Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group A streptococcus

Madge, Harrison Y. R.; Huang, Wenbin; Gilmartin, Lachlan; Rigau-Planella, Berta; Hussein, Waleed M.; Khalil, Zeinab; Koirala, Prashamsa; Santiago, Viviene S.; Capon, Robert J.; Tóth, István; Stephenson, Rachel J.

doi:10.1039/d1bm01333e

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…[58] However, more recently, higher immunostimulatory potencies of physical mixtures over conjugated systems have also been reported. [59,60] Our polymeric nanoparticle-based adjuvant can be formulated with antigen by simple mixing, omitting the highly tedious and expensive conjugation procedure.…”

Section: Discussionmentioning

confidence: 99%

Polymeric Nanoparticles as a Self‐Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Koirala

Chen

Boer

et al. 2023

Adv Funct Materials

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Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE‐J8 (PJ8), derived from Group A Streptococcus (GAS) M‐protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod‐shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)‐adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.

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Section: Discussionmentioning

confidence: 99%

Polymeric Nanoparticles as a Self‐Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Koirala

Chen

Boer

et al. 2023

Adv Funct Materials

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“…Synthesis of the cyclic lipopeptide delivery system DS-4 (Scheme ) began as per our previously published cyclic adjuvant assessed as part of a group A Streptococcus vaccine. , The cyclic carrier peptide was first synthesized in its linear conformation on 2-chlorotritylchloride (2-CTC) resin, allowing for the inclusion of four lysine amino acids (two protected by Boc and two protected by ivDde) which enabled both off resin head-to-tail cyclization and access to two orthogonal conjugation sites for lipids and/or antigen conjugation (Scheme ). Following cleavage and head-to-tail cyclization, the ivDde-protecting groups were removed with 5% hydrazine in MeOH before conjugation of Dde-C16 lipoamino acids to the free amines of the deprotected lysine side chains.…”

Section: Resultsmentioning

confidence: 99%

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion

Madge,

Alexander,

Azuar

et al. 2023

J. Med. Chem.

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Cocaine is one of the most widely used and increasingly popular illicit psychoactive drugs. Unlike other commonly used substances of abuse, cocaine has no pharmacological therapies to treat addiction or aid in rehabilitation. Immunopharmacology has long been touted as a possible avenue to develop effective anticocaine therapies; however, lack of efficacy and designs which are not consistent with simple large-scale production have hindered vaccine translation. We have designed and synthesized a peptide-based anti-cocaine immunogen which we have shown is capable of inducing physiologically relevant immune responses in mice as part of a self-adjuvanting delivery system or in combination with the human-approved commercial adjuvant MF59. We have demonstrated that immunization with the reported vaccine elicits high titers of anti-cocaine IgG and prevents cocaine-induced hyperlocomotion in an in vivo murine model. This peptide-hapten immunogen along with self-adjuvanting liposomal-based delivery system provides a platform for the development of effective anti-drug vaccines.

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“…Additionally, a physical mixture of J8-PADRE epitope with lipid peptide and cyclic decapeptide, as a vaccine candidate, was subcutaneously administrated into mice. The preclinical trial of this physical mixture induced a significantly higher J8-specific immune response compared to conjugation groups [ 119 ]. The most recent study of J8 was the evaluation of the J8-DT (J8 epitope conjugated with diphtheria toxin) vaccine, delivered by a high-density microarray patch (HD-MAP).…”

Section: Recent Advances Of Gas Vaccine Developmentmentioning

confidence: 99%

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

Fan,

Toth,

Stephenson

2024

Vaccines

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Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described

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Physical mixture of a cyclic lipopeptide vaccine induced high titres of opsonic IgG antibodies against group A streptococcus

Abstract: The presence of a cyclic peptide is as part of a physically-mixed group A Streptococcus vaccine for the induction of a strong, balanced Th1/Th2 immune response.

Cited by 6 publications

References 42 publications

Polymeric Nanoparticles as a Self‐Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Polymeric Nanoparticles as a Self‐Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Synthetic Anti-Cocaine Nanoaccine Successfully Prevents Cocaine-Induced Hyperlocomotion

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus

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