luuk Hilgers b, Marien I. de Jonge a
aLaboratory of Medical Immunology, Radboud University Medical Center, Radboudumc Community for Infectious Diseases, Nijmegen, Geert Grooteplein Zuid 10, 6525, GA, the Netherlands
bLiteVax BV, Ophemert, Akkersestraat 50, 4061, BJ, the Netherlands
Vaccine – Volume 51, 2 April 2025, 126893
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.
1. Introduction
Streptococcus pneumoniae infections are an important cause of morbidity and mortality globally. Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease (IPD) in a serotype-specific manner. Replacement of vaccine-serotypes by non-vaccine-serotypes causing pneumococcal infections limits the efficacy of PCVs, stresses the need for vaccines with broader coverage and led to the expansion of PCV valency from 7 to 24 serotypes [1]. However, data on reduced antibody responses against individual serotypes associated with increased PCV valency is accumulating [2,3], potentially resulting in sub-optimal antibody levels and break-through infections [3]. Enhancing PCV immunogenicity using adjuvants with higher potency than alum salts are therefore of interest [4].
Adding an adjuvant to PCVs has proven to enhance immunogenicity in several pre-clinical studies [[5], [6], [7]]. In humans, supplementation of PCV-9 with monophosphoryl lipid A did not improve the antibody response [8], while PCV-7 supplementation with synthetic oligodeoxynucleotide-containing CpG motifs did, however this induced higher reactogenicity [9,10].
A novel synthetic carbohydrate fatty acid monosulphate ester (CMS)-based adjuvant formulated in a squalane-based oil-in-water (O/W) emulsion (CMS:O/W) is extreme stable, and has shown to be a safe and potent adjuvant in combination with protein antigens [[11], [12], [13], [14]]. Moreover, CMS:O/W is under clinical evaluation in combination with an influenza vaccine (NCT05581407; NCT06294262), opening opportunities for clinical evaluation of CMS:O/W combined with other vaccines [15]. Here, we investigated the safety and immunogenicity of CMS:O/W-adjuvanted PCV-13 in rabbits.
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