Influence of component structural arrangement on cholesterol-antigen conjugate immunogenicity and antisera bactericidal activity against group A Streptococcus.

Immune stimulants (adjuvants) are essential vaccine components; however, clinically approved adjuvants are limited with the majority being derived from pathogenic components. In this study, the adjuvanting capacity of cholesterol, a natural human lipid, was explored following conjugation with peptide antigens. A structure-activity relationship study was conducted to compare linear and branched cholesterol conjugates with other lipopeptide vaccines and commercial adjuvants.

A synthetic cyclic peptide for promoting antigen presentation and immune activation.

Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action.

Total Synthesis of Talarolide A and -Talarolide A: Hydroxamate H-Bond Bridge Stabilization of Cyclic Peptide Conformers Invokes Non-Canonical Atropisomerism.

The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A () has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring conformer stabilization. The unexpected co-synthesis of -talarolide A () revealed, for the first time, that hydroxamate H-bond bridging in the talarolide framework invokes non-canonical atropisomerism and that talarolides A (), C (), and D () all exist naturally as atropisomers. These discoveries raise the intriguing prospect that comparable functionalisation of other cyclic peptides, including those with commercial value, could provide ready access to new "unnatural atropisomeric" chemical space, with new and/or improved chemical and biological properties.

Australian Marine and Terrestrial -Derived Surugamides, and Synthetic Analogs, and Their Ability to Inhibit (Heartworm) Motility.

A bioassay-guided chemical investigation of a bacterium, sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a () and A2a () as potent inhibitors of (heartworm) microfilaria (mf) motility (EC 0.0013-0.

Cholesterol as an inbuilt immunoadjuvant for a lipopeptide vaccine against group A Streptococcus infection.

Peptide-based vaccines can trigger highly specific immune responses, although peptides alone are usually unable to confer strong humoral or cellular immunity. Consequently, peptide antigens are administered with immunostimulatory adjuvants, but only a few are safe and effective for human use. To overcome this obstacle, herein a peptide antigen was lipidated to effectively anchor it to liposomes and emulsion.

Talarolides Revisited: Cyclic Heptapeptides from an Australian Marine Tunicate-Associated Fungus, sp. CMB-TU011.

Application of a miniaturized 24-well plate system for cultivation profiling (MATRIX) permitted optimization of the cultivation conditions for the marine-derived fungus sp. CMB-TU011, facilitating access to the rare cycloheptapeptide talarolide A () along with three new analogues, B-D (-). Detailed spectroscopic analysis supported by Marfey's analysis methodology was refined to resolve -Me-l-Ala from -Me-d-Ala, l--Ile from l-Ile and l-Leu, and partial and total syntheses of , and permitted unambiguous assignment of structures for (revised) and -.

Regulation of 20α-Hydroxysteroid Dehydrogenase Expression in Term Pregnant Human Myometrium Ex Vivo.

Metabolic inactivation of progesterone within uterine myocytes by 20α-hydroxysteroid dehydrogenase (20α-HSD) has been postulated as a mechanism contributing to functional progesterone withdrawal at term. In humans, 20α-HSD is encoded by the gene AKR1C1. Myometrial AKR1C1 mRNA abundance has been reported to increase significantly during labor at term.

Activity Relationship of Poly(ethylenimine)-Based Liposomes as Group A Vaccine Delivery Systems.

Untreated group A (GAS) can lead to a range of life-threatening diseases, including rheumatic heart disease. To date, no therapeutic or prophylactic vaccines are commercially available to treat or prevent GAS infection. Development of a peptide-based subunit vaccine offers a promising solution, negating the safety issues of live-attenuated or inactive vaccines.

Optimization of an α-aminonaphthylmethylphosphonic acid inhibitor of purple acid phosphatase using rational structure-based design approaches.

Purple acid phosphatases (PAPs) are ubiquitous binuclear metallohydrolases that have been isolated from various animals, plants and some types of fungi. In humans and mice, elevated PAP activity in osteoclasts is associated with osteoporosis, making human PAP an attractive target for the development of anti-osteoporotic drugs. Based on previous studies focusing on phosphonate scaffolds, as well as a new crystal structure of a PAP in complex with a derivative of a previously synthesized α-aminonaphthylmethylphosphonic acid, phosphonates 24-40 were designed as new PAP inhibitor candidates.

The Development of Surface-Modified Liposomes as an Intranasal Delivery System for Group A Streptococcus Vaccines.

Intranasal vaccine administration can overcome the disadvantages of injectable vaccines and present greater efficiency for mass immunization. However, the development of intranasal vaccines is challenged by poor mucosal immunogenicity of antigens and the limited availability of mucosal adjuvants. Here, we examined a number of self-adjuvanting liposomal systems for intranasal delivery of lipopeptide vaccine against group A Streptococcus (GAS).

Liposomal Formulations of a Polyleucine-Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer.

Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects.

Glyclauxins A-E: Dimeric Oxaphenalenone Aminoglycosides from an Australian Wasp Nest-Derived Fungus sp. CMB-MW102.

Chemical analysis of cultures of a Queensland mud dauber wasp nest-derived fungus, sp. CMB-MW102, yielded the known dimeric oxaphenalenone duclauxin () along with a family of new 1-deoxy-d-glucosamine adducts, glyclauxins A-E (-). Despite 1D NMR spectra of - being compromised by broadening of selected resonances, structures inclusive of absolute configuration were assigned on the basis of detailed spectroscopic analysis and biogenetic considerations, as well as biomimetic semisynthesis and chemical interconversion.

Molecular characterization and genotyping of hepatitis C virus from Sudanese end-stage renal disease patients on haemodialysis.

Background: Hepatitis C virus (HCV) is a global public health problem, with ~ 11 million people in Africa infected. There is incomplete information on HCV in Sudan, particularly in haemodialysis patients, who have a higher prevalence compared to the general population. Thus, our objectives were to genotype and molecularly characterize HCV isolated from end-stage renal disease haemodialysis patients.

Development of Multilayer Nanoparticles for the Delivery of Peptide-Based Subunit Vaccine against Group A .

Peptide-based subunit vaccines include only minimal antigenic determinants, and, therefore, are less likely to induce allergic immune responses and adverse effects compared to traditional vaccines. However, peptides are weakly immunogenic and susceptible to enzymatic degradation when administered on their own. Hence, we designed polyelectrolyte complex (PEC)-based delivery systems to protect peptide antigens from degradation and improve immunogenicity.

Poly(hydrophobic Amino Acids) and Liposomes for Delivery of Vaccine against Group A Streptococcus.

Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability.

Advances in Infectious Disease Vaccine Adjuvants.

Vaccines are one of the most significant medical interventions in the fight against infectious diseases. Since their discovery by Edward Jenner in 1796, vaccines have reduced the worldwide transmission to eradication levels of infectious diseases, including smallpox, diphtheria, hepatitis, malaria, and influenza. However, the complexity of developing safe and effective vaccines remains a barrier for combating many more infectious diseases.

Peptide-Based Vaccine against SARS-CoV-2: Peptide Antigen Discovery and Screening of Adjuvant Systems.

The SARS-CoV-2 virus has caused a global crisis, resulting in 0.5 billion infections and over 6 million deaths as of March 2022. Fortunately, infection and hospitalization rates were curbed due to the rollout of DNA and mRNA vaccines.

Development of a peptide vaccine against hookworm infection: Immunogenicity, efficacy, and immune correlates of protection.

Background: Approximately 400 million individuals are infected with hookworms globally. Protective vaccines are needed to prevent reinfections, which often occur after drug treatment in endemic areas. Ideal vaccines are highly efficacious and well tolerated, and do not present risks to patient safety.

Investigation of liposomal self-adjuvanting peptide epitopes derived from conserved blood-stage Plasmodium antigens.

Malaria is a vector born parasitic disease causing millions of deaths every year. Despite the high mortality rate, an effective vaccine against this mosquito-borne infectious disease is yet to be developed. Up to date, RTS,S/AS01 is the only vaccine available for malaria prevention; however, its efficacy is low.

Structure-activity relationship of lipid, cyclic peptide and antigen rearrangement of physically mixed vaccines.

Currently there is no approved vaccine to prevent and/or treat group A Streptococcus (GAS) infection. With increasing reports of GAS antibiotic resistance, vaccine adjuvants and targeted delivery systems which induce a strong immune response are a widely acknowledged unmet need. Through extensive structure-activity studies, we investigated a cyclic decapeptide physically mixed with a GAS B cell peptide epitope (J8), a universal T helper epitope (PADRE), and different synthetic lipidic moieties as a conceivable self-adjuvanting GAS vaccine.

Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances.

Persistent infection with high-risk human papillomaviruses (HPVs), such as HPV-16 and HPV-18, can induce cervical cancer in humans. The disease carries high morbidity and mortality among females worldwide. Inoculation with prophylactic HPV vaccines, such as Gardasil or Cervarix, is the predominant method of preventing cervical cancer in females 6 to 26 years of age.

Hookworm infection: Toward development of safe and effective peptide vaccines.

Hookworms are hematophagous nematode parasites that have infected a billion people worldwide. Anthelmintic drugs have limited efficacy and do not prevent reinfection. Therefore, prophylactic vaccines are in high demand.