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In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity. [ABSTRACT FROM AUTHOR]

ABSTRACTA major driver for the recent investment surge in bispecific antibody (bsAb) platforms and products is the multitude of distinct mechanisms of action that bsAbs offer compared to a combination of two monoclonal antibodies. Four bsAb products were granted first regulatory approvals in the US or EU during 2023 and the biopharmaceutical industry pipeline is brimming with bsAb candidates across a broad range of therapeutic applications. In previously reported bsAb discovery campaigns, following a hypothesis-based choice of two specific target proteins, selections and screening activities have often been performed in mono-specific formats. The conversion to bispecific modalities has usually been positioned toward the end of the discovery process and has involved small numbers of lead molecules, largely due to challenges in expressing, purifying, and analyzing large numbers of bsAbs. In this review, we discuss emerging strategies to facilitate the production of expanded bsAb panels, focusing particularly upon combinatorial methods to generate bsAb matrices. Such technologies will enable screening in. bispecific formats at earlier stages of discovery campaigns, not only widening the accessible protein space to maximize chances of success, but also advancing empirical bi-target validation activities to assess initial target selection hypotheses.

Researchers have made significant efforts to attach peptides to various biomaterials, resulting in diverse functionalities. By harnessing the advantages of peptides, functions such as high specificity, potency, cost-effectiveness, small size for improved tissue penetration and targeted delivery, biodegradability, and novel therapeutic applications can be achieved through their attachment to biomaterials. Of various methods available for modifying biomolecules, chemical techniques are the most established and can effectively immobilize the desired molecule onto a specific surface. This article provides a comprehensive overview of the chemical modification methods used for attaching peptides to various biomaterials in recent studies and showcases some of their latest applications. [ABSTRACT FROM AUTHOR]

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicity.

Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin–avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer.

Molecular chaperones play vital roles in various physiological reactions by regulating the folding and assembly of biomacromolecules. We have demonstrated that cationic comb-type copolymers exhibit chaperone activity for anionic biomolecules including DNA and ionic peptide via the formation of soluble interpolyelectrolyte complexes. The development of smart artificial chaperones that can be spatiotemporally controlled by a remotely guided signal would expand the functions of artificial chaperones. Herein, to enable photocontrol of chaperone activity, a cationic comb-type copolymer bearing malachite green as a photoresponsive unit was designed. We first prepared a series of carboxylic acid derivatives of malachite green identified a derivative that could be quickly and quantitatively converted to the cationic form from the nonionic form by photoirradiation. This derivative was conjugated to the cationic comb-type copolymer, poly(allylamine)-graft-poly(ethylene glycol) through a condensation reaction. Upon photoirradiation, the copolymer bearing 9 mol% malachite green enhanced the membrane disruptive activity of acidic peptide E5 and induced morphological changes in liposomes. This demonstration of photoresponsive activation of chaperoning activity of a copolymer suggests that the installation of carboxyl derivatives of malachite green will impart photoresponsiveness to various materials including biopolymers. [ABSTRACT FROM AUTHOR]

A bioluminescent immunoassay system was developed to determine serine/threonine protein kinase activity using an aequorin-labeled monoclonal antibody and a synthetic peptide as the substrate. A monoclonal antibody against the synthetic phosphorylated serine peptide (K9P peptide) of histone H3 (19 amino acid residues), referred to as the H3S10P antibody, was chemically conjugated to maleimide-activated aequorin to prepare aequorin-labeled H3S10P (AQ-S-H3S10P). For the serine/threonine kinase assay, a non-phosphorylated serine peptide (K9C peptide) coated on a microplate was incubated with serine/threonine protein kinase in the presence of ATP and Mg2+. The resulting phosphorylated K9C peptides (K9P peptide) were identified using AQ-S-H3S10P. Thus, after the removal of unbound AQ-S-H3S10P though washing, the serine/threonine kinase activity was determined by the luminescence activity of aequorin from AQ-S-H3S10P bound to the K9P peptide. This assay system, in combination with the K9C peptide and AQ-S-H3S10P, could be used to screen inhibitors of various serine/threonine protein kinases in general. [Display omitted] • The K9C peptide of histone H3 is used as a substrate for Ser/Thr protein kinase. • A monoclonal antibody against phosphorylated K9C peptide was labeled with aequorin. • Phosphorylated K9C peptide is detected using an aequorin-labeled antibody. • Ser/Thr kinase activity was determined with luminescence activity of aequorin. • Inhibition on Ser/Thr kinase by chemicals is determined by aequorin activity. [ABSTRACT FROM AUTHOR]

This communication presents the results of studies of coherently synchronized reactions of 2-picoline oxidation with hydrogen peroxide and nitrous oxide (I) in the gas phase. Optimal conditions for obtaining target products in these reactions are revealed. The influence of the process parameters on the value of the determinant in the reactions: dealcodimerization of 2-picoline with hydrogen peroxide and dimerization of 2-picoline with nitrous oxide (I) is shown. Calculated in the reaction of dealcodimerization of 2-picoline with hydrogen peroxide, the determinant of chemical conjugation has a value of D = 0.17 under optimal conditions, which indicates the induced character of dealcodimerization of 2-picoline. Based on this value, a quantitative assessment of the influence of the primary reaction (decomposition of hydrogen peroxide) on the secondary one (dealcodimerization of 2-picoline) was given. In the reaction of dimerization of 2-picoline with nitrous oxide (I), the chemical conjugation determinant has, under optimal conditions, a value of D = 0.54, which, according to the chemical interference scale, is in the region of chemical conjugation, when the primary reaction (the decomposition of nitrous oxide (I)) accelerates the secondary reaction (dimerization of 2-picoline). [ABSTRACT FROM AUTHOR]

Cetuximab is a monoclonal antibody blocking the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). However, cetuximab treatment has no clinical benefits in patients affected by mCRC with KRAS mutation or in the presence of constitutive activation of signalling pathways acting downstream of the EGFR. The aim of this study was to improve cetuximab's therapeutic action by conjugating cetuximab with the type 1 ribosome inactivating protein (RIP) quinoin isolated from quinoa seeds. A chemical conjugation strategy based on the use of heterobifunctional reagent succinimidyl 3-(2-pyridyldithio)propionate (SPDP) was applied to obtain the antibody-type 1 RIP chimeric immunoconjugate. The immunotoxin was then purified by chromatographic technique, and its enzymatic action was evaluated compared to quinoin alone. Functional assays were performed to test the cytotoxic action of the quinoin cetuximab immunoconjugate against the cetuximab-resistant GEO-CR cells. The novel quinoin cetuximab immunoconjugate showed a significant dose-dependent cytotoxicity towards GEO-CR cells, achieving IC50 values of 27.7 nM (~5.0 μg/mL) at 72 h compared to cetuximab (IC50 = 176.7 nM) or quinoin (IC50 = 149.3 nM) alone assayed in equimolar amounts. These results support the therapeutic potential of quinoin cetuximab immunoconjugate for the EGFR targeted therapy, providing a promising candidate for further development towards clinical use in the treatment of cetuximab-resistant metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

In subunit vaccines, aluminum salts (Alum) are commonly used as adjuvants, but with limited cellular immune responses. To overcome this limitation, CpG oligodeoxynucleotides (ODNs) have been used in combination with Alum. However, current combined usage of Alum and CpG is limited to linear mixtures, and the underlying interaction mechanism between CpG and Alum is not well understood. Thus, we propose to chemically conjugate Alum nanoparticles and CpG (with 5′ or 3′ end exposed) to design combination adjuvants. Our study demonstrates that compared to the 3′-end exposure, the 5′-end exposure of CpG in combination adjuvants (Al-CpG-5′) enhances the activation of bone-marrow derived dendritic cells (BMDCs) and promotes Th1 and Th2 cytokine secretion. We used the SARS-CoV-2 receptor binding domain (RBD) and hepatitis B surface antigen (HBsAg) as model antigens to demonstrate that Al-CpG-5′ enhanced antigen-specific antibody production and upregulated cytotoxic T lymphocyte markers. Additionally, Al-CpG-5′ allows for coordinated adaptive immune responses even at lower doses of both CpG ODNs and HBsAg antigens, and enhances lymph node transport of antigens and activation of dendritic cells, promoting T fh cell differentiation and B cell activation. Our novel Alum-CPG strategy points the way towards broadening the use of nanoadjuvants for both prophylactic and therapeutic vaccines. A combination adjuvant system is constructed by covalently conjugating engineered aluminum oxyhydroxide nanoparticles with different ends of CpG, in order to investigate their immunostimulatory effects. The results demonstrate that the combination adjuvants, with the 5′ end of CpG exposed, induce enhanced and balanced immune responses in both SARS-CoV-2 RBD and HBV vaccines. This finding provides insight for a more rational design of nanomaterial-based adjuvants for prophylactic and therapeutic vaccines. [Display omitted] [ABSTRACT FROM AUTHOR]

Epitope-based vaccine is a promising personalized cancer immunotherapy; however, a simple and effective approach for its bulk manufacturing is challenging. Current vaccination strategies complicate the process by introducing unnecessary components such as additional delivery carriers, and assembly units. Herein, a type of toll-like receptor 7/8 agonist-epitope conjugate (termed as TLR7/8a-epitope) has been developed as a self-assembled and carrier-free nano vaccine platform, which effectively introduces the antigen and adjuvant with maximum precision, resulting in significantly enhanced dendritic cells (DCs) activation through the MyD88-dependent TLR signaling pathway. TLR7/8a-epitope nanovaccine can prolong the local retention and increase drainage efficiency into the lymph node, eliciting a significantly higher level of CD8 T-cell immunity than those of conventional vaccine formulations. The immunization with TLR7/8a-epitope nanovaccine in mice can not only resist the invasion of B16 cancer cells, but also produce significant therapeutic effects against established B16 melanoma tumors. Therefore, the TLR7/8a-epitope nanovaccine, developed by the direct chemical conjugation of antigen peptide with immunoadjuvant, has great advantages of clear and leanest compositions, controllable and definite preparation process, and remarkable therapeutic effects, representing a new appraoch for personalized cancer immunotherapy. Herein, a kind of toll-like receptor 7/8 agonist-epitope conjugate was developed and spontaneously self-assemble into nanostructure in aqueous solution without the use of any additional constituents, which can be termed as unique carrier-free nanovaccine platform, providing effectually the leanest vaccine components with maximally and precisely loading of antigen and adjuvant. Significantly, the nanovaccine augmented the immunogenicity of antigenic peptide by increasing DCs activation through MyD88-mediated TLR signaling pathways and promoting T-cell priming. Moreover, nanovaccines could prolong the local retention and further increase the efficiency of drainage into dLNs, which was contributing to efficient initiation of epitope-specific memory and effector T-cell immune responses, leading to effective prophylactic and therapeutic antitumor effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Generalized-Modules-for-Membrane-Antigens (GMMA) is a technology platform developed to design outer membrane vesicle (OMV)-based vaccines. GMMA are basically OMVs derived from a bacterial strain specifically engineered to obtain a fit-for-purpose and affordable vaccine by potentiating, or deleting, expression of specific genes. OMVs can be used as a carrier for antigens by inducing their expression on them, with the aim to improve antigen immunogenicity and design multivalent combination vaccines. We expanded this finding to show that the chemical conjugation of different proteic and/or polysaccharidic antigens, to GMMA, is a methodology complementary to the genetic manipulation to obtain highly effective combination vaccines. Here we discuss our findings with a specific focus on the impact that GMMA technology can have on global health, as this technology platform is particularly suited to support the development of affordable vaccines for low-income countries. We believe that it is critical to elucidate the mode of action of GMMA immunogenicity and have provided a summarized description of the immunological questions to be addressed in the near future. The improved knowledge of GMMA might lead to designing more effective and safer GMMA-based vaccines to tackle the most serious vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Cetuximab is a monoclonal antibody blocking the epidermal growth factor receptor (EGFR) in metastatic colorectal cancer (mCRC). However, cetuximab treatment has no clinical benefits in patients affected by mCRC with KRAS mutation or in the presence of constitutive activation of signalling pathways acting downstream of the EGFR. The aim of this study was to improve cetuximab’s therapeutic action by conjugating cetuximab with the type 1 ribosome inactivating protein (RIP) quinoin isolated from quinoa seeds. A chemical conjugation strategy based on the use of heterobifunctional reagent succinimidyl 3-(2-pyridyldithio)propionate (SPDP) was applied to obtain the antibody-type 1 RIP chimeric immunoconjugate. The immunotoxin was then purified by chromatographic technique, and its enzymatic action was evaluated compared to quinoin alone. Functional assays were performed to test the cytotoxic action of the quinoin cetuximab immunoconjugate against the cetuximab-resistant GEO-CR cells. The novel quinoin cetuximab immunoconjugate showed a significant dose-dependent cytotoxicity towards GEO-CR cells, achieving IC50 values of 27.7 nM (~5.0 μg/mL) at 72 h compared to cetuximab (IC50 = 176.7 nM) or quinoin (IC50 = 149.3 nM) alone assayed in equimolar amounts. These results support the therapeutic potential of quinoin cetuximab immunoconjugate for the EGFR targeted therapy, providing a promising candidate for further development towards clinical use in the treatment of cetuximab-resistant metastatic colorectal cancer.

The public health burden caused by pathogenic Gram-negative bacteria is increasingly prominent due to antimicrobial resistance. The surface carbohydrates are potential antigens for vaccines against Gram-negative bacteria. The enhanced immunogenicity of the O-specific polysaccharide (O-SP) moiety of LPS when coupled to a carrier protein may protect against bacterial pathogens. However, because of the toxic lipid A moiety and relatively high costs of O-SP isolation, LPS has not been a popular vaccine antigen until recently. In this review, we discuss the rationales for developing LPS-based glycoconjugate vaccines, principles of glycoconjugate-induced immunity, and highlight the recent developments and challenges faced by LPS-based glycoconjugate vaccines. Advances in LPS harvesting, LPS chemical synthesis, and newer carrier proteins in the past decade have propelled LPS-based glycoconjugate vaccines toward further development, through to clinical evaluation. The development of LPS-based glycoconjugates offers a new horizon for vaccine prevention of Gram-negative bacterial infection. [ABSTRACT FROM AUTHOR]

Bispecific antibodies have drawn considerate research interests for therapeutic development. Numerous genetic and chemical methods are established to produce bispecific antibodies with varied formats. This protocol describes a novel approach to the synthesis of bispecific antibodies by utilizing chemically functionalized poly-ADP-ribose polymers derived from post-translational poly-ADP-ribosylation. Basic Protocol 1 includes experimental procedures for expressing and purifying recombinant full-length human poly-ADP-ribose polymerase 1 (PARP1) as well as monoclonal antibodies targeting T-cell CD3 and breast cancer tumor-associated human epidermal growth factor receptor 2 (HER2) molecules. Basic Protocol 2 details methods for enzymatic preparation of functionalized poly-ADP-ribose polymers by PARP1 and chemical conjugation of antibody molecules for bispecific antibody production. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Expression and purification of PARP1 and antibodies Basic Protocol 2: PARP1 auto-modification and antibody conjugation., (© 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Molecular chaperones play vital roles in various physiological reactions by regulating the folding and assembly of biomacromolecules. We have demonstrated that cationic comb-type copolymers exhibit chaperone activity for anionic biomolecules including DNA and ionic peptide via the formation of soluble interpolyelectrolyte complexes. The development of smart artificial chaperones that can be spatiotemporally controlled by a remotely guided signal would expand the functions of artificial chaperones. Herein, to enable photocontrol of chaperone activity, a cationic comb-type copolymer bearing malachite green as a photoresponsive unit was designed. We first prepared a series of carboxylic acid derivatives of malachite green identified a derivative that could be quickly and quantitatively converted to the cationic form from the nonionic form by photoirradiation. This derivative was conjugated to the cationic comb-type copolymer, poly(allylamine)- graft -poly(ethylene glycol) through a condensation reaction. Upon photoirradiation, the copolymer bearing 9 mol% malachite green enhanced the membrane disruptive activity of acidic peptide E5 and induced morphological changes in liposomes. This demonstration of photoresponsive activation of chaperoning activity of a copolymer suggests that the installation of carboxyl derivatives of malachite green will impart photoresponsiveness to various materials including biopolymers.

Nanotechnology provides effective methods for precisely delivering chemotherapeutics to cancer cells, thereby improving efficacy and reducing off-target side effects. The targeted delivery of nanoscale chemotherapeutics is accomplished by two different approaches, namely the exploitation of leaky tumor vasculature (EPR effect) and the surface modification of nanoparticles (NPs) with various tumor-homing peptides, aptamers, oligonucleotides, and monoclonal antibodies (mAbs). Because of higher binding affinity and specificity, mAbs have received a lot of attention for the detection of selective cancer biomarkers and also for the treatment of various types of cancer. Antibody-conjugated nanoparticles (ACNPs) are an effective targeted therapy for the efficient delivery of chemotherapeutics specifically to the targeted cancer cells. ACNPs combine the benefits of NPs and mAbs to provide high drug loads at the tumor site with better selectivity and delivery efficiency. The mAbs on the NP surfaces recognize their specific receptors expressed on the target cells and release the chemotherapeutic agent in a controlled manner. Appropriately designed and synthesized ACNPs are essential to fully realize their therapeutic benefits. In blood stream, ACNPs instantly interact with biological molecules, and a protein corona is formed. Protein corona formation triggers an immune response and affects the targeting ability of the nanoformulation. In this review, we provide recent findings to highlight several antibody conjugation methods such as adsorption, covalent conjugation, and biotin-avidin interaction. This review also provides an overview of the many effects of the protein corona and the theranostic applications of ACNPs for the treatment of cancer., Competing Interests: The authors declare no competing interests., (Copyright © 2023, Kumari et al.)

Liver diseases are a leading cause of death worldwide and are rising exponentially due to increasing prevalence of metabolic disorders. Hepatic stellate cells (HSCs) are recognized as a key therapeutic target in liver diseases as these cells, upon activation during liver damage and ongoing liver inflammation, secrete excessive amounts of extracellular matrix that leads to liver tissue scarring (fibrosis) responsible for liver dysfunction (end-stage liver disease) and desmoplasia in hepatocellular carcinoma. Targeting of HSCs to reverse fibrosis progression has been realized by several experts in the field, including us. We have developed strategies to target activated HSCs by utilizing the receptors overexpressed on the surface of activated HSCs. One well-known receptor is platelet derived growth factor receptor-beta (PDGFR-β). Using PDGFR-β recognizing peptides (cyclic PPB or bicyclic PPB), we can deliver biologicals, e.g., interferon gamma (IFNγ) or IFNγ activity domain (mimetic IFNγ), to the activated HSCs that can inhibit their activation and reverse liver fibrosis. In this chapter, we provide the detailed methods and the principles involved in the synthesis of these targeted (mimetic) IFNγ constructs. These methods can be adapted for synthesizing constructs for targeted/cell-specific delivery of peptides/proteins, drugs, and imaging agents useful for various applications including diagnosis and treatment of inflammatory and fibrotic diseases and cancer., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Antibody–enzyme complexes (AECs) are ideal molecular recognition elements for immunosensing applications. One molecule possesses both a binding ability to specific targets and catalytic activity to gain signals, particularly oxidoreductases, which can be integrated into rapid and sensitive electrochemical measurements. The development of AECs using fragment antibodies rather than intact antibodies, such as immunoglobulin G (IgG), has attracted attention for overcoming the ethical and cost issues associated with the production of intact antibodies. Conventionally, chemical conjugation has been used to fabricate AECs; however, controlling stoichiometric conjugation using this method is difficult. To prepare homogeneous AECs, methods based on direct fusion and enzymatic conjugation have been developed, and more convenient methods using Catcher/Tag systems as coupling modules have been reported. In this review, we summarize the methods for fabricating AECs using fragment antibodies developed for sensing applications and discuss the advantages and disadvantages of each method. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS-CoV-2 and S. pneumoniae infection represents a long-sought "magic bullet". Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B-immunized serum not only broadly cross-neutralizes all SARS-CoV-2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS-CoV-2 mouse-adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide-RBD-conjugated nanoparticle vaccine platforms for the development of vaccines for COVID-19 and other infectious diseases., (© 2022 Wiley-VCH GmbH.)

Polysaccharides are abundant natural polymers, which in nature are at times covalently modified with peptides and proteins. Polysaccharide–protein or polysaccharide–peptide conjugates, natural or otherwise, may have increased solubility, improved emulsion properties, prolonged circulation time, reduced immunogenicity, and enhanced selectivity for targeting specific tissues compared to native peptides and proteins. In this paper, we will review recent advances in synthetic methods for producing polysaccharide–protein conjugates and discuss their advantages with a focus on drug targeting. [Display omitted] • Advances in chemical synthesis of polysaccharide-protein conjugates reviewed • Enhanced properties of polysaccharide-protein conjugates described • Challenges in synthetic methods discussed [ABSTRACT FROM AUTHOR]