Search Results (73)

Nanovaccines have emerged as a transformative platform in immunotherapy, distinguished by their capabilities in targeted antigen delivery, enhanced immunogenicity, and multifunctional integration. By leveraging nanocarriers, these vaccines achieve precise antigen transport, improve immune activation efficiency, and enable synergistic functions such as antigen protection and adjuvant co-delivery. This review comprehensively explores the foundational design principles of nanovaccines, delves into the diversity of nanovaccine design strategies—including the selection of primary carrier materials, functionalization modification, synergistic delivery of immune adjuvants, and self-assembled nano-delivery systems—and highlights their applications in cancer immunotherapy, infectious disease and autoimmune diseases. Furthermore, it critically examines existing technical challenges and translational barriers, providing an integrative reference to guide future research and development in this dynamic field. Full article

Veterinary vaccines are essential tools for controlling infectious and zoonotic diseases, safeguarding animal welfare, and ensuring global food security. However, conventional vaccines are hindered by cold-chain dependence, thermal instability, and logistical challenges, particularly in low- and middle-income countries (LMICs). This review explores next-generation veterinary vaccines, emphasizing innovations in thermostability and delivery platforms to overcome these barriers. Recent advances in vaccine drying technologies, such as lyophilization and spray drying, have improved antigen stability and storage resilience, facilitating effective immunization in remote settings. Additionally, novel delivery systems, including nanoparticle-based formulations, microneedles, and mucosal routes (intranasal, aerosol, and oral), enhance vaccine efficacy, targeting immune responses at mucosal surfaces while minimizing invasiveness and cost. These approaches reduce reliance on cold-chain logistics, improve vaccine uptake, and enable large-scale deployment in field conditions. The integration of thermostable formulations with innovative delivery technologies offers scalable solutions to immunize livestock and aquatic species against major pathogens. Moreover, these strategies contribute significantly to One Health objectives by mitigating zoonotic spillovers, reducing antibiotic reliance, and supporting sustainable development through improved animal productivity. The emerging role of artificial intelligence (AI) in vaccine design—facilitating epitope prediction, formulation optimization, and rapid diagnostics—further accelerates vaccine innovation, particularly in resource-constrained environments. Collectively, the convergence of thermostability, advanced delivery systems, and AI-driven tools represents a transformative shift in veterinary vaccinology, with profound implications for public health, food systems, and global pandemic preparedness. Full article

Background and Aim: Colorectal cancer remains a leading cause of cancer-related mortality, with growing interest in nanotechnology-driven immunotherapeutics. Gold nanoparticles (AuNPs) offer a promising platform due to their biocompatibility, functional versatility, and immunomodulatory potential. Carcinoembryonic antigens (CEAs), highly expressed in colorectal tumors, provide an ideal target for antigen-specific immune activation. The aim of this study is to evaluate the immunogenicity, biodistribution, and therapeutic efficacy of a CEA-functionalized gold nanoparticle (CEA-AuNP) construct in a mouse model of colorectal cancer following oral administration via a customized capsular delivery system. Methods: A 30-day oral administration study was performed in BALB/c mice (n = 30), who received increasing doses of CEA-AuNPs (5–50 mg/kg/day). Histological, hyperspectral imaging, and ELISA-based cytokine analyses were conducted to assess organ integrity, nanoparticle accumulation, and immune modulation. Results: CEA-AuNPs demonstrated a favorable safety profile and dose-dependent accumulation in reticuloendothelial tissues, particularly the spleen and liver. Cytokine profiling revealed enhanced IL-10 responses in the spleen, indicating anti-inflammatory immune modulation, with localized pro-inflammatory signals observed in hepatic tissue at higher doses. No signs of systemic toxicity or significant off-target effects were detected. Conclusions: The oral administration of CEA-AuNPs in healthy mice induced tissue-specific immune responses and exhibited a dose-dependent biodistribution pattern. These results support the further development of CEA-AuNPs as a nanovaccine platform for colorectal cancer immunoprophylaxis. Full article

Therapeutic vaccines offer a targeted approach to enhancing anti-tumor immunity with minimal systemic toxicity. Despite advancements in surgery, chemotherapy, radiation, and immunotherapy, colorectal cancer (CRC) remains a major clinical challenge, particularly due to the limited efficacy of immune checkpoint inhibitors outside the MSI-H subgroup. In this comprehensive review summarizes the emerging vaccine modalities for CRC, including peptide, nucleic acid, cell-based, vector-driven, and nanotechnology platforms. We discuss the barriers posed by tumor immune evasion and heterogeneity, and highlight innovative strategies designed to improve vaccine efficacy. Finally, we explore recent clinical developments and translational opportunities that position therapeutic vaccines as a promising component of future CRC immunotherapy. Full article

Background: African swine fever (ASF) is a highly contagious acute febrile disease with a near 100% mortality rate. There are currently no safe and effective vaccines for this disease. Cellular immunity plays an important role in the process of anti-viral, activating an effective cellular immune response is a prerequisite for the effectiveness of the vaccine. Methods: To effectively activate cellular immune responses, 133 immunodominant T cell epitopes (TEPs) were identified and synthesized into ten recombinant multi-epitope proteins (MEPs). These MEPs were subsequently conjugated to porcine ferritin (pFTH1) to generate MEPs-pFTH1 nanoparticles. Animal experiments were conducted to evaluate their immunogenicity and biocompatibility. Results: Animal experiments demonstrated that both MEPs and MEPs-pFTH1 nanoparticles induced significant humoral and cellular immune responses. Compared to MEPs monomers, the MEPs-pFTH1 nanoparticles induced a 10- to 100-fold increase in IgG and IgG2a antibody titers (p < 0.05), as well as a significantly higher number of IFN-γ⁺ cells. Serum from pigs immunized with MEPs-pFTH1 nanoparticles can significantly inhibit ASFV replication. Conclusions: Our novel self-assembled porcine ferritin nanovaccine candidate can induce strong humoral and cellular immune responses in swine and mice that effectively inhibit ASFV replication. Therefore, the nanovaccine is a highly biocompatible and safe candidate vaccine for ASF that warrants further investigation, such as conducting animal challenge experiments to evaluate the effectiveness of the vaccine. Full article

Background: A key component in modern vaccine development is the adjuvant, which enhances and/or modulates the antigen-specific immune response. In recent years, nanoparticle (NP)-based adjuvants have attracted much research attention owing to their ability to enhance vaccine potency. Nonetheless, how the selection of different antigens influences the overall vaccine efficacy when combined with the same nanoparticle adjuvant is less discussed, which is important for practical applications. Methods: Non-toxic mutants of exotoxin Hla (rHlaH35L) and cell-wall-anchored protein SpA(rSpam) were covalently conjugated to Poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) 25% NPs (25% NPs) as antigens to prepare nanovaccines. Antibody titers, cytokine secretion levels, and the antibody bacteriolytic capacity were tested to investigate immune activation. To evaluate the protective efficacy of the nanovaccine, immunized mice were challenged with S. aureus ATCC 25923 at three different lethal doses: 1 × LD₁₀₀, 2 × LD₁₀₀, and 4 × LD₁₀₀. Results: We showed that 25% NP-rHlaH35L nanovaccines were associated with more efficient humoral, cellular, and innate immune responses and protection potency compared with 25% NP-rSpam. Moreover, the overall vaccine potency of 25% NP-rHlaH35L was even better than the combination vaccination of both 25% NP-rHlaH35L and 25% NP-rSpam. In comparison to the clinically used aluminum (alum) adjuvant, the 25% NP adjuvants were found to stimulate humoral and cellular immune responses efficiently, irrespective of the antigen type. For antigens, either exotoxins or cell-wall-anchored proteins, the 25% NP-based vaccines show excellent protection for mice from S. aureus infection with survival rates of 100% after lethal challenge, which is significantly superior to the clinically used alum adjuvant. Moreover, due to the superior immune response elicited by 25% NP-rHlaH35L, the animals inoculated with this formulation survived even after two times the lethal dose of S. aureus administration. Conclusions: We demonstrated that the type of antigen plays a key role in determining the overall vaccine efficacy in the immune system when different kinds of antigens are conjugated with a specific nanoparticle adjuvant, paving a new way for vaccine design based on 25% NP adjuvants with enhanced potency and reduced side effects. Full article

Background/Objectives: Immunotherapy has shown promising results in some cancers, but its efficacy remains limited in pancreatic ductal adenocarcinoma (PDAC). Vaccines in nanoparticle form (nanovaccines) can incorporate immunostimulating components to induce a potent immune response. As mesothelin (MSLN) is a tumor-associated antigen overexpressed in PDAC, we evaluated the effect of MSLN nanovaccine in a syngeneic orthotopic KPC-PDAC mouse model. Methods: An MSLN peptide combining three MSLN epitopes and two adjuvants, poly I:C and R848, was encapsulated in PLGA–chitosan nanoparticles to generate the nanovaccine. Results: The MSLN nanovaccine was successfully taken up by dendritic cells in vitro and was found in inguinal lymph nodes 24 h after subcutaneous injection into C57BL/6 mice. Nanovaccine re-stimulation of splenocytes from vaccinated mice led to increased levels of interferon-γ in vitro compared to unstimulated splenocytes. Higher levels of MSLN-specific IgM and IgG antibodies were detected in the serum of vaccinated mice compared to that of control mice. Three vaccination regimens were tested: a prophylactic scheme that included vaccination before tumor induction and two therapeutic schemes involving early and late vaccination after tumor cell inoculation. MSLN nanovaccination inhibited KPC tumor progression and metastasis and induced higher CD8⁺ T cell infiltration in the tumor that developed in response to prophylactic and early therapeutic schedules but not in response to a later vaccination approach. Although the nanovaccine treatment elicited higher humoral and cellular antigen-specific responses in tumor-bearing mice for both vaccination strategies, the therapeutic vaccination also increased the expression of exhaustion markers in CD8⁺ T cells. Conclusions: Our results support the relevance of an MSLN-based nanovaccine as a new immunotherapy treatment for PDAC and propose an innovative method of vaccine delivery using NPs. Full article

Cancer is one of the leading causes of morbidity and mortality globally, responsible for approximately 10 million deaths in 2022 and an estimated 21 million new cases in 2024. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy often present limitations in efficacy and side effects. However, immunotherapeutic vaccines have emerged as a promising approach, leveraging the body’s immune system to target and eliminate cancer cells. This review examines the evolving landscape of cancer vaccines, differentiating between preventive and therapeutic strategies and highlighting the significance of tumor-specific antigens, including tumor-associated antigens (TAAs) and neoantigens. Recent advancements in vaccine technology, particularly through nanotechnology, have resulted in the development of nanovaccines, which enhance antigen stability, optimize delivery to immune cells, and promote robust immune responses. Notably, clinical data indicate that patients receiving immune checkpoint inhibitors can achieve overall survival rates of approximately 34.8 months compared to just 15.7 months for traditional therapies. Despite these advancements, challenges remain, such as the immunosuppressive tumor microenvironment and tumor heterogeneity. Emerging evidence suggests that combining nanovaccines with immunomodulators may enhance therapeutic efficacy by overcoming these obstacles. Continued research and interdisciplinary collaboration will be essential to fully exploit the promise of nanovaccines, ultimately leading to more effective and accessible treatments for cancer patients. The future of cancer immunotherapy appears increasingly hopeful as these innovative strategies pave the way for enhanced patient outcomes and an improved quality of life in oncology. Full article

Background/Objectives: Nanovaccines have significant potential to enhance immunization strategies by improving efficacy, safety, and cost-effectiveness. In particular, organic nanoparticles hold promise for the generation of low-cost nanovaccines obtained by environmentally friendly methods. In this study, the feasibility of using zein nanoparticles (NPs) as carriers for an antigenic peptide (p30) and the receptor binding domain (RBD) from SARS-CoV-2 spike protein was explored. Methods: A synthesis method for zein NPs was established by combining previously reported techniques, and the resulting NPs were characterized in terms of morphology, particle size, polydispersity index (PDI), surface charge, and colloidal stability using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Tween 20 was employed as a surfactant to enhance particle stability and prevent aggregation. Results: The zein NPs were deemed safe based on an in vitro cytotoxicity assay using Vero cells. Immunogenicity assessments demonstrated that zein NPs:p30 and zein NPs:RBD induced IgG responses in test mice, whose magnitude was comparable to those achieved with alum as an adjuvant. Conclusions: These findings support the use of zein NPs as promising vaccine delivery vehicles with adjuvant effects due to their ease and environmentally friendly synthesis, high stability, and low cost. Full article

Infectious diseases continue to pose a significant global health threat. To combat these challenges, innovative vaccine technologies are urgently needed. Nanoparticles (NPs) have unique properties and have emerged as a promising platform for developing next-generation vaccines. Nanoparticles are revolutionizing the field of vaccine development, offering a new era of immunization. They allow the creation of more effective, stable, and easily deliverable vaccines. Various types of NPs, including lipid, polymeric, metal, and virus-like particles, can be employed to encapsulate and deliver vaccine components, such as mRNA or protein antigens. These NPs protect antigens from degradation, target them to specific immune cells, and enhance antigen presentation, leading to robust and durable immune responses. Additionally, NPs can simultaneously deliver multiple vaccine components, including antigens, and adjuvants, in a single formulation, simplifying vaccine production and administration. Nanovaccines offer a promising approach to combat food- and water-borne bacterial diseases, surpassing traditional formulations. Further research is needed to address the global burden of these infections. This review highlights the potential of NPs to revolutionize vaccine platforms. We explore their mechanisms of action, current applications, and emerging trends. The review discusses the limitations of nanovaccines, innovative solutions and the potential role of artificial intelligence in developing more effective and accessible nanovaccines to combat infectious diseases. Full article

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. Full article

Background: The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections. Methods: In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (Soc⁻Hoc⁻T4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens. Results: The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4⁺ and CD8⁺ T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy. Conclusions: In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza. Full article

Background/Objectives: Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T_RM) cells and tissue-resident memory B (B_RM) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses. However, the interactions between RSV vaccines and mucosal immune responses within the respiratory tract are poorly understood. We evaluated a mucosal immune system following immunization by RSV vaccine with poly-sorbitol transporter (RSV-PST), a nanoparticle adjuvant. Methods: We intranasally immunized the RSV-PST and identified the systemic and mucosal immune responses. Furthermore, we challenged with RSV A2 strain after immunization and investigated the protective effects. Results: Consequently, antigen-specific CD8⁺ T_RM cells were markedly elevated in the lung parenchyma, yet exhibited impaired cytokine expression. In contrast, humoral immunity, with systemic antibody production from serum, but not in the respiratory tract, was significantly increased by RSV-PST immunization. Interestingly, the production of respiratory mucosal antigen-specific IgG after RSV A2 challenge dramatically increased in the bronchoalveolar lavage fluid (BALF) of the RSV-PST immunized group in the presence of FTY720, and the lung-infected RSV titer was significantly lower in this group. Furthermore, after RSV A2 challenge, CD69⁺ IgG⁺ B_RM cells were significantly increased in lung tissues in the RSV-PST group. Conclusions: The RSV-PST vaccine has protective effects against RSV infection by promoting both systemic and local humoral immunity rather than cellular immunity. Full article

The development of effective vaccines necessitates a delicate balance between maximizing immunogenicity and minimizing safety concerns. Subunit vaccines, while generally considered safe, often fail to elicit robust and durable immune responses. Nanotechnology presents a promising approach to address this dilemma, enabling subunit antigens to mimic critical aspects of native pathogens, such as nanoscale dimensions, geometry, and highly repetitive antigen display. Various expression systems, including Escherichia coli (E. coli), yeast, baculovirus/insect cells, and Chinese hamster ovary (CHO) cells, have been explored for the production of nanoparticle vaccines. Among these, E. coli stands out due to its cost-effectiveness, scalability, rapid production cycle, and high yields. However, the E. coli manufacturing platform faces challenges related to its unfavorable redox environment for disulfide bond formation, lack of post-translational modifications, and difficulties in achieving proper protein folding. This review focuses on molecular and protein engineering strategies to enhance protein solubility in E. coli and facilitate the in vitro reassembly of virus-like particles (VLPs). We also discuss approaches for antigen display on nanocarrier surfaces and methods to stabilize these carriers. These bioengineering approaches, in combination with advanced nanocarrier design, hold significant potential for developing highly effective and affordable E. coli-derived nanovaccines, paving the way for improved protection against a wide range of infectious diseases. Full article

Cationic vaccines of nanometric sizes can directly perform the delivery of antigen(s) and immunomodulator(s) to dendritic cells in the lymph nodes. The positively charged nanovaccines are taken up by antigen-presenting cells (APCs) of the lymphatic system often originating the cellular immunological defense required to fight intracellular microbial infections and the proliferation of cancers. Cationic molecules imparting the positive charges to nanovaccines exhibit a dose-dependent toxicity which needs to be systematically addressed. Against the coronavirus, mRNA cationic nanovaccines evolved rapidly. Nowadays cationic nanovaccines have been formulated against several infections with the advantage of cationic compounds granting protection of nucleic acids in vivo against biodegradation by nucleases. Up to the threshold concentration of cationic molecules for nanovaccine delivery, cationic nanovaccines perform well eliciting the desired Th 1 improved immune response in the absence of cytotoxicity. A second strategy in the literature involves dilution of cationic components in biocompatible polymeric matrixes. Polymeric nanoparticles incorporating cationic molecules at reduced concentrations for the cationic component often result in an absence of toxic effects. The progress in vaccinology against cancer involves in situ designs for cationic nanovaccines. The lysis of transformed cancer cells releases several tumoral antigens, which in the presence of cationic nanoadjuvants can be systemically presented for the prevention of metastatic cancer. In addition, these local cationic nanovaccines allow immunotherapeutic tumor treatment. Full article