Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

Abstract

Streptococcus pneumoniae infections lead to high morbidity and mortality rates worldwide. Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but have a limited range of protection, which encourages the development of a broadly protective protein-based alternative. We and others have shown that immunization with pneumococcal lipoproteins that lack the lipid anchor protects against colonization. Since immunity against S. pneumoniae is mediated through Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects of a lipid modification on the induced immune responses in either intranasally or subcutaneously vaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrA strongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhanced antibody concentrations and different induction kinetics. The induced humoral immune response was modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-type immunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderate but 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-independent pneumococcal vaccine.

Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) Promotes M1 Repolarization of Porcine Alveolar Macrophages and Th1 Type Response

“…Recent clinical trials have now reported the strong protective effect of T-cell-inducing vaccines against a range of diseases, including HIV, malaria, influenza, tuberculosis, and cancer [ 76 ]. On the contrary, vaccination of mice with lipidated pneumococcal lipoproteins enhanced antibody-mediated immunity compared with vaccination with non-lipidated proteins, but had no significant effect on the CMI responses [ 77 ]. Another possibility is caused by ORF7 , which is involved in A2.…”

Platelets, Bacterial Adhesins and the Pneumococcus

“…All tested pneumococcal lipoproteins were heterologously expressed without the lipid moiety. The naturally occurring lipidation of lipoproteins has been shown to trigger TLR2-dependent signaling in leukocytes [ 178 , 179 ]. Therefore, lipidated proteins were tested in comparison to their non-lipidated forms [ 179 ], but no activation leading to P-selectin surface staining was detected.…”

“…The naturally occurring lipidation of lipoproteins has been shown to trigger TLR2-dependent signaling in leukocytes [ 178 , 179 ]. Therefore, lipidated proteins were tested in comparison to their non-lipidated forms [ 179 ], but no activation leading to P-selectin surface staining was detected. Nevertheless, it is noteworthy to know that TLR expression levels in resting platelets is low, but they become upregulated, and levels increase on the platelet surface upon activation [ 87 , 180 ].…”

Cognizance of posttranslational modifications in vaccines: A way to enhanced immunogenicity

“…Further, it was reported that the lipidated pneumococcal antigens (DacB and PnrA) have shown ameliorated humoral immune responses when administered in mice. Compared to non‐lipidated proteins, the lipidated modified protein was responsible for the induction of high antibody titers, hence accountable for suppressing Pneumococcus colonization (Voß et al, 2020 ).…”