Immunization with a Tetraepitopic Lipid Core Peptide Vaccine Construct Induces Broadly Protective Immune Responses against Group A Streptococcus

ABSTRACT The study reported here investigated the immunogenicity and protective potential of a lipid core peptide (LCP) construct containing a conserved region determinant of M protein, defined as peptide J8. Parenteral immunization of mice with LCP-J8 led to the induction of high-titer serum immunoglobulin G J8-specific antibodies when the construct was coadministered with complete Freund's adjuvant (CFA) or administered alone. LCP-J8 in CFA had significantly enhanced immunogenicity compared with the monomeric peptide J8 given in CFA. Moreover, LCP-J8/CFA and LCP-J8 antisera opsonized four different group A streptococcal (GAS) strains, and the antisera did not cross-react with human heart tissue proteins. These data indicate the potential of an LCP-based M protein conserved region GAS vaccine in the induction of broadly protective immune responses in the absence of a conventional adjuvant.

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Lipid Core Peptide System for Gene, Drug, and Vaccine Delivery

Australian Journal of Chemistry ◽

10.1071/ch09149 ◽

2009 ◽

Vol 62 (9) ◽

pp. 956 ◽

Cited By ~ 34

Author(s):

Wei Zhong ◽

Mariusz Skwarczynski ◽

Istvan Toth

Keyword(s):

Group A Streptococcus ◽

Biologically Active ◽

Cell Permeability ◽

Vast Number ◽

Lipid Core ◽

Drug Molecules ◽

Efficient Delivery ◽

Group A ◽

Core Peptide ◽

The Stability

A vast number of biologically active compounds await efficient delivery to become therapeutic agents. Lipidation has been demonstrated to be a convenient and useful approach to improve the stability and transport across biological membranes of potential drug molecules. The lipid core peptide (LCP) system has emerged as a promising lipidation tool because of its versatile features. This review discusses the progress in the development of the LCP system to improve cell permeability of nucleotides, physicochemical properties of potential drugs, and vaccine immunogenicity. Emphasis was put on the application of the LCP system to deliver antigens for the prevention of group A streptococcus infection, novel techniques of conjugation of target molecules to the LCP, and new alterations of the LCP system itself.

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Enhancing the immunogenicity and modulating the fine epitope recognition of antisera to a helical group A streptococcal peptide vaccine candidate from the M protein using lipid‐core peptide technology

Immunology and Cell Biology ◽

10.1046/j.1440-1711.2002.01067.x ◽

2002 ◽

Vol 80 (2) ◽

pp. 178-187 ◽

Cited By ~ 27

Author(s):

Wendy A Hayman ◽

Istvan Toth ◽

Nicholas Flinn ◽

Martin Scanlon ◽

Michael F Good

Keyword(s):

Vaccine Candidate ◽

Peptide Vaccine ◽

M Protein ◽

Lipid Core ◽

Epitope Recognition ◽

Group A ◽

Core Peptide

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Lipid core peptide technology and group A streptococcal vaccine delivery

Expert Review of Vaccines ◽

10.1586/14760584.3.1.43 ◽

2004 ◽

Vol 3 (1) ◽

pp. 43-58 ◽

Cited By ~ 14

Author(s):

Colleen Olive ◽

Michael R Batzloff ◽

Istvan Toth

Keyword(s):

Vaccine Delivery ◽

Lipid Core ◽

Group A ◽

Core Peptide

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Development of Polyelectrolyte Complexes for the Delivery of Peptide-Based Subunit Vaccines against Group A Streptococcus

Nanomaterials ◽

10.3390/nano10050823 ◽

2020 ◽

Vol 10 (5) ◽

pp. 823 ◽

Cited By ~ 1

Author(s):

Lili Zhao ◽

Wanli Jin ◽

Jazmina Gonzalez Cruz ◽

Nirmal Marasini ◽

Zeinab G. Khalil ◽

...

Keyword(s):

Immune Responses ◽

Subunit Vaccine ◽

Group A Streptococcus ◽

Vaccine Delivery ◽

Surface Charges ◽

Subunit Vaccines ◽

Polyelectrolyte Complexes ◽

Humoral Immune ◽

Anionic Polymers ◽

Group A

Peptide subunit vaccines hold great potential compared to traditional vaccines. However, peptides alone are poorly immunogenic. Therefore, it is of great importance that a vaccine delivery platform and/or adjuvant that enhances the immunogenicity of peptide antigens is developed. Here, we report the development of two different systems for the delivery of lipopeptide subunit vaccine (LCP-1) against group A streptococcus: polymer-coated liposomes and polyelectrolyte complexes (PECs). First, LCP-1-loaded and alginate/trimethyl chitosan (TMC)-coated liposomes (Lip-1) and LCP-1/alginate/TMC PECs (PEC-1) were examined for their ability to trigger required immune responses in outbred Swiss mice; PEC-1 induced stronger humoral immune responses than Lip-1. To further assess the adjuvanting effect of anionic polymers in PECs, a series of PECs (PEC-1 to PEC-5) were prepared by mixing LCP-1 with different anionic polymers, namely alginate, chondroitin sulfate, dextran, hyaluronic acid, and heparin, then coated with TMC. All produced PECs had similar particle sizes (around 200 nm) and surface charges (around + 30 mV). Notably, PEC-5, which contained heparin, induced higher antigen-specific systemic IgG and mucosal IgA titers than all other PECs. PEC systems, especially when containing heparin and TMC, could function as a promising platform for peptide-based subunit vaccine delivery for intranasal administration.

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Immunogenicity and Safety of a Chemically Synthesized Divalent Group A Streptococcal Vaccine

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2018/4702152 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Yongxiang Wu ◽

Suhua Li ◽

Yanting Luo ◽

Yunyue Zhao ◽

Jiarui Wang ◽

...

Keyword(s):

Clinical Trial ◽

Amino Acids ◽

Survival Rate ◽

Protective Effect ◽

Health Problem ◽

Group A Streptococcus ◽

Peptide Vaccine ◽

Effective Vaccine ◽

Histopathological Analysis ◽

Group A

Background. Group A streptococcus (GAS) infections and poststreptococcal sequelae remain a health problem worldwide, which necessitates searching for an effective vaccine, while no licensed GAS vaccine is available. We have developed a divalent peptide vaccine composed of 84 amino acids to cover the main GAS serotypes (M1 and M12 streptococci) in China, and herein, we aimed to evaluate immunogenicity and safety of this vaccine.Methods. Mice were immunized with the vaccine. ELISA, indirect bactericidal test, and immunofluorescent assay were used to study immunogenicity. GAS challenge assay was used to test the protective effect. Safety was tested by histopathological analysis.Results. Immunized group mice (n=16) developed higher titer antibody after immunization than nonimmunized group mice (n=16) did. This antibody can deposit on the surface of GAS and promote killing of GAS, resulting in 93.1% decrease of M1 GAS and 89.5% of M12 GAS. When challenged with M1 and M12 streptococci, immunized group mice had a higher survival rate (87.5% and 75%) than nonimmunized group mice (37.5% and 25%). No autoimmune reactions were detected on organs of mice.Conclusion. The results suggest that this vaccine shows fair immunogenicity and safety, which will lead our research on GAS vaccine into clinical trial.

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FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model

Microbes and Infection ◽

10.1016/j.micinf.2014.03.006 ◽

2014 ◽

Vol 16 (5) ◽

pp. 409-418 ◽

Cited By ~ 3

Author(s):

Cuiqing Ma ◽

Zheng Liu ◽

Wenjian Li ◽

Xuesong Qian ◽

Song Zhang ◽

...

Keyword(s):

Mouse Model ◽

Immune Responses ◽

Group A Streptococcus ◽

M Protein ◽

Epitope Vaccine ◽

Group A

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Lipid Peptide Core Nanoparticles as Multivalent Vaccine Candidates against Streptococcus pyogenes

Australian Journal of Chemistry ◽

10.1071/ch11292 ◽

2012 ◽

Vol 65 (1) ◽

pp. 35 ◽

Cited By ~ 23

Author(s):

Mariusz Skwarczynski ◽

Bibi Hamideh Parhiz ◽

Fatemeh Soltani ◽

Saranya Srinivasan ◽

Khairul A. Kamaruzaman ◽

...

Keyword(s):

Streptococcus Pyogenes ◽

Subunit Vaccine ◽

Click Reaction ◽

Group A Streptococcus ◽

Vaccine Candidates ◽

Wide Range ◽

Group A ◽

Core Peptide ◽

Aqueous Conditions ◽

Peptide Core

Traditional vaccine approaches for Group A streptococcus (GAS) infection are inadequate owing to the host’s production of cross-reactive antibodies that recognize not only the bacteria but also human tissue. To overcome this problem a peptide subunit-based vaccine was proposed, which would incorporate only minimal non-cross reactive epitopes. However, special delivery systems/adjuvants were required because short peptides are not immunogenic. In this study we have incorporated two epitopes from two different GAS proteins into a lipid core peptide (LCP) self-adjuvanting delivery system to achieve better protection against a wide range of GAS serotypes. Multivalent and monovalent constructs were synthesized with the help of an azide alkyne cycloaddition (click) reaction and their ability to self-assemble under aqueous conditions was examined. The compounds significantly differed in their ability to form small size nanoparticles, which are believed to be most appropriate for peptide-based subunit vaccine delivery. The LCP conjugates possessing two different epitopes, in contrast to monoepitopic constructs, formed small nanoparticles (5–15 nm) presumably owing to a suitable hydrophilic-hydrophobic balance of the molecules.

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