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Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine.
Staphylococcus aureus(S. aureus) is a pathobiont of humans as well as a multitude of animalspecies. The high prevalence of multi-resistant and more virulent strains ofS. aureusnecessitatesthe development of new prevention and treatment strategies forS. aureusinfection. Major advancestowards understanding the pathogenesis ofS. aureusdiseases have been made using conventionalmouse models, i.e., by infecting naïve laboratory mice with human-adaptedS. aureusstrains. However,the failure to transfer certain results obtained in these murine systems to humans highlights thelimitations of such models. Indeed, numerousS. aureusvaccine candidates showed promising resultsin conventional mouse models but failed to offer protection in human clinical trials. These limitationsarise not only from the widely discussed physiological differences between mice and humans, but alsofrom the lack of attention that is paid to the specific interactions ofS. aureuswith its respectivehost. For instance, animal-derivedS. aureuslineages show a high degree of host tropism and carry arepertoire of host-specific virulence and immune evasion factors. Mouse-adaptedS. aureusstrains,humanized mice, and microbiome-optimized mice are promising approaches to overcome theselimitations and could improve transferability of animal experiments to human trials in the future.