Streptococcus pneumoniae represents a significant cause of global morbidity and mortality in both children and adults. While there are vaccines currently available that can convey immunity to some of the major serotypes of S. pneumoniae, limited access to vaccines in low-income countries leads to insufficient coverage of those populations, and the shifting prevalence of serotypes coupled with bacterial resistance to antibiotics is a serious development in the US and Europe. The rational design

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... f semi-synthetic glycoconjugate vaccines represents a novel method for effective and economical vaccine production, and is therefore a viable strategy for addressing these problems. A new oligosaccharide-conjugate vaccine against S. pneumoniae serotype 3 (SP3), produced by glycan synthesis developed by the working group of Prof. Dr. Peter H. Seeberger (Max Planck Institute für Kolloid- und Grenzflächenforschung, MPIKG) has shown promise as one being able to induce serological responses. Here, we tested the ability of this vaccine candidate to confer immunity in a mouse model of S. pneumoniae infection. Methods: In the current study, we conducted pre-clinical in-vitro and in-vivo experiments, in accordance with WHO-guidelines for the assessment of novel vaccines, to examine the relative efficacy and safety of a novel, semi-synthetic glycoconjugate vaccine for S. pneumoniae serotype 3 (SP3). In vitro experiments encompassed opsonophagocytosis assays implementing either differentiated HL-60 cells or peripheral human neutrophils. In vivo experiments employed a mouse-model of pneumococcal pneumonia to assess vaccine protection, based on clinical parameters, bacterial clearance from the lungs, bacteremia, local and systemic cellular immune-responses to SP3 challenge, pulmonary function tests, and pulmonary endothelium barrier integrity. Results: The vaccine candidate showed a robust protective effect in mice challenged with SP3 35 days following vaccination, but waning effect with no significant protection after 116 days, indica [...]