Search Results (231)

Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine with improved safety profiles would have significant clinical and public health implications. Methods: Building upon our previously optimized truncated gE (tgE350) from VZV, we developed the tgE350 + Fe nanoparticle vaccine using SpyTag/SpyCatcher covalent conjugation. The tgE350 protein (with a SpyTag tag) and the Fe protein (with a SpyCatcher tag) were expressed in HEK293F and E. coli BL21, respectively, enabling spontaneous nanoparticle assembly. Protein expression and nanoparticle formation were confirmed through SDS-PAGE and negative-stain electron microscopy. BALB/c mice were inoculated with either tgE350 + Fe or tgE350 combined with Al and CpG adjuvants. Immune responses were evaluated using ELISpot and flow cytometry for cellular immunity, along with ELISA, VZV microneutralization, and fluorescent antibody membrane antigen (FAMA) assays for antibody titers. Histopathological examination of major organs ensured vaccine safety. Results: Compared with the truncated vaccine tgE350, the nanoparticle vaccine tgE350 + Fe significantly enhanced VZV neutralizing antibodies and specific antibody responses in mice without causing significant changes in lymphocyte populations (no difference from the control group). Moreover, the tgE350 + Fe group had significantly more lymphocytes secreting IFN-γ, IL-2, and IL-4 than the tgE350 group. No apparent pathological damage was observed in the heart, liver, spleen, or lungs of mice in any experimental group. Conclusions: This experiment successfully developed the HZ nanoparticle vaccine tgE350 + Fe. It enhanced VZV-specific neutralizing antibodies, generated better cellular and humoral immune responses, and demonstrated good safety. Full article

Therapeutic peptides have rapidly evolved into multifunctional tools for precision oncology, offering molecular specificity and biocompatibility. Their roles in cancer therapy, however, are inherently overlapping. The same peptide can function as a targeting ligand, a cell-penetrating motif, a therapeutic effector, or a structural component of peptide–drug conjugates (PDCs), nanoparticle (NP) systems, and radionuclide constructs. This functional convergence makes rigid classification challenging. In this review, we therefore organize peptide modalities according to their dominant therapeutic function while acknowledging the fluid boundaries between categories. Firstly, we outline the main functional classes of therapeutic peptides, covering their use as targeting ligands and their roles as active agents (i.e., receptor agonists/antagonists, intracellular protein–protein interaction modulators, etc.). Additionally, we summarize their application in peptide–drug conjugates (PDCs), peptide-guided radionuclides, and cancer vaccines, integrating key mechanistic principles and clinical evidence. Finally, we discuss the major translational barriers to clinical use and how they might be overcome. The developments in peptide engineering position them as adaptable, multifunctional platforms capable of improving precision, reducing toxicity, and advancing personalized cancer care. Full article

This study evaluated the formulation and stability of a quadrivalent glycoconjugate Shigella vaccine candidate based on four predominant strains (S. flexneri; 2a, 3a, and 6, and S. sonnei) covering ~64% of global Shigella infections. Each glycoconjugate antigen consists of a strain-specific O-polysaccharide (O-PS) covalently linked to the carrier protein IpaB, a component of the Shigella type III secretion system. First, selective competitive ELISAs were developed to measure antigenicity of the four O-PS-IpaB conjugates formulated with different adjuvants (i.e., Alhydrogel^®, AH; Adju-phos^®, AP; and CpG-1018^®, CpG). Next, the monovalent S. sonnei O-PS-IpaB conjugate was studied to elucidate interactions with aluminum salt adjuvants (AH, AP) under different solution conditions. Third, the stability profiles of AH- or AP-adjuvanted S. sonnei O-PS-IpaB conjugate in various formulations (±CpG) were determined at different temperatures. Interestingly, incubation at 25 °C for 2 weeks resulted in increased antigenicity values when the antigen was bound to AP or AH, suggesting increased epitope exposure upon adjuvant binding. When bound to AP adjuvant at pH 5.8, the best glycoconjugate antigen stability was observed at elevated temperatures. The CpG adjuvant under these conditions, however, displayed incompatibility (i.e., material loss), presumably from precipitation due to lack of interaction with AP and presence of the detergent LDAO from the bulk antigen buffer. In contrast, the glycoconjugate antigen and CpG adjuvant were both bound to the AH adjuvant and stable at 2–8 °C, pH 7.0. This AH-CpG formulation of the O-PS-IpaB conjugate antigens was identified as a promising candidate for future animal immunogenicity testing. Full article

Streptococcus pneumoniae contributes significantly to morbidity, mortality, and healthcare costs worldwide due to severe Invasive Pneumococcal Disease (IPD), particularly among young children and vulnerable populations. This review critically examines the current state of pneumococcal disease epidemiology, the evolution of vaccine strategies, and persistent challenges to achieve global control of the disease. The implementation of Pneumococcal Conjugate Vaccines (PCVs) has yielded substantial public health gains, establishing herd protection and sharply reducing vaccine-type IPD incidence. However, this success has been fundamentally challenged by serotype replacement, where non-vaccine serotypes have subsequently emerged to cause a significant proportion of the residual disease burden. This epidemiological shift has necessitated the development and deployment of higher-valency PCVs (PCV15, PCV20, and PCV21) to expand serotype coverage. Furthermore, optimal protection requires personalized strategies for high-risk cohorts where vaccine effectiveness can be compromised. In this context, the review details how pneumococcal vaccination—and particularly PPSV23—serves as an indispensable diagnostic tool to evaluate a broad spectrum of Inborn Errors of Immunity (IEI) and in particular humoral defects. Diagnostic challenges are strained by non-standardized assays and the limited panel of unique serotypes available for testing in the PCV era. The scientific priority is now the development of universal protein-based vaccines, to provide protection against all serotypes and non-encapsulated strains by targeting conserved virulence factors. This integrated approach, combining expanded PCV coverage with novel vaccine technology, is essential to mitigate the ongoing public health burden of pneumococcal disease. Full article

Backgroud/Objectives: Canine Visceral Leishmaniasis (CVL), caused by Leishmania infantum, is a significant public health concern due to dogs serving as reservoirs for human infection. An accurate and rapid diagnostic method to distinguish symptomatic and asymptomatic CVL from healthy and vaccinated animals is essential for controlling canine and human disease. Developing innovative antibody detection techniques and exploring new antigens are essential for enhancing CVL testing efficiency. Our study focuses on a multiplex flow cytometry technique to detect Leishmania-specific antibodies in canine serum. This involved conjugating small peptides with carrier proteins or peptide tags, sequences designed to facilitate bead coupling. Methods: A peptide from the L. infantum A2 protein was coupled to beads in three forms: unconjugated, conjugated with BSA, and conjugated with a C-terminal β-alanine–lysine (x4)–cysteine TAG. This TAG was previously designed to enhance peptide solubility, improve binding efficiency, and provide functional groups for covalent attachment to the beads, ensuring stable immobilization in the multiplex assay. Results: Our results suggest that the multiplex approach shows promise as a rapid serological test for CVL, particularly with TAG-conjugated peptides, which optimize bead coupling. However, peptide/BSA conjugation revealed anti-BSA antibodies in samples from healthy and CVL dogs. Conclusions: In conclusion, our findings highlight the potential of multiplex methodologies to enhance CVL diagnostics and caution against using BSA as a bead coupling agent in serological tests for canine samples due to its impact on test specificity and sensitivity. Full article

Background: The development of an effective HIV-1 vaccine remains a major challenge due to HIV-1’s extraordinary diversity, high mutation rate, and the rarity of broadly neutralizing antibody (bnAb) precursors. To address these challenges, we have previously immunized rabbits with mRNA-LNPs encoding for HIV-1 envelope glycoproteins (Envs), together with mRNA-LNPs encoding for HIV-1 Gag, which likely mediated the generation of virus-like particles presenting HIV-1 Envs to the immune system in vivo. Methods: Here, we investigated whether an escalating dose (ED) immunization using mRNA-LNP priming, followed by boosts with synthetic, protein-based, virus-like particles (synVLPs) displaying HIV-1 SOSIP trimers via SpyTag/SpyCatcher conjugation (group 1), could improve the quality and durability of the antibody responses compared to conventional bolus immunization (group 2). Previous studies have shown that, in contrast to single bolus immunization, the ED priming strategy could enhance B cell activation and prolong affinity maturation, resulting in higher-quality antibody responses. Results: Upon vaccination, rabbits from both groups developed strong homologous anti-Env antibody responses, with an increasing ability of sera from immunized rabbits to bind Envs following subsequent boosts. Antibodies in rabbit sera bound heterologous Envs, but there was no statistically significant difference in binding between the two groups. Overall, antibody responses were comparable across all animals and declined similarly over time in both groups, indicating that neither the adjuvants nor the ED priming led to any marked differences within this small sample size. Neutralization activity against homologous tier-2 HIV-1_AD8 (mRNA prime) and tier-2 HIV-1₁₀₅₉ (protein boost) was generally low across both groups; however, a higher neutralization titer was observed for the ED group against HIV-1_AD8 following the final boost. One of the rabbits from the bolus group exhibited exceptionally high neutralization titers that correlated with elevated Env-specific binding against HIV-1₁₀₅₉. Conclusions: These results highlight the challenges in eliciting broad and potent neutralizing antibody (nAb) responses. Our findings underscore the need for the continued development and refinement of immunogen design and delivery strategies to guide the elicitation of nAb. Full article

Background: The immunogenicity of polysaccharide conjugate vaccines is critically influenced by the choice of carrier protein, which promotes a T-cell-dependent immune response mechanism leading to strong antibody production. In this study, the cholera toxin B subunit (CTB), a non-toxic pentameric protein, was evaluated as a novel carrier protein for pneumococcal polysaccharide antigens. Methods: Recombinant CTB was produced in Escherichia coli and purified using scalable chromatographic methods. Pneumococcal polysaccharides from serotypes 7F, 22F, and 33F were chemically activated with CDAP and conjugated to CTB. Results: The resulting glycoconjugates were characterized by SEC-MALS, confirming successful conjugation, high molecular weights, consistent polysaccharide-to-protein ratios, and acceptable endotoxin levels. Immunogenicity was assessed in rabbits following immunization with alum-adjuvanted formulations. Conclusions: Robust IgG responses were elicited by all CTB-based conjugates, with antibody levels found to be comparable to those induced by CRM197 conjugates, demonstrating the potential of CTB as a promising alternative for the next generation of conjugate vaccines. Full article

The recent SARS-CoV-2 pandemic has highlighted the need for quickly adaptable technologies in vaccine manufacturing. This can be achieved through virus-like particles (VLPs) as presentation platforms for target antigens. In this study, we investigated the purification of VLPs of the Hepatitis B Core antigen (HBc) and the SplitCore (SplCo) technology. The outer surface protein C (OspC) of Borrelia burgdorferi was genetically fused to HBc and its N-terminal SplCo protein. Product solubility in E. coli increased from 40% for HBc-OspC to 90% for SplCo-OspC. This could not be reproduced with similar SARS-CoV-2 receptor-binding domain fusions due to inclusion body formation. Hydrophobicity was found to be significantly lowered for the OspC fusions, in particular for the SplCo variant. Pre-purified samples were generated by precipitating soluble cell lysate. Subsequently, solubilized precipitates were subjected to anion exchange chromatography (AEX), and the elution fractions obtained contained VLPs, albeit with low purity. The VLPs were also disassembled prior to AEX for dissociative purification, but a subsequent reassembly could not be achieved for both fusion variants. A novel HBc variant was constructed for post-translational modification via click-chemistry. The solubility and hydrophobicity of this HBc variant remained high, but native AEX resulted in complete product loss. By contrast, a yield of 84% VLPs was obtained for the modified HBc after dissociative AEX. The surface-exposed azide group on the particles, introduced for click-chemistry, enabled coupling to fluorophores without compromising VLP stability. Conjugation efficiencies of up to 59% were obtained. These results suggest the potential of combining HBc and click-chemistry for future applications, e.g., the presentation of immunogenic epitopes or antigens. This underlines that for every antigen, both the optimal scaffold-decoration strategy and the subsequent manufacturing process should be carefully selected. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of infectious disease mortality worldwide. Global TB control efforts face several hurdles, including the lack of a broadly effective vaccine, limited sensitivity of current diagnostics, particularly for paucibacillary and extrapulmonary TB, and significant adverse effects associated with prolonged small-molecule drug regimens. The growing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains further underscores the urgent need for innovative therapeutic strategies. We outline characteristics of next-generation TB therapeutics. We show that antibody (Ab)-drug conjugates (ADCs) satisfy many of those desirable characteristics. Since a major hurdle to this approach lies in Mtb-specific Abs, we highlight an open-access resource comprising a broad panel of Mtb-specific mouse monoclonal antibodies targeting key factors involved in Mtb survival, immune evasion, and pathogenesis. These critical Mtb virulence factors include heat shock proteins (GroES, DnaK, and HspX), surface-associated or secreted proteins (LAM, Ag85, HBHA, Mpt64/CFP-21, and PhoS1/PstS1), cell wall/envelope-associated proteins (LprG/p27), and detoxifying enzymes (KatG and SodA). The resource provides full-length sequences of the immunoglobulin variable regions, enabling antibody engineering and facilitating translational TB research across vaccine design, diagnostic development, and immunotherapeutic applications, in addition to ADCs. This ADC targeted delivery strategy holds promise for overcoming TB heterogeneity and eliminating both active and dormant Mtb populations within a single therapeutic formulation and offers a novel avenue for precision TB treatment. Full article

Background/Objectives: Group B Streptococcus (GBS) is a significant cause of perinatal infection in neonates and infants. Complications could include neonatal sepsis and meningitis, preterm birth, stillbirth, or death. Though no GBS vaccine is currently licensed, maternal immunization is expected to be a highly effective strategy to address invasive GBS disease—particularly in low- and middle-income countries (LMICs), where the disease burden is the greatest and access to existing interventions is limited. In this study, we present a novel hexavalent GBS vaccine candidate with a unique combination of serotypes (ST)—Ia, Ib, II, III, V, and VII—that could be an efficacious and cost-effective intervention, with the broadest coverage of 99% against circulating serotypes globally. Methods: The 6-valent conjugate vaccine candidate, GBS-06, is developed using a novel approach by linking the six polysaccharides (PS) to recombinant cross-reactive material 197 (rCRM197) carrier protein derivatized with a hydrazide-polyethylene glycol-hydrazide (HZ-PEG-HZ) linker. A repeat-dose GLP toxicology study with GBS-06 was conducted at the highest clinical dose of 20 µg in rabbits with saline as the placebo control. Results: The results reveal induction of robust anti-capsular polysaccharide-specific IgG responses against each of the six serotypes after each dose with the highest antibody GMCs at Day 49 following the third dose. Conclusions: Hence, this work is the first demonstration of strong immunogenicity achieved using a linker (HZ-PEG-HZ) for GBS glycoconjugate vaccine development. The positive data from the study have strong implications in the advancement of the candidate for evaluation in clinical trials and provide a licensure pathway for maternal immunization. Full article

Elite athletes are at an increased risk of infections due to behavioral and social factors and frequent travel. Furthermore, heavy physical exercise may induce immunosuppression. Most infections in athletes are acute respiratory illnesses (ARIs) with various viral etiologies. Although athletes, as young, healthy adults, are not at risk for severe infections, a prolonged ARI may ruin a training season or a significant competition or may spread within a sports team. Many common infections are vaccine-preventable. This Opinion advocates for more active vaccination among athletes, although some of the vaccines are not officially recommended for young adults. New respiratory syncytial virus (RSV) protein vaccines are effective and well-tolerated. Yearly influenza and COVID-19 vaccinations are strongly recommended. Conjugated polyvalent pneumococcal vaccines are recommended because they may also induce protection against respiratory viral infections. Pertussis and measles outbreaks are occurring globally. The history of measles vaccination should be reviewed, and consideration should be given to a pertussis booster vaccination (Tdap). A recombinant vaccine can effectively prevent herpes zoster. The vaccination of elite athletes is a cost-effective and powerful tool, but it is currently underused. The sports medicine community can address vaccine hesitancy among athletes by listening to their concerns and giving accurate information. Full article

Chronic pain affects millions of individuals globally and continues to pose a major burden on patients and healthcare systems. Traditional analgesics, such as opioids and nonsteroidal anti-inflammatory drugs, often provide only partial relief and are frequently associated with significant side effects and risks of misuse. In recent years, vaccines that target molecules involved in pain signaling have emerged as an innovative therapeutic strategy. These vaccines aim to induce long-lasting immune responses against key mediators of nociception, including nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), substance P, and voltage-gated sodium channels such as Nav1.7. By promoting the production of specific antibodies, anti-pain vaccines have the potential to achieve analgesic effects with longer duration, reduced need for frequent administration, and improved accessibility. Multiple vaccine platforms are under investigation, including virus-like particles, peptide-protein conjugates, and nucleic acid technologies. Although preclinical studies have shown promising efficacy and safety profiles, clinical evidence is still limited to early-stage trials, particularly for migraine. This narrative review summarizes current knowledge on therapeutic vaccines for pain, discusses the immunological and technological advances in the field, and outlines future directions. Full article

Nasopharyngeal carcinoma (NPC) is a rare malignancy with a distinct epidemiological pattern and is most often associated with Epstein–Barr virus (EBV). EBV plays a critical role in NPC pathogenesis, with viral proteins driving oncogenesis by altering immune regulation, apoptosis, and tumor progression. The unique molecular landscape of NPC presents both challenges and opportunities for therapeutic development, particularly in the recurrent and metastatic (R/M) setting, where treatment resistance remains a major hurdle. While platinum-based chemotherapy has traditionally been the standard of care for R/M NPC, immune checkpoint inhibitors (ICIs) have emerged as a key component of treatment. However, both intrinsic and acquired resistance to PD-1/PD-L1 blockade underscore the need for alternative strategies, including modulation of alternative immune checkpoints and simultaneous engagement of non-redundant pathways to enhance responses and durability. Leveraging EBV-driven biology, emerging immunotherapeutic approaches, such as EBV-specific adoptive cellular therapies and therapeutic vaccines, aim to induce durable immunity to viral proteins. Additionally, targeted therapies including receptor tyrosine kinase inhibitors, epigenetic modulators, and antibody–drug conjugates are redefining precision medicine by selectively delivering cytotoxic agents to tumors. With growing insights into the biology of NPC and evolving therapeutics, the integration of immunotherapy, targeted agents, and biomarker-driven strategies is poised to transform NPC treatment, emphasizing biology-driven, multimodal approaches to optimize patient outcomes. Full article

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration. Full article

Group A Streptococcus (GAS) imposes a significant global health burden across all age groups, annually causing over 600 million cases of pharyngitis and more than 18 million severe invasive infections or sequelae. The resurgence of scarlet fever globally and streptococcal toxic shock syndrome (STSS) outbreaks in Japan have brought GAS infections back into the spotlight as a pressing global health concern. Unfortunately, no licensed vaccine against GAS is yet available for clinical use. Our comprehensive review examines the developmental history of GAS vaccines, outlining the research trajectory from early inactivated vaccines to contemporary multivalent, conjugate, multi-antigen, and mRNA-based vaccine platforms. It systematically analyzes clinical trial outcomes of GAS vaccines, highlighting recent advances in both M protein-based and non-M protein vaccine candidates while summarizing promising target antigens. The review concludes with critical strategies to accelerate vaccine commercialization, including enhanced investment in research and development, expanded collaborations, leveraging advanced vaccine technologies, streamlined clinical trials, and strengthened public health advocacy. This review critically evaluates the current evidence and future prospects in GAS vaccine development, emphasizing innovative strategies and engaging broader stakeholders to accelerate GAS vaccine development. Full article