bims-traimu 2023-12-03 papers

Issue of 2023–12–03
five papers selected by
Yantong Wan, Southern Medical University

Adv Sci (Weinh). 2023 Nov 27. e2305081

Engineered Probiotic-Based Personalized Cancer Vaccine Potentiates Antitumor Immunity through Initiating Trained Immunity.

Zhaoxia Chen, Tuying Yong, Zhaohan Wei, Xiaoqiong Zhang, Xin Li, Jiaqi Qin, Jianye Li, Jun Hu, Xiangliang Yang, Lu Gan.

Cancer vaccines hold great potential for clinical cancer treatment by eliciting T cell-mediated immunity. However, the limited numbers of antigen-presenting cells (APCs) at the injection sites, the insufficient tumor antigen phagocytosis by APCs, and the presence of a strong tumor immunosuppressive microenvironment severely compromise the efficacy of cancer vaccines. Trained innate immunity may promote tumor antigen-specific adaptive immunity. Here, a personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and β-glucan, a trained immunity inducer. After subcutaneous injection, the cancer vaccine delivering model antigen OVA (BG/OVA@EcN) is highly accumulated and phagocytosed by macrophages at the injection sites to induce trained immunity. The trained macrophages may recruit dendritic cells (DCs) to facilitate BG/OVA@EcN phagocytosis and the subsequent DC maturation and T cell activation. In addition, BG/OVA@EcN remarkably enhances the circulating trained monocytes/macrophages, promoting differentiation into M1-like macrophages in tumor tissues. BG/OVA@EcN generates strong prophylactic and therapeutic efficacy to inhibit tumor growth by inducing potent adaptive antitumor immunity and long-term immune memory. Importantly, the cancer vaccine delivering autologous tumor antigens efficiently prevents postoperative tumor recurrence. This platform offers a facile translatable strategy to efficiently integrate trained immunity and adaptive immunity for personalized cancer immunotherapy.

Keywords: antitumor immunity; cancer vaccines; probiotics; trained immunity; β-glucan

DOI: https://doi.org/10.1002/advs.202305081

Ann Parasitol. 2023 11 27. 69 0

The double-sided effects of Mycobacterium Bovis bacillus Calmette-Guérin vaccine on helminthic infections.

Tahereh Mikaeili Galeh, Behzad Bijani, Seyedeh Zahra Hashemi, Elham Kia Lashaki, Samira Dodangeh.

Bacillus Calmette-Guérin (BCG), a live attenuated strain derived from an isolate of Mycobacterium bovis, is one of the childhood vaccinations widely used against tuberculosis (TB). In addition to its effects on mycobacterial diseases, the information has shown the protection effect of BCG in helminthic diseases. In the current review, the role of BCG vaccine in non-specific protection helminthic infection is reviewed. In human alveolar echinococcosis (AE), treatment with BCG enhances host's innate immune response against the parasite via the number and activation of monocytes. In cysticercosis, despite the enhancement of Th1-biased immune responses by coadministration of rcC1 plus BCG-DNA, the level of induced protection did not increase compared to immunization with rcC1 antigen alone. Also, pretreatment of mice with live BCG vaccine induced a high level of protection against subsequent parasite infection with Taenia taeniaeformis. The reduction of the parasite burden in mice infected with Mesocestoides corti that received two doses of BCG post-infection demonstrated the therapeutic effect of BCG. The protective potential of the schistosomula/BCG vaccine against Schistosoma japonicum in sheep study showed a reduction in the number of adult worms and mean faecal egg counts post-challenge. In trichinellosis, BCG can induce hyperplasia of the reticuloendothelial system and activation of macrophages in mice. Therefore, these data revealed that BCG vaccination can exert non-specific protective effects for the prevention of diseases other than tuberculosis. Medicinal doses of BCG may be considered a new approach to the treatment of helminth infections.

DOI: https://doi.org/10.17420/ap6902.510

Small. 2023 Nov 27. e2307066

Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer-Membrane-Vesicle Vaccine.

Saugata Majumder, Shreya Das, Peng Li, Nicole Yang, Hazel Dellario, Haixin Sui, Ziqiang Guan, Wei Sun.

A new Yersinia pseudotuberculosis mutant strain, YptbS46, carrying the lpxE insertion and pmrF-J deletion is constructed and shown to exclusively produce monophosphoryl lipid A (MPLA) having adjuvant properties. Outer membrane vesicles (OMVs) isolated from YptbS46 harboring an lcrV expression plasmid, pSMV13, are designated OMV46 -LcrV, which contained MPLA and high amounts of LcrV (Low Calcium response V) and displayed low activation of Toll-like receptor 4 (TLR4). Intramuscular prime-boost immunization with 30 µg of of OMV46 -LcrV exhibited substantially reduced reactogenicity than the parent OMV44 -LcrV and conferred complete protection to mice against a high-dose of respiratory Y. pestis challenge. OMV46 -LcrV immunization induced robust adaptive responses in both lung mucosal and systemic compartments and orchestrated innate immunity in the lung, which are correlated with rapid bacterial clearance and unremarkable lung damage during Y. pestis challenge. Additionally, OMV46 -LcrV immunization conferred long-term protection. Moreover, immunization with reduced doses of OMV46 -LcrV exhibited further lower reactogenicity and still provided great protection against pneumonic plague. The studies strongly demonstrate the feasibility of OMV46 -LcrV as a new type of plague vaccine candidate.

Keywords: OUTER membrane vesicles; Y. pestis; monophosphoryl lipid A; plague vaccine; protective immunity

DOI: https://doi.org/10.1002/smll.202307066

Nat Metab. 2023 Nov 27.

Efferocytosis-induced lactate enables the proliferation of pro-resolving macrophages to mediate tissue repair.

David Ngai, Maaike Schilperoort, Ira Tabas.

The clearance of apoptotic cells by macrophages (efferocytosis) prevents necrosis and inflammation and activates pro-resolving pathways, including continual efferocytosis. A key resolution process in vivo is efferocytosis-induced macrophage proliferation (EIMP), in which apoptotic cell-derived nucleotides trigger Myc-mediated proliferation of pro-resolving macrophages. Here we show that EIMP requires a second input that is integrated with cellular metabolism, notably efferocytosis-induced lactate production. Lactate signalling via GPR132 promotes Myc protein stabilization and subsequent macrophage proliferation. This mechanism is validated in vivo using a mouse model of dexamethasone-induced thymocyte apoptosis, which elevates apoptotic cell burden and requires efferocytosis to prevent inflammation and necrosis. Thus, EIMP, a key process in tissue resolution, requires inputs from two independent processes: a signalling pathway induced by apoptotic cell-derived nucleotides and a cellular metabolism pathway involving lactate production. These findings illustrate how seemingly distinct pathways in efferocytosing macrophages are integrated to carry out a key process in tissue resolution.

DOI: https://doi.org/10.1038/s42255-023-00921-9

Int Immunopharmacol. 2023 Nov 24. pii: S1567-5769(23)01598-9. [Epub ahead of print]126 111271

PVB exerts anti-inflammatory effects by inhibiting the activation of MAPK and NF-κB signaling pathways and ROS generation in neutrophils.

Jiafu Ouyang, Yinghao Hong, Yantong Wan, Xiangyi He, Bingxuan Geng, Xinxing Yang, Jing Xiang, Junwei Cai, Zhenhua Zeng, Zhifeng Liu, Na Peng, Yong Jiang, Jinghua Liu.

Pinaverium bromide (PVB) has been shown to protect mice against sepsis, which is predominantly attributed to PVB-mediated anti-inflammatory effects by inhibiting primed neutrophils to produce proinflammatory cytokines. However, the underlying mechanism(s) by which PVB affects neutrophils remains unknown. In this study, we report that treatment with PVB either before or after LPS stimulation attenuated IL-1β and TNF-α expression at both mRNA and protein levels in LPS-activated murine neutrophils. Further experiments revealed that PVB inhibited the phosphorylation of ERK, JNK, and IκBα in LPS-stimulated murine neutrophils. Moreover, PVB reduced reactive oxygen species (ROS) levels via regulating NADPH oxidase 2 (NOX2) activity, as represented by inhibiting p47phox translocation from the cytoplasm to the cellular membrane. Importantly, PVB significantly attenuated IL-1β, TNF-α, IL-6, CXCL1 production in both LPS-stimulated low density neutrophils (LDNs) and normal density neutrophils (NDNs) isolated from septic patients. Collectively, we demonstrated that PVB exerts anti-inflammatory effect by attenuating ROS generation and suppressing the activation of MAPK and NF-κB signaling pathways, suggesting that PVB may act as a potential therapeutic agent for sepsis by inhibiting neutrophil priming and activation.

Keywords: Cytokine; NADPH oxidase 2; Neutrophil; Pinaverium bromide; ROS; Sepsis

DOI: https://doi.org/10.1016/j.intimp.2023.111271