Cell-Penetrating Peptides-Based Liposomal Delivery System Enhanced Immunogenicity of Peptide-Based Vaccine against Group A Streptococcus.

Jieru Yang,Waleed M Hussein,Robert J Capon,Farrhana Firdaus,Mariusz Skwarczynski,Nirmal Marasini,Zeinab G Khalil,Istvan Toth,Armira Azuar

doi:10.3390/vaccines9050499

Abstract

Peptide-based vaccine development represents a highly promising strategy for preventing Group A Streptococcus (GAS) infection. However, these vaccines need to be administered with the help of a delivery system and/or immune adjuvant. Cell-penetrating peptides (CPPs) have been used as a powerful tool for delivering various therapeutic agents, including peptides, as they can overcome the permeability barrier of cell membranes. Here, we used CPPs to deliver our lead lipopeptide-based vaccine (LCP-1). CPPs were anchored through a spacer to LCP-1-bearing multilamellar and unilamellar liposomes and administered to Swiss outbred mice. Tat47–57 conjugated to two palmitic acids via a (Gly)6 spacer (to form a liposome-anchoring moiety) was the most efficient system for triggering immune responses when combined with multilamellar liposomes bearing LCP-1. The immunostimulatory potential of a variety of other CPPs was examined following intranasal administration in mice. Among them, LCP-1/liposomes/Tat47–57 and LCP-1/liposomes/KALA induced the highest antibody titers. The antibodies produced showed high opsonic activity against clinically isolated GAS strains D3840 and GC2 203. The use of the CPP-liposome delivery system is a promising strategy for liposome-based GAS vaccine development.

Highlights

Peptide-based subunit vaccines exhibit an improved safety profile in comparison to conventional vaccines because they utilize only small antigens derived from a target pathogen
Conjugates 1–9 were designed to carry a lipidic group as a liposome anchoring moiety: two palmitic acids conjugated to the lysine moiety were used for this purpose
Variable lengths of spacers were placed between the lipidic moieties and Tat47–57 to identify more efficient Cell-penetrating peptides (CPPs)-liposome presentations

Summary

Introduction

Peptide-based subunit vaccines exhibit an improved safety profile in comparison to conventional vaccines because they utilize only small antigens derived from a target pathogen. As such, they are free from redundant pathogen components, which reduce the possibility of inducing allergic or autoimmune responses. CPPs are a group of short peptides that have the special ability to overcome the permeability barrier of cell membranes and enter the cell interior in a non-invasive manner without assistance from membrane proteins [6] They have been thoroughly explored for delivering various cargos, such as peptides, nucleic acids, proteins, nanoparticles, and liposomes, into cells [7,8,9]. The internalization mechanisms of CPPs remain unclear, CPPs have already been employed to enhance both cellular immune responses via the delivery of antigen directly into the cytoplasm, and humoral immune responses, where antigens are delivered through the endocytic pathway [11,12,13]

Methods

Results

Conclusion