Article
Pharmacology & Pharmacy
Abdin Shakirin Mohamad Norpi, Muhammad Luqman Nordin, Nuraziemah Ahmad, Haliza Katas, Abdullah Al-Hadi Ahmad Fuaad, Asif Sukri, Nirmal Marasini, Fazren Azmi
Summary: Two variants of nanoparticle-based vaccines against group A streptococcus (GAS) were developed in this study. The vaccines, composed of encapsulated KLH protein and lipidated M-protein derived B cell peptide epitope, showed high antigen-specific antibody titres and opsonic activity against GAS strains in immunized mice.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yuan Gao, Xiaochen Gong, Shuang Yu, Zheng Jin, Qicheng Ruan, Chunjing Zhang, Kai Zhao
Summary: The study found that N-2-Hydroxypropyl trimethyl ammonium chloride chitosan/N, O-carboxymethyl chitosan nanoparticles (N-2-HACC/CMCS NPs) showed good immunogenicity and no toxicity as a universal vaccine adjuvant/delivery system. The prepared N-2-HACC/OVA/CMCS NPs induced higher levels of antibodies and immune responses in mice, suggesting their potential in enhancing humoral, cellular, and mucosal immune responses.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Immunology
Armira Azuar, Harrison Y. R. Madge, Jennifer C. Boer, Jazmina L. Gonzalez Cruz, Jingwen Wang, Zeinab G. Khalil, Cyril Deceneux, Georgia Goodchild, Jieru Yang, Prashamsa Koirala, Waleed M. Hussein, Robert J. Capon, Magdalena Plebanski, Istvan Toth, Mariusz Skwarczynski
Summary: Adjuvants and delivery systems are crucial for enhancing immunogenicity of peptide-based vaccines. A poly(hydrophobic amino acids) delivery system self-assembles into nanoparticles with self-adjuvating ability, which can be further integrated into liposomes to boost immunological responses. Anchoring polyleucine-based conjugates to cationic liposomes induces significant mucosal and systemic immunity in mice.
Article
Chemistry, Medicinal
Armira Azuar, Zhuoqing Li, Mohini A. Shibu, Lili Zhao, Yacheng Luo, Ahmed O. Shalash, Zeinab G. Khalil, Robert J. Capon, Waleed M. Hussein, Istvan Toth, Mariusz Skwarczynski
Summary: The study demonstrates the potential of self-adjuvanting poly(hydrophobic amino acids) as a delivery system for peptide-based vaccines against Group A Streptococcus (GAS). Conjugates with a linear arrangement of J8-PADRE and leucine were found to induce equally effective or even better immune responses compared to commercial adjuvants. The developed adjuvant-free vaccine based on single molecule successfully elicited antibodies capable of killing GAS bacteria.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Tomoaki Kurosaki, Yuki Katafuchi, Junya Hashizume, Hitomi Harasawa, Hiroo Nakagawa, Mikiro Nakashima, Tadahiro Nakamura, Chikamasa Yamashita, Hitoshi Sasaki, Yukinobu Kodama
Summary: Pulmonary administration of the OVA/BK/gamma-PGA complex effectively induced mucosal immunity, leading to high levels of antibodies without observed in vivo toxicities.
Article
Immunology
Jieru Yang, Farrhana Firdaus, Armira Azuar, Zeinab G. Khalil, Nirmal Marasini, Robert J. Capon, Waleed M. Hussein, Istvan Toth, Mariusz Skwarczynski
Summary: Utilizing cell-penetrating peptides for delivering lipopeptide-based vaccines combined with multilamellar liposomes can efficiently trigger immune responses and generate high antibody titers with high opsonic activity against pathogenic GAS strains. This approach shows promising potential for liposome-based GAS vaccine development.
Article
Chemistry, Applied
Sen Li, Hongyan Lv, Yu Chen, Hongdong Song, Yu Zhang, Shuo Wang, Lei Luo, Xiao Guan
Summary: This study developed vitexin-loaded bilayer nanoparticles to improve the bioavailability of vitexin. The nanoparticles protected vitexin from release in the stomach and promoted sustained release in the intestine. Furthermore, the nanoparticles increased the antioxidant activity of vitexin.
CARBOHYDRATE POLYMERS
(2022)
Article
Biochemistry & Molecular Biology
Aldo Y. Tenorio-Barajas, Maria de la L. Olvera, Gabriel Romero-Paredes, Victor Altuzar, Efrain Garrido-Guerrero, Claudia Mendoza-Barrera
Summary: This work proposes a modified method using microfluidics combined with the microemulsion technique to manufacture chitosan nanoparticles. The synthesized nanoparticles showed improved size control and distribution compared to batch synthesis. The total encapsulation of IgG protein was confirmed during the fabrication of chitosan/IgG-loaded nanoparticles. The proposed materials have the potential to be used as carrier-delivery systems.
Article
Engineering, Environmental
Valquiria Campos, Diego Gouveia Marques, Joao Nogueira, Carlos O. Amorim, Ana Luisa Daniel-da-Silva, Tito Trindade
Summary: Metoprolol, a commonly used beta-blocker for treating hypertension, has been found in significant amounts in surface waters, causing negative impacts on the environment and human health. Current water treatment procedures are ineffective in removing metoprolol, highlighting the need for more efficient water treatments. This study investigates the use of magnetic nanoparticles coated with silica and.-polyglutamic acid as sorbents to capture metoprolol dissolved in water.
JOURNAL OF ENVIRONMENTAL CHEMICAL ENGINEERING
(2023)
Article
Chemistry, Physical
Suhas Gotla, Silvina Matysiak
Summary: Neurodegeneration in Alzheimer's disease is caused by abnormal accumulation of amyloid-beta (Aβ) peptides. Chitosan (CHT), a macromolecule, has been found to inhibit the aggregation of Aβ and reduce neurotoxicity. Molecular dynamics simulations showed that CHT binds and sequesters Aβ peptides, limiting their aggregation. CHT also reshapes the conformational landscapes of Aβ peptides, depending on its concentration and cationicity, which could guide the development of CHT-based materials for Alzheimer's treatment.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Pharmacology & Pharmacy
Jolynn Kiong, Ummey Jannatun Nahar, Shengbin Jin, Ahmed O. Shalash, Jiahui Zhang, Prashamsa Koirala, Zeinab G. Khalil, Robert J. Capon, Mariusz Skwarczynski, Istvan Toth, Waleed M. Hussein
Summary: Peptide-based subunit vaccines have lower risk of allergic immune responses and adverse effects compared to traditional vaccines. However, they are weakly immunogenic and susceptible to enzymatic degradation. This study designed a polyelectrolyte complex (PEC)-based delivery system to protect peptide antigens and improve their immunogenicity. The modified PEC system showed improved immune response.
Article
Immunology
Yang Xu, Ziyou Zhou, Brad Brooks, Tammy Ferguson, Judy Obliosca, Jing Huang, Izumi Kaneko, Shiroh Iwanaga, Masao Yuda, Yukiko Tsuji, Huitang Zhang, Christina C. Luo, Xunqing Jiang, Xiang-Peng Kong, Moriya Tsuji, Christopher K. Tison
Summary: Developing a safe and effective malaria vaccine is critical in reducing the spread and resurgence of the disease, especially in children. Vaccine technology has seen advancements in the development of subunit protein, peptide, and nucleic acid vaccines, which offer advantages such as safety, immune response adaptability, simple storage requirements, easier production, and lower cost. However, these new vaccine technologies often have low efficacy. A challenge in malaria vaccine development is the complex life cycle and multiple stages of the Plasmodium organism. Targeting multistage antigens simultaneously is crucial for an effective vaccine. Scientists have designed a layer-by-layer antigen delivery platform specifically engineered for malaria vaccines, which has shown promising results in inducing immune responses and providing protection in animal studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
James B. Dale, Michelle P. Aranha, Thomas A. Penfound, Sanaz Salehi, Jeremy C. Smith
Summary: This study used peptide structural algorithms to predict immunological cross-reactivity among the most prevalent M types of Strep A, and constructed a 32-valent vaccine. The vaccine showed good immunogenicity and cross-reactivity in experiments, with potential global coverage.
Article
Immunology
Joseph A. Lewnard, Laura M. King, Katherine E. Fleming-Dutra, Ruth Link-Gelles, Chris A. Van Beneden
Summary: This study estimated healthcare visit rates and antibiotic prescription rates in the United States, and predicted the potential effects of vaccines targeting Group A Streptococcus under different dosing schedules. The results showed that the vaccine has the potential to prevent pharyngitis infections and related antibiotic use.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Stephen Wan Leung, Po-Ching Cheng, Chih-Ming Chou, Chi Lin, Yu-Chieh Kuo, Yu-Lin Amy Lee, Cheng-Yang Liu, Fwu-Long Mi, Chia-Hsiung Cheng
Summary: This study demonstrated that low-molecular-weight chitosan could be utilized for gene delivery into zebrafish larvae, enhancing ISG expression, with potential implications for aquaculture applications. The delivery efficiency of LMWCSrNPs was highest at a weight ratio of 20:8:1.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Immunology
Armira Azuar, Harrison Y. R. Madge, Jennifer C. Boer, Jazmina L. Gonzalez Cruz, Jingwen Wang, Zeinab G. Khalil, Cyril Deceneux, Georgia Goodchild, Jieru Yang, Prashamsa Koirala, Waleed M. Hussein, Robert J. Capon, Magdalena Plebanski, Istvan Toth, Mariusz Skwarczynski
Summary: Adjuvants and delivery systems are crucial for enhancing immunogenicity of peptide-based vaccines. A poly(hydrophobic amino acids) delivery system self-assembles into nanoparticles with self-adjuvating ability, which can be further integrated into liposomes to boost immunological responses. Anchoring polyleucine-based conjugates to cationic liposomes induces significant mucosal and systemic immunity in mice.
Review
Immunology
Jingyi Fan, Shengbin Jin, Lachlan Gilmartin, Istvan Toth, Waleed M. Hussein, Rachel J. Stephenson
Summary: Vaccines are crucial in fighting infectious diseases, and the development of safe and effective vaccines is a challenge. Immune stimulants, or adjuvants, play a vital role in vaccine development by enhancing and prolonging immune responses. However, the potential for adverse effects must be carefully managed. Understanding the efficacy and safety mechanisms of adjuvants is essential for vaccine administration.
Article
Plant Sciences
Sarani Kankanamge, Zeinab G. Khalil, Thulasi Sritharan, Robert J. Capon
Summary: This study used GNPS and MATRIX technologies to discover a new series of indole diterpenes from an Australian marine-derived fungus, with potential application in the treatment of glaucoma, cancer, neurodegenerative diseases, as well as insecticides and antivirals.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Immunology
Jieru Yang, Jennifer C. Boer, Mattaka Khongkow, Sarunya Phunpee, Zeinab G. Khalil, Sahra Bashiri, Cyril Deceneux, Georgia Goodchild, Waleed M. Hussein, Robert J. Capon, Uracha Ruktanonchai, Magdalena Plebanski, Istvan Toth, Mariusz Skwarczynski
Summary: Intranasal vaccine administration has advantages in mass immunization. A new liposomal system using lipidated chitosan derivative (OTMC) showed promising results in stimulating high systemic antibody titers against group A Streptococcus (GAS) in mice. OTMC was more effective than the traditional trimethyl chitosan formulation and could enhance the immune responses of the vaccine without the need for a liposome delivery system. Importantly, OTMC also stimulated cytokine production by dendritic cells, indicating its potential for mucosal vaccine development.
Article
Chemistry, Medicinal
Rachel J. J. Stephenson, Istvan Toth
Summary: Cocaine is a widely used illegal drug that has significant medical and social consequences. The lack of effective pharmacological treatments has led to the development of anti-cocaine vaccines. Despite years of research, no approved pharmacological treatments exist to help individuals overcome cocaine addiction or prevent relapse.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Viet Tram Duong, Prashamsa Koirala, Sung-Po R. Chen, Michael J. Monteiro, Mariusz Skwarczynski, Istvan Toth
Summary: Porcine circovirus 2 (PCV2) infection is a serious threat to the swine industry. Novel multiepitope vaccines based on the PCV2b variant have been developed, which show strong potential for further development. Mice immunized with these vaccine candidates produced high antibody titers, indicating their effectiveness in generating an immune response against PCV2.
Article
Instruments & Instrumentation
Frazer Sinclair, Anjuman A. Begum, Charles C. Dai, Istvan Toth, Peter M. Moyle
Summary: The CRISPR/Cas9 genome editing system is a groundbreaking technology that has revolutionized genome editing for therapeutic, diagnostic, and precision medicine applications. The safe and efficient delivery of the CRISPR/Cas9 system has been a critical challenge. Viral vectors have shown promise, but face limitations for clinical applications. Nonviral delivery vectors, such as lipid, polymer, peptides, and inorganic nanoparticle-based systems, have emerged as viable alternatives. This review discusses the molecular mechanisms of CRISPR/Cas9, current delivery strategies, approaches for reducing off-target editing, and future directions for clinical trials.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Farrhana Z. Z. Firdaus, Stacey Bartlett, Waleed M. M. Hussein, Lantian Lu, Quentin Wright, Wenbin Huang, Ummey J. J. Nahar, Jieru Yang, Mattaka Khongkow, Margaret Veitch, Prashamsa Koirala, Uracha R. R. Ruktanonchai, Michael J. J. Monteiro, Jazmina L. Gonzalez L. Cruz, Rachel J. J. Stephenson, James W. W. Wells, Istvan Toth, Mariusz Skwarczynski
Summary: Human papilloma virus (HPV) is responsible for all cases of cervical cancer. Peptide-based vaccines, such as 8Qm conjugated to polyleucine, show promise as a therapeutic option with fewer side effects compared to chemotherapy and surgery. Liposomes incorporating the 8Qm conjugate demonstrated efficacy in tumor eradication, while the introduction of DC-targeting moieties did not significantly improve vaccine efficacy.
Article
Chemistry, Medicinal
Harrison Y. R. Madge, Suzy Alexander, Armira Azuar, Jiahui Zhang, Prashamsa Koirala, Thomas H. Burne, Istvan Toth, Rachel J. Stephenson
Summary: Researchers have developed a peptide-based anti-cocaine vaccine that can induce immune responses in mice, providing a platform for the development of effective anti-drug vaccines.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Angela A. Salim, Waleed M. Hussein, Pradeep Dewapriya, Huy N. Hoang, Yahao Zhou, Kaumadi Samarasekera, Zeinab G. Khalil, David P. Fairlie, Robert J. Capon
Summary: The application of a miniaturized 24-well plate system allowed for the optimization of cultivation conditions for the marine-derived fungus Talaromyces sp. CMB-TU011, leading to the discovery of a rare cycloheptapeptide talarolide A and three new analogues. Detailed spectroscopic analysis, supported by Marfey's analysis methodology, helped confirm the structures of these compounds. The investigation of hydroxamates' influence on cyclic peptide conformation through ROESY correlations and solution structure determination offers insights into the potential use of hydroxamates as molecular bridges for accessing new cyclic peptide conformations.
Article
Chemistry, Medicinal
Shengbin Jin, Jiahui Zhang, Ummey J. Nahar, Wenbin Huang, Nedaa A. Alharbi, Ahmed O. Shalash, Prashamsa Koirala, Jieru Yang, Jolynn J. E. Kiong, Zeinab G. Khalil, Robert J. Capon, Rachel J. Stephenson, Mariusz Skwarczynski, Istvan Toth, Waleed M. Hussein
Summary: Untreated group A Streptococcus (GAS) infections can be life-threatening, but there are no commercially available vaccines to treat or prevent them. Peptide-based subunit vaccines, combined with immunestimulants and/or vaccine delivery platforms, show promise in improving immunogenicity. This study investigated the use of polyelectrolyte complexes (PECs) and polymer-coated liposomes as self-adjuvanting vehicles for GAS peptide antigens delivery. The results showed that both PECs and liposomes induced strong immune responses, with liposomes having more pronounced effects.
ACS INFECTIOUS DISEASES
(2023)
Article
Materials Science, Multidisciplinary
Adel Szerlauth, Arpad Varga, Tamara Madacsy, Daniel Sebok, Sahra Bashiri, Mariusz Skwarczynski, Istvan Toth, Jozsef Maleth, Istvan Szilagyi
Summary: Incorporation of antioxidant enzymes into nanostructures provides a highly efficient and robust biocatalytic system for scavenging reactive oxygen species. The immobilized enzymes effectively reduce intracellular oxidative stress and prevent DNA damage induced by hydrogen peroxide. These findings are important for designing complex nanostructures with multienzymatic antioxidant activities.
ACS MATERIALS LETTERS
(2023)