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

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.

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Opsonic Activity of Conservative Versus Variable Regions of the Group A Streptococcus M Protein

Vaccines ◽

10.3390/vaccines8020210 ◽

2020 ◽

Vol 8 (2) ◽

pp. 210

Author(s):

Chuankai Dai ◽

Zeinab G. Khalil ◽

Waleed M. Hussein ◽

Jieru Yang ◽

Xiumin Wang ◽

...

Keyword(s):

Vaccine Development ◽

Group A Streptococcus ◽

Clinical Isolates ◽

M Protein ◽

Opsonic Activity ◽

Subunit Vaccines ◽

Variable Regions ◽

Global Challenge ◽

Group A ◽

Outbred Mice

Group A Streptococcus (GAS) and GAS-associated infections are a global challenge, with no licensed GAS vaccine on the market. The GAS M protein is a critical virulence factor in the fight against GAS infection, and it has been a primary target for GAS vaccine development. Measuring functional opsonic antibodies against GAS is an important component in the clinical development path for effective vaccines. In this study, we compared the opsonic activity of two synthetic, self-adjuvanting subunit vaccines containing either the J8- or 88/30-epitope in Swiss outbred mice using intranasal administration. Following primary immunization and three boosts, sera were assessed for IgG activity using ELISA, and opsonization activity against seven randomly selected clinical isolates of GAS was measured. Vaccine constructs containing the conservative J8-epitope showed significant opsonic activity against six out of the seven GAS clinical isolates, while the vaccine containing the variable 88/30-epitope did not show any significant opsonic activity.

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Molecular Epidemiology of Group A Streptococcus Infections in The Gambia

Vaccines ◽

10.3390/vaccines9020124 ◽

2021 ◽

Vol 9 (2) ◽

pp. 124

Author(s):

Sona Jabang ◽

Annette Erhart ◽

Saffiatou Darboe ◽

Aru-Kumba Baldeh ◽

Valerie Delforge ◽

...

Keyword(s):

Molecular Epidemiology ◽

Vaccine Development ◽

Group A Streptococcus ◽

Epidemiological Data ◽

The Gambia ◽

Strain Diversity ◽

Group A ◽

Considerable Strain

Molecular epidemiological data on Group A Streptococcus (GAS) infection in Africa is scarce. We characterized the emm-types and emm-clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for emm-typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.

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Vaccine Development for Group A Streptococcus Infections and Associated Diseases

Current Drug Targets ◽

10.2174/1389450043490721 ◽

2004 ◽

Vol 5 (1) ◽

pp. 57-69 ◽

Cited By ~ 15

Author(s):

M. Batzloff ◽

K. Sriprakash ◽

M. Good

Keyword(s):

Vaccine Development ◽

Group A Streptococcus ◽

Associated Diseases ◽

Group A

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Cholic Acid-based Delivery System for Vaccine Candidates against Group A Streptococcus

ACS Medicinal Chemistry Letters ◽

10.1021/acsmedchemlett.9b00239 ◽

2019 ◽

Vol 10 (9) ◽

pp. 1253-1259 ◽

Cited By ~ 4

Author(s):

Armira Azuar ◽

Lili Zhao ◽

Tsui Ting Hei ◽

Reshma J. Nevagi ◽

Stacey Bartlett ◽

...

Keyword(s):

Cholic Acid ◽

Delivery System ◽

Group A Streptococcus ◽

Vaccine Candidates ◽

Group A

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Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

Journal of Experimental Medicine ◽

10.1084/jem.20190293 ◽

2019 ◽

Vol 216 (7) ◽

pp. 1615-1629 ◽

Cited By ~ 2

Author(s):

Andreas Naegeli ◽

Eleni Bratanis ◽

Christofer Karlsson ◽

Oonagh Shannon ◽

Raja Kalluru ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Vaccine Development ◽

Group A Streptococcus ◽

Invasive Infection ◽

Invasive Infections ◽

Life Threatening ◽

Group A ◽

Specific Igg

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.

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Survey of the bp/tee genes from clinical group A streptococcus isolates in New Zealand – implications for vaccine development

Journal of Medical Microbiology ◽

10.1099/jmm.0.080804-0 ◽

2014 ◽

Vol 63 (12) ◽

pp. 1670-1678 ◽

Cited By ~ 11

Author(s):

John D. Steemson ◽

Nicole J. Moreland ◽

Deborah Williamson ◽

Julie Morgan ◽

Philip E. Carter ◽

...

Keyword(s):

New Zealand ◽

Vaccine Development ◽

Group A Streptococcus ◽

Invasive Disease ◽

T Antigen ◽

Clinical Group ◽

Wide Range ◽

Life Threatening ◽

Group A ◽

The Individual

Group A streptococcus (GAS) is responsible for a wide range of diseases ranging from superficial infections, such as pharyngitis and impetigo, to life-threatening diseases, such as toxic shock syndrome and acute rheumatic fever (ARF). GAS pili are hair-like extensions protruding from the cell surface and consist of highly immunogenic structural proteins: the backbone pilin (BP) and one or two accessory pilins (AP1 and AP2). The protease-resistant BP builds the pilus shaft and has been recognized as the T-antigen, which forms the basis of a major serological typing scheme that is often used as a supplement to M typing. A previous sequence analysis of the bp gene (tee gene) in 39 GAS isolates revealed 15 different bp/tee types. In this study, we sequenced the bp/tee gene from 100 GAS isolates obtained from patients with pharyngitis, ARF or invasive disease in New Zealand. We found 20 new bp/tee alleles and four new bp/tee types/subtypes. No association between bp/tee type and clinical outcome was observed. We confirmed earlier reports that the emm type and tee type are associated strongly, but we also found exceptions, where multiple tee types could be found in certain M/emm type strains, such as M/emm89. We also reported, for the first time, the existence of a chimeric bp/tee allele, which was assigned into a new subclade (bp/tee3.1). A strong sequence conservation of the bp/tee gene was observed within the individual bp/tee types/subtypes (>97 % sequence identity), as well as between historical and contemporary New Zealand and international GAS strains. This temporal and geographical sequence stability provided further evidence for the potential use of the BP/T-antigen as a vaccine target.

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