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

Manmeet Bhalla,Alexsandra Abamonte,Blaine A Pfeifer,Shaunna R Simmons,Essi Y I Tchalla,Elsa N Bou Ghanem,Roozbeh Nayerhoda,Dongwon Park

doi:10.3389/fragi.2021.798868

Manmeet Bhalla, Alexsandra Abamonte + Show 6 more

Open Access

https://doi.org/10.3389/fragi.2021.798868

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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.

Highlights

Streptococcus pneumoniae is an opportunistic pathogen that asymptomatically resides in the upper respiratory tract of humans but can cause serious life-threatening infections (Kadioglu et al, 2008; Lower Respiratory Infecti, 2018)
We found that Liposomal Encapsulation of Polysaccharides (LEPS) vaccination was able to induce immunoglobulin M (IgM) production at levels that were significantly higher than the Empty LEPS and that were comparable to those induced by PCV13 (Figure 2A)
When we measured the lung bacterial burden, we observed a similar trend, with PCV13 failing to reduce the bacterial numbers compared to the Sham group (Figure 8B), while mice that received the LEPS vaccine had approximately 10-fold less bacterial burden in the lungs compared to the Sham controls (Figure 8B). These findings indicate that while vaccination with PCV13 failed to provide any protection in old mice against pneumococcal pneumonia, the LEPS vaccine boosted the ability of aged hosts to control lung infection

Summary

Introduction

Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that asymptomatically resides in the upper respiratory tract of humans but can cause serious life-threatening infections (Kadioglu et al, 2008; Lower Respiratory Infecti, 2018). These include pneumonia which can progress to invasive pneumococcal disease leading to bacteremia, meningitis, and endocarditis (van der Poll and Opal, 2009; Randle et al, 2011). To further complicate the current health concerns, elderly individuals are more at risk of acquiring drug-resistant infections (CDC, 2021) which are on a rise in S. pneumoniae (CDC, 2013)

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