Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

Abstract

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged ≥65 years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2–3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18–22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

The Age-Driven Decline in Neutrophil Function Contributes to the Reduced Efficacy of the Pneumococcal Conjugate Vaccine in Old Hosts

“…Antibody levels against heat-killed S. pneumoniae TIGR4 were measured by ELISA as previously described ( Bou Ghanem et al., 2018 ; Tchalla et al., 2020 ; Bhalla et al., 2021 ).…”

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine

“…Sera collected 4-weeks post vaccination were incubated with TIGR4 at 10- and 20% of total assay volume in HBSS (with Ca 2+ and Mg 2+ ). In prior work we found that at least 10% sera were required to neutralize bacterial binding to the pulmonary epithelium and no neutralization is observed with lower concentrations even with standard sera from hyperimmune mice (32). After a 30-minute incubation at 37°C, the sera/bacteria mix was added to H292 cells, the plates spun down to facilitate host-bacterial interaction and incubated for 1 hr at 37°C/CO 2 .…”

“…Antibodies in sera were assessed using an ELISA assay as previously described (12, 32, 33). Briefly, Nunc-maxisorp plates (Thermo Scientific) were coated at 4°C overnight with 2×10 5 colony forming unit (CFU) per well of heat killed Streptococcus pneumoniae serotype 4.…”

“…The ability of antibodies to neutralize binding of the pneumococcus to epithelial cells was measured using H292 human pulmonary mucoepidermoid carcinoma derived cells (ATCC) as previously described (32, 34). Briefly, 2.5×10 5 epithelial cells were seeded in tissue culture-treated flat bottom 96-well plates (Corning) and adhered overnight.…”

Safety and Prophylactic Efficacy of Liposome-Based Vaccine against the Drug-Resistant Acinetobacter baumannii in Mice

“…A liposomal formulation of adjuvant DMT (consisting of dimethyldioctadecylammonium, monophosphoryl lipid A, and trehalose 6,6′-dibehenate) enhanced the prophylactic efficacy of the DNA vaccine against Mycobacterium tuberculosis infection in mice [ 19 ]. Bhalla et al, demonstrated that a liposomal formulation of polysaccharides successfully protected aged mice against pulmonary pneumococcal infection [ 20 ]. Liposomes composed of E. coli lipids (Escheriosomes) and loaded with Salmonella typhimurium antigens induced the generation of the cytotoxic T lymphocyte (CTL) responses that effectively protected mice against bacterial infection [ 21 ].…”