IMMUNOLOGIC RESEARCH
·
2023
·Vol. 71
·期 3
·356-372
·
IF 4.4
Lamprinou Malamatenia,Sachinidis Athanasios,Stamoula Eleni,Vavilis Theofanis,Papazisis Georgios
COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell’s palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.
研究领域:
免疫学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Egyptian Journal of Internal Medicine
·
2023
·Vol. 35
·期 1
·1-9
·
IF 0
Muslim Shahnawaz,Mustafa Gulam,Nasrin Nasrin,Firdaus Aaisha,Singh Shambhu Kumar
SARS-CoV-2, the causative agent of COVID-19, claimed multiple lives in a very short span of time. Seeing the urgency of situation, vaccines were developed in hitherto unseen time frame. Vaccines definitely passed the test of safety and efficacy in clinical trials, but post mass vaccination data revealed cases of fatal adverse conditions in the temporal association of vaccination. The temporal association does not guarantee that the fatality is due to vaccination, but at the same time, it does create a concern. To overcome this concern and improve the safety of vaccination, we reviewed literature and collected data of 15 studies comprising of total 22 cases of fatal adverse condition/death in the temporal association of COVID-19 vaccination. Analysis of these data shows that many persons (40.90%) who succumbed were previously healthy individuals. All those who died developed symptoms or were admitted to hospital within a period of 3 weeks after vaccination. 86.36% cases of death took place within a period of 3 weeks after vaccination/presentation/admission/intervention. Complications which lead to death were CVST, thrombocytopenia/thrombosis /VITT, DIC and haemorrhage in 81.18% of cases. 81.81% cases of death were noted in the temporal association with ChAdOx1 nCoV-19 vaccine. 68.18% persons developed symptoms after first dose. Death was more common in females (59.09%), and the most commonly affected age group was 20 to 60 years (86.36%). Knowledge of fatal adverse conditions in the temporal association of vaccination will help to tackle these situations well and improve the safety of vaccination drive further.
研究领域:
免疫学
·
流行病学
·
公共卫生
·
药理学
·
转化医学
✓ 已验证
DOI
ACS Nano
·
2025
·
IF 16
Jiamin Deng,Zongmei Wang,Liqin Wu,Zhiyong Song,Hagar Shendy Bahlol,Xun Li,Ling Zhao,Heyou Han
Rabies, caused by rabies virus (RABV), is a zoonotic disease with a high mortality rate that has attracted global attention with the goal of eradication by 2030. However, rabies can only be prevented by appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its high expenditure. Designing single-dose vaccines is a pressing challenge in the prevention of rabies and other infectious diseases. Herein, a metal–phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed to stimulate potent humoral immunity against RABV infection by a single immunization, resulting in 4.3-fold and 1.8-fold enhancements of virus-neutralizing antibody compared with that induced by inactivated RABV and alum adjuvant. The CGMR, cross-linked by phenol-modified chitosan with manganese ion, could prolong residence time by confining the antigen to the network of hydrogel, acting as a “hydrogel antigen depot”. It also stimulated the activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway, facilitating dendritic cell maturation and antigen presentation. The vaccine formulation recruited immunocytes and activated the germinal center, enhancing and sustaining humoral immune responses against the virulent RABV challenge. Collectively, this injectable manganese-based hydrogel vaccine provides a universal and ideal avenue for rabies and other infectious diseases.
研究领域:
免疫学
·
生物医学工程
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Reports Medicine
·
2025
·
IF 10.6
Cheng Gao,Ruifeng Luo,Cheryl H.T. Kwong,Jinwei Liu,Mian Tang,Beibei Xie,Tianshun Duan,Ruibing Wang
The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the “eat me” signals and inhibit the “don’t eat me” signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4 + T cells toward a T H 1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.
研究领域:
肿瘤学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Mengfei Li,Xue Zheng,Xinyang Yu,Shaolong Qi,Shoujun Zhu,Guocan Yu,Songling Zhang
mRNA vaccines have been widely implemented and revolutionized the landscape of oncology and epidemiology. Potent vaccination demands precise control over injection depth to ensure optimal lymphatic drainage, driving the development of non-invasive imaging techniques to visualize the distribution and efficacy of mRNA vaccines. Herein, near-infrared-II (NIR-II) lipid nanoparticles (NIR-II-LNPs) are fabricated for mRNA delivery by integrating a cationic fluorophore amphiphile (IR780-C16) into traditional LNPs, enabling longitudinal, quantitative, and non-invasive trafficking of mRNA vaccines. The in vivo behaviors of mRNA vaccines are characterized with different vaccination protocols in mice and rabbits by NIR-II fluorescence imaging. Results proved that following a 25 µL injection of mRNA vaccines into the mouse thigh at a depth of 4 mm or a 500 µL injection volume into a rabbit at a depth of 7 mm via the intramuscular route, the vaccines rapidly and abundantly accumulated in the inguinal lymph nodes. Flow cytometry and tissue immunofluorescence analyses further validated that optimized vaccination parameters effectively activated antitumor immunity and greatly boosted the therapeutic efficacy in B16-OVA and HPV-associated mouse tumor models. NIR-II-LNPs offer a unique modality for non-invasively monitoring the fate of vaccines, reinforcing its role in preclinical and clinical mRNA therapeutics.
研究领域:
肿瘤学
·
免疫学
·
生物医学工程
·
分子成像
·
疫苗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Emerging Microbes & Infections
·
2023
·
IF 13.2
Shuaijie Song,Shuyi Wang,Xiaoyun Jiang,Fan Yang,Shuai Gao,Xu’ai Lin,Hao Cheng,Stijn van der Veen
Global dissemination of high-level ceftriaxone-resistant Neisseria gonorrhoeae strains associated with the FC428 clone poses a threat to the efficacy ceftriaxone-based therapies. Vaccination is the best strategy to contain multidrug-resistant infections. In this study, we investigated the efficacy of MtrE and its surface Loop2 as vaccine antigens when combined with a Th1-polarizing adjuvant, which is expected to be beneficial for gonococcal vaccine development. Using in vitro dendritic cell maturation and T cell differentiation assays, CpG1826 was identified as the optimal Th1-polarizing adjuvant for MtrE and Loop2 displayed as linear epitope (Nloop2) or structural epitope (Intraloop2) on a carrier protein. Loop2-based antigens raised strongly Th1-polarized and bactericidal antibody responses in vaccinated mice. Furthermore, the vaccine formulations provided protection against a gonococcal challenge in mouse vaginal tract infection model when provided as prophylactic vaccines. Also, the vaccine formulations accelerated gonococcal clearance when provided as a single therapeutic dose to treat an already established infection, including against a strain associated with the FC428 clone. Therefore, this study demonstrated that MtrE and Loop 2 are effective gonococcal vaccine antigens when combined with the Th1-polarizing CpG1826 adjuvant.
研究领域:
微生物学
·
免疫学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2022
·
IF 10.761
Linghong Huang,Sufen Peng,Zonghua Liu,Juncheng Zhang,Ning Liu,Jiansheng Lin
Tumor vaccines can inhibit or eliminate tumors by vaccinating hosts with tumor antigens to activate antigen-specific immune responses and have gained wild attention. However, their clinical application efficacy is often comprised due to the low safety and poor efficiency of vaccine adjuvants/carriers. Specifically, the adjuvants/carriers usually could not efficiently recruit antigen presenting cells (APCs) to capture the vaccines or directly damage these cells. Therefore, ideal tumor vaccine adjuvants/carriers should effectively recruit APCs and be friendly to the cells for well keeping their bio-functions. In this work, injectable natural blood plasma hydrogel was used for the first time to encapsulate tumor antigens and adjuvant (Mn 2+ ) for the construction of a personalized tumor vaccine. This kind of natural hydrogel with extremely high bio-safety has great potential to friendly recruit APCs in a biomimetic manner by simulating the natural degradation process of subcutaneous blood stasis. The obtained results show that the natural blood plasma hydrogel-based tumor vaccines could significantly promote the recruitment of APCs, well maintain the immuno-functions of the cells, and finally induce efficient anti-tumor immune responses. Compared with traditional tumor vaccines, this natural blood plasma-based hydrogel provides a new strategy for the development of safe and effective tumor vaccines.
研究领域:
生物医学工程
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Chu-Xin Li,Yongdan Qi,Yingge Chen,Yu Zhang,Bin Li,Jun Feng,Xian-Zheng Zhang
Morphology tuning is a potent strategy to modulate physiological effects of synthetic biomaterials, but it is rarely explored in microbe-based biochemicals due to the lack of artificial adjustability. Inspired by the interesting phenomenon of microbial transformation, Escherichia coli is rationally adjusted into filamentous morphology-adjusted bacteria (MABac) via chemical stimulation to prepare a bacteria-based vaccine adjuvant/carrier. Inactivated MABac display stronger immunogenicity and special delivery patterns (phagosome escape and cytoplasmic retention) that are sharply distinct from the short rod-shaped bacteria parent (Bac). Transcriptomic study further offers solid evidence for deeply understanding the in vivo activity of MABac-based vaccine, which more effectively motivates multiple cytosolic immune pathways (such as NOD-like receptors and STING) and induces pleiotropic immune responses in comparison with Bac. Harnessing the special functions caused by morphology tuning, the MABac-based adjuvant/carrier significantly improves the immunogenicity and delivery profile of cancer antigens in vivo, thus boosting cancer-specific immunity against the melanoma challenge. This study validates the feasibility of tuning bacterial morphology to improve their biological effects, establishing a facile engineering strategy that upgrades bacterial properties and functions without complex procedures like gene editing.
研究领域:
生物技术
·
免疫学
·
癌症研究
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Matter
·
2023
·
IF 18.9
Zhiqin Cao,Lanfang Ren,Le Niu,Rui Zhao,Nanhui Liu,Qi Zhuang,Feng Pan,Zhuang Liu,Yiyun Cheng,Yang Yang,Qian Chen
Summary Cancer vaccines have attracted tremendous interest in the field of cancer immunotherapy due to their ability to trigger tumor-specific immune responses to destroy cancer cells. Herein, we demonstrate that dendrimers coordinated with manganese ions (GT-Mn 2+ ) could self-assemble with peptides to form a cancer vaccine, which could be internalized by dendritic cells (DCs) via specific macropinocytosis-dependent and lipid-raft-related pathways and then dissociated gradually to release peptides to achieve efficient antigen cross-presentation and stimulate the cGAS-STING pathway. Additionally, GT-Mn 2+ could package multiple neoantigens to form an effective “personalized” cancer vaccine and has exhibited excellent therapeutic effects when used in combination with anti-PD-L1. Thus, our work presents an innovative peptide carrier to construct an effective “personalized” cancer vaccine that shows great promise to achieve effective cancer immunotherapy for different patients in clinic.
研究领域:
癌症免疫疗法
·
纳米医学
·
疫苗学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Lijie Qiao,Na Fan,Yupei Zhang,Yuting Chen,Shugang Qin,Xiangrong Song
Messenger RNA (mRNA) vaccine efficacy requires delivery systems that maximize antigen expression while precisely modulating innate immune activation. However, many conventional adjuvants induce type I interferons that inadvertently suppress mRNA translation, compromising vaccine efficacy. To overcome this limitation, we engineered a multifunctional lipid nanoparticle (LNP) by partially substituting a fraction of the structural lipid cholesterol with SitoC7A - a conjugate of sitosterol and the STING (Stimulator of Interferon Genes) agonist (C7A) linked via a reducible disulfide bond. This single SitoC7A component serves dual roles: its disulfide bond markedly enhances LNP uptake by dendritic cells (DCs) and boosts mRNA translation, while its C7A moiety selectively triggers STING signaling within DCs, avoiding systemic interferon responses. This integrated design yielded robust DC maturation and superior antigen presentation. In murine models, SitoC7A-LNPs encapsulating SARS-CoV-2 mRNA elicited potent protective immunity, while tumor antigen-loaded LNPs significantly suppressed lymphoma progression. We introduce a principle for the novel LNP design wherein a single engineered lipid simultaneously provides structural support, enhances mRNA delivery and expression specifically in key immune cells, and delivers spatially controlled adjuvanticity creating a versatile and potent platform for next-generation mRNA vaccines.
研究领域:
免疫学
·
肿瘤学
·
纳米医学
·
疫苗学
·
分子药剂学
·
转化医学
·
先天免疫
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Qiu-Ling Zhang,Sheng Hong,Xue Dong,Di-Wei Zheng,Jun-Long Liang,Xue-Feng Bai,Xia-Nan Wang,Zi-Yi Han,Xian-Zheng Zhang
Cancer vaccines-based cancer immunotherapy has drawn widespread concern. However, insufficient cancer antigens and inefficient antigen presentation lead to low immune response rate, which greatly restrict the practical application of cancer vaccines. Here, inspired by intracellular proteasome-mediated protein degradation pathway, we report an antigen presentation simplification strategy by extracellular degradation of antigen proteins into peptides with proteolytic enzyme for improving the utilization of cancer antigens and arousing restricted cancer immunity . The pre-degraded antigen peptides are first validated to exhibit an increased capacity on antigen-presenting cell (APC) stimulation compared with proteins and still reserve antigen specificity and major histocompatibility complex (MHC) affinity. Furthermore, by coordinating the pre-degraded peptides with calcium phosphate nanoparticles (CaP), a CaP-peptide vaccine (CaP-Pep) is constructed, which is verified to induce an efficient personalized immune response in vivo for multi-model anti-cancer therapy. Notably, this bioinspired strategy based on extracellular enzymatic hydrolysis for vaccine construction is not only applicable for multiple types of cancers, but also shows great potential in expanding immunology fields and translational medicine.
研究领域:
癌症免疫学
·
纳米医学
·
疫苗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-21
·
IF 12.6
Yang Yi,Guo Jiaxin,Qi Jialong,Deng Wenxia,Hu Jialin,Hasan Muhammad Waqqas,Deng Fei,Zhou You,Song Zhengji,Deng Wei,Chen Wenjie
Immune checkpoint blockade therapy (iCBT) has revolutionized cancer treatment, however, there is a low response rate, especially in treating postsurgical reoccurring tumors. Vaccine based immunotherapy can sensitize iCBT, but its development was largely hindered by inefficient delivery and high requirements of storage. In this study, the vaccine loaded with immunostimulant was employed to improve iCBT-based adjuvant postsurgical therapy. A lyophilized, antigen E7 peptide and manganese ion (Mn 2+ ) co-delivered tumor vaccine was developed based on lipid nanoparticles (EM@LNP). The vaccination efficacy was examined in both prophylactic and therapeutic schemes in murine subcutaneous models, the synergetic effect of vaccination combined with anti-PD-1 therapy was further investigated in post-operative tumor model. EM@LNP vaccination elicited effective CD8 + T cell response through modulating tumor immunosuppressive microenvironment and conferring immune memory, demonstrating potent immunization in both preventive and therapeutic schemes. What’s more, EM@LNP vaccination orchestrated with iCBT, efficiently repressing tumor recurrence. Further mechanism studies using inhibitor for cells invitro and the investigation using STING −/− mice confirmed that the cGAS-STING signaling pathway activated by Mn 2+ is indispensable for LNP vaccination and the coordination with iCBT-based adjuvant immunotherapy. In summary, this study shows a lyophilized LNP vaccine could significantly amplify iCBT efficiency, providing a translational strategy of adjuvant immunotherapy for treating postsurgical tumor recurrence. Graphical abstract
研究领域:
肿瘤学
·
免疫学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）