Protective Immunity Research Articles

A novel method for recombinant mammalian-expressed S-HBsAg virus-like particle production for assembly status analysis and improved anti-HBs serology.

The Hepatitis B surface antigen (HBsAg) as the only lipid-associated envelope protein of the Hepatitis B virus (HBV) acts as cellular attachment and entry mediator of HBV making it the main target of neutralizing antibodies to provide HBV immunity after infection or vaccination. Despite its central role in inducing protective immunity, there is however a surprising lack of comparative studies examining different HBsAgs and their ability to detect anti-HBs antibodies. On the contrary, various time-consuming complex HBsAg production protocols have been established, which result in structurally and functionally insufficiently characterized HBsAg. Here, we present an easy-to-perform, streamlined and robust method for recombinant S-HBsAg virus-like particle (VLP) production by transient expression in mammalian cells and purification from the cell lysate with the aim of displaying uniform antigenic epitopes on the surface to improve serological detection of anti-HBs antibodies. We not only compare assembly status and particle composition by transmission electron microscopy and mass photometry of our S-HBsAg and of commonly used HBsAg reference samples, but also assess their antigenic quality and functional suitability for anti-HBs antibody detection to identify the best performing sample for serological screenings. While we found that serum-isolated and recombinant HBsAg VLPs are assembled differently, our S-HBsAg VLPs detected anti-HBs antibodies with the highest sensitivity and specificity in multiplex serology when compared to yeast or serum HBsAg making it the most suitable antigen for analysis of HBV immunity through anti-HBs serostatus.

Unraveling the impact of SARS-CoV-2 mutations on immunity: insights from innate immune recognition to antibody and T cell responses

Throughout the COVID-19 pandemic, the emergence of new viral variants has challenged public health efforts, often evading antibody responses generated by infections and vaccinations. This immune escape has led to waves of breakthrough infections, raising questions about the efficacy and durability of immune protection. Here we focus on the impact of SARS-CoV-2 Delta and Omicron spike mutations on ACE-2 receptor binding, protein stability, and immune response evasion. Delta and Omicron variants had 3–5 times higher binding affinities to ACE-2 than the ancestral strain (KDwt = 23.4 nM, KDDelta = 8.08 nM, KDBA.1 = 4.77 nM, KDBA.2 = 4.47 nM). The pattern recognition molecule mannose-binding lectin (MBL) has been shown to recognize the spike protein. Here we found that MBL binding remained largely unchanged across the variants, even after introducing mutations at single glycan sites. Although MBL binding decreased post-vaccination, it increased by 2.6-fold upon IgG depletion, suggesting a compensatory or redundant role in immune recognition. Notably, we identified two glycan sites (N717 and N801) as potentially essential for the structural integrity of the spike protein. We also evaluated the antibody and T cell responses. Neutralization by serum immunoglobulins was predominantly mediated by IgG rather than IgA and was markedly impaired against the Delta (5.8-fold decrease) and Omicron variants BA.1 (17.4-fold) and BA.2 (14.2-fold). T cell responses, initially conserved, waned rapidly within 3 months post-Omicron infection. Our data suggests that immune imprinting may have hindered antibody and T cell responses toward the variants. Overall, despite decreased antibody neutralization, MBL recognition and T cell responses were generally unaffected by the variants. These findings extend our understanding of the complex interplay between viral adaptation and immune response, underscoring the importance of considering MBL interactions, immune imprinting, and viral evolution dynamics in developing new vaccine and treatment strategies.

Tuft cells promote human intestinal epithelium regeneration as reserve stem cells after irradiation

Intestinal epithelium regeneration is crucial for homeostatic maintenance of the intestinal functions. A recent study published in Nature uncovers tuft cells as an unexpected key player in the regenerative process. Human tuft cells, traditionally recognized for their involvement in immune defense and pathogen protection, were found to exhibit stem cell-like properties following radiation-induced injury. These cells not only resist damage but also have the ability to generate functional stem cells, promoting the repair of the intestinal epithelium. This finding suggests that tuft cells may function as a reserve pool of stem cells, essential for efficient intestinal regeneration after injury.

Skin as outermost immune organ of vertebrates that elicits robust early immune responses after immunization with glycoprotein of spring viraemia of carp virus.

As the outermost immune organ in vertebrates, the skin serves as the primary interface with the external environment and plays a crucial role in initiating the early immune response. The skin contains a variety of immune cells that induce mucosal and systemic immune responses, rendering it a prime target for vaccination strategies. Insight into the mechanisms through which vaccination triggers early immune responses is paramount for advancing animal and human health, yet our current understanding remains limited. Given its significance in vertebrate evolution, teleost fish emerges as an excellent model for investigating the early immune response of skin. In this study, we demonstrate that significant quantities of vaccine can be absorbed by the skin and transported to the body through dermis and muscle metabolism by immerses immune zebrafish with glycoprotein of spring viraemia of carp virus. Immersion immunization can elicit robust and enduring immune protection, with the skin triggering a potent immune response early in the immunization process. Analysis of the skin transcriptome revealed the involvement of numerous immune-related genes in the immersion immune response, with indications that HSP70 and MAPK signals might play pivotal roles in the immune process induced by glycoprotein. Co-immunoprecipitation and cell co-localization studies confirmed the interaction between glycoprotein and HSP70. Subsequent research demonstrated that overexpression or inhibition of HSP70 could respectively enhance or impede the expression of JNK and related proteins. However, the survival rate and immune response of HSP70 inhibited zebrafish with glycoprotein treatment were significantly reduced. These findings propose that the interaction between glycoprotein and HSP70 may activate JNK, thereby modulating mucosal and systemic immune responses induced by glycoprotein. This investigation offers novel insights and a foundational understanding of early skin immune reactions.

TNF-α exacerbates SARS-CoV-2 infection by stimulating CXCL1 production from macrophages.

Since most genetically modified mice are C57BL/6 background, a mouse-adapted SARS-CoV-2 that causes lethal infection in young C57BL/6 mice is useful for studying innate immune protection against SARS-CoV-2 infection. Here, we established two mouse-adapted SARS-CoV-2, ancestral and Delta variants, by serial passaging 80 times in C57BL/6 mice. Although young C57BL/6 mice were resistant to infection with the mouse-adapted ancestral SARS-CoV-2, the mouse-adapted SARS-CoV-2 Delta variant caused lethal infection in young C57BL/6 mice. In contrast, MyD88 and IFNAR1 KO mice exhibited resistance to lethal infection with the mouse-adapted SARS-CoV-2 Delta variant. Treatment with recombinant IFN-α/β at the time of infection protected mice from lethal infection with the mouse-adapted SARS-CoV-2 Delta variant, but intranasal administration of recombinant IFN-α/β at 2 days post infection exacerbated the disease severity following the mouse-adapted ancestral SARS-CoV-2 infection. Moreover, we showed that TNF-α amplified by type I IFN signals exacerbated the SARS-CoV-2 infection by stimulating CXCL1 production from macrophages and neutrophil recruitment into the lung tissue. Finally, we showed that intravenous administration to mice or hamsters with TNF protease inhibitor 2 alleviated the severity of SARS-CoV-2 and influenza virus infection. Our results uncover an unexpected mechanism by which type I interferon-mediated TNF-α signaling exacerbates the disease severity and will aid in the development of novel therapeutic strategies to treat respiratory virus infection and associated diseases such as influenza and COVID-19.

MAIT cell plasticity enables functional adaptation that drives antibacterial immune protection.

Mucosal-associated invariant T (MAIT) cells are known for their rapid effector functions and antibacterial immune protection. Here, we define the plasticity of interferon-γ (IFN-γ)-producing MAIT1 and interleukin-17A (IL-17A)-producing MAIT17 cell subsets in vivo. Whereas T-bet+ MAIT1 cells remained stable in all experimental settings, after adoptive transfer or acute Legionella or Francisella infection, RORγt+ MAIT17 cells could undergo phenotypic and functional conversion into both RORγt+T-bet+ MAIT1/17 and RORγt-T-bet+ MAIT1 cells. This plasticity ensured that MAIT17 cells played a dominant role in generating antibacterial MAIT1 responses in mucosal tissues. Single-cell transcriptomics revealed that MAIT17-derived MAIT1 cells were distinct from canonical MAIT1 cells yet could migrate out of mucosal tissues to contribute to the global MAIT1 pool in subsequent systemic infections. Human IL-17A-secreting MAIT cells also showed similar functional plasticity. Our findings have broad implications for understanding the role of MAIT cells in combatting infections and their potential utility in MAIT cell-targeted vaccines.

Enhancing protective immunity against SARS-CoV-2 with a self-amplifying RNA lipid nanoparticle vaccine.

RNA-based vaccines against SARS-CoV-2 have demonstrated promising protective immunity against the global COVID-19 epidemic. Enhancing the intensity and duration of mRNA antigen expression is anticipated to markedly boost antiviral immune responses. Self-amplifying RNA (saRNA) represents a next-generation platform for RNA-based vaccines, amplifying transcripts in situ to augment the expression of encoded immunogens. Here, we develop a saRNA nanovaccine, formulated with a mutated saRNA encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, encapsulated within a lipid nanoparticle (LNP-saRNA-RBD). This LNP-saRNA vaccine platform enables efficient delivery of saRNA-RBD, inducing enhanced and prolonged expression of the RBD antigen. LNP-saRNA-RBD vaccination stimulated the generation of antigen-specific T cells, promoting their differentiation into a long-lived effector memory phenotype. Immunization with LNP-saRNA-RBD induced a germinal center response in draining lymph nodes, leading to the production of anti-RBD IgG antibodies with the ability to neutralize SARS-CoV-2 pseudovirus. Furthermore, prime-boost immunizations with LNP-saRNA-RBD conferred protection to mice against SARS-CoV-2 challenge by suppressing viral infection and replication, as well as pulmonary inflammatory responses and associated damage. Taken together, these findings provide strong support for advancing the development of LNP-saRNA-RBD as a safe and efficacious vaccine candidate against SARS-CoV-2 infection.

A penta-component mpox mRNA vaccine induces protective immunity in nonhuman primates

The recent worldwide outbreaks of mpox prioritize the development of a safe and effective mRNA vaccine. The contemporary mpox virus (MPXV) exhibits changing virological and epidemiological features, notably affecting populations already vulnerable to human immunodeficiency virus (HIV). Herein, we profile the immunogenicity of AR-MPXV5, a penta-component mRNA vaccine targeting five specific proteins (M1R, E8L, A29L, A35R, and B6R) from the representative contemporary MPXV clade II strain, in both naive and simian immunodeficiency virus (SIV)-infected nonhuman primates. Immunization with two doses of AR-MPXV5 to cynomolgus macaques effectively elicits antibody responses and cellular responses. Importantly, based on the challenge model with a contemporary MPXV clade II strain, AR-MPXV5 demonstrates effective efficacy in preventing skin lesions, eliminating viremia and reducing viral loads in multiple tissues after challenge in naive male animals. More importantly, AR-MPXV5 is well-tolerated in stable chronic SIV-infected rhesus monkeys, while eliciting comparable MPXV-specific humoral and cellular responses in both naive and SIV-infected monkeys. Together, these results support further clinical development of the AR-MPXV5 vaccine.

Enhancing the Deformability of the Adjuvant: Achieving Lymph Node Targeted Delivery to Elicit a Long-Lasting Immune Protection.

A key challenge in vaccine development is to inducean effective and durable immune response. Live virus vaccines induce lifelong antibody responses; however, the immune responses induced by inactivated or subunit vaccines decrease gradually. Activation of the germinal center (GC) reaction, which generates long-lived plasma cells (LLPCs), is a key mediator of long-term antibody responses. To enhance the activation of GC, lymph node-targeted delivery of the vaccine is promoted by enhancing the deformability of the delivery vector. In this study, a double emulsion is designed with strong deformability and containing chitosan nanoparticles (CSNP) in the internal aqueous phase (WNP) for efficient antigen loading, called WNP/O/W. The flexible oil layer and the internally loaded positively charged particles endow the emulsion with strong deformability, continuously enrich model antigen ovalbumin(OVA)in the lymph nodes, activate germinal center B (GC B) cells and T follicular helper (TFH) cells, induce LLPCs, and obtain high-level antibody persistence for more than 5 months, which is significantly better than the traditional oil emulsion adjuvant. Concurrently, it also improves the immune-protective effect in aged mice. Altogether, these results indicate that WNP/O/W achieves lymph node targeted delivery by strengthening deformability, generating high-intensity antibody responses, and long-lasting immune protection.

Cross-reactivity in Adaptive Immunity: An Overview

Cross-reactivity in adaptive immunity refers to the ability of immune cells to recognize and respond to similar but distinct antigens. This phenomenon, while aiding in the recognition and defense against diverse pathogens, can also lead to unintended immune responses, including autoimmune reactions. The review explores key mechanisms underlying cross-reactivity, including molecular mimicry, T cell receptor degeneracy, and antibody cross-recognition. It discusses the dual role of cross-reactivity in infectious diseases, where it contributes to both protective immunity and potential disease enhancement, as seen in infections like dengue and Zika. Cross-reactivity is also implicated in autoimmunity, where immune responses to microbial antigens can mistakenly target self-tissues, potentially triggering conditions such as type 1 diabetes and multiple sclerosis. Additionally, the review addresses the implications of cross-reactivity in vaccine design, emphasizing the need to balance broad immune protection with safety, as well as challenges in immunotherapy where cross-reactivity may lead to off-target effects. Understanding cross-reactivity is essential to leveraging adaptive immunity effectively while minimizing potential adverse effects, with applications spanning infection control, vaccine development, and therapeutic interventions in immune-mediated diseases. Keywords: Adaptive immunity, Cross-reactivity, Molecular mimicry, Autoimmunity, Vaccine development, Immunotherapy

Role of route of delivery on Chlamydia abortus vaccine-induced immune responses and genital tract immunity in mice.

We investigated if the efficacy of a Chlamydia abortus (Cab) subunit vaccine is influenced by route of administration. Thus, female CBA/J mice were immunized either by mucosal or systemic routes with Vibrio cholerae ghost (VCG)-based vaccine expressing T and B cell epitopes of Cab polymorphic membrane protein (Pmp) 18D, termed rVCG-Pmp18.3. Vaccine evaluation revealed that all routes of vaccine delivery induced a Th1-type antibody response after a prime boost or three-dose immunization regimen. Also, the intranasal and rectal mucosal and intramuscular systemic routes induced cross-reactive neutralizing antibodies against homologous and heterologous Cab strains. Irrespective of the route of immunization, the vaccine elicited a Th1-type cytokine response (IFN-γ/IL-4 >1) in immunized mice. Analysis of reduction in genital Cab burden as an index of protection showed that immunization induced substantial degrees of protection against infection, irrespective of route of delivery with the intranasal and rectal mucosal routes showing superior levels of protection 12 days postchallenge. Furthermore, there was correlation between the humoral and cellular immune response and protection was associated with the Cab-specific serum IgG antibody avidity and IFN-γ. Thus, while route of administration impacts vaccine efficacy, the rVCG-Pmp18.3-induced protective immunity against Cab respiratory infection can be accomplished by both mucosal and systemic immunization.

Natural Killer Cell Phenotypes and Clinical Outcomes in Pediatric Kidney Transplantation.

Natural killer (NK) cells have gained recognition for playing an integral role in both alloimmunity and protective immunity, particularly viral infection control, in solid organ transplantation. Using data from the Clinical Trials in Organ Transplantation in Children (CTOTC) study entitled, "Immune Development in Pediatric Transplantation," (NCT00951353), we aimed to identify NK cell phenotypes that were associated with viral infection versus alloreactive events during the first year after transplantation. We also examined the relationship between NK cells with 7-year patient and allograft survival using the Scientific Registry for Transplant Recipients (SRTR) database. A secondary analysis of peripheral blood mononuclear cells from 98 children aged 1-20 years old with kidney transplants was conducted using multiparameter flow cytometry for the following NK cell phenotypes: CD56bright, CD56dim, and CD56negative. We associated these phenotypes with either viral infection or alloimmunity (de novo donor-specific antibody (dnDSA) development or acute rejection), using Fine-Gray subdistribution hazard models for competing risks. Secondary outcomes included allograft and patient survival. We demonstrated that specific baseline NK cell phenotypes obtained prior to transplantation may be associated with either viral infection or alloimmunity. An elevation in CD56dim frequency was associated with an increased risk of infection, while an increase in CD56negative absolute count was associated with an increased risk of an alloimmune event. NK cells were not associated with graft survival. NK cell phenotyping may be a useful tool to help differentiate infectious from alloimmune risk.

Atopic dermatitis: pathogenesis and therapeutic intervention.

The skin serves as the first protective barrier fornonspecific immunity and encompassesa vast network of skin-associated immune cells. Atopic dermatitis (AD) is a prevalent inflammatory skin disease that affects individuals of all ages and races, with a complex pathogenesis intricately linked to genetic, environmental factors, skin barrier dysfunction as well as immune dysfunction. Individuals diagnosed with AD frequently exhibit genetic predispositions, characterized by mutations that impactthe structural integrity of the skin barrier. This barrier dysfunction leads to the release of alarmins, activating the type 2 immune pathway and recruiting various immune cells to the skin, where they coordinate cutaneous immune responses. In this review, we summarize experimental models of AD and provide an overview of its pathogenesis and the therapeutic interventions. We focus on elucidating the intricate interplay between the immune system of the skin and the complex regulatory mechanisms, as well as commonly used treatments for AD, aiming to systematically understand the cellular and molecular crosstalk in AD-affected skin. Our overarching objective is to provide novel insights and inform potential clinical interventions to reduce the incidence and impact of AD.

Serotype 3 Streptococcus pneumoniae Escapes the Immune Responses Induced by PCV13 in Mice With High Susceptibility to Infection.

Streptococcus pneumoniae (pneumococcus) is a common cause of respiratory and invasive infections in humans. PCV13, a pneumococcal conjugate vaccine used globally, is highly effective against diseases caused by pneumococcal serotypes included in its formulation. However, one of them, the serotype 3 (ST3) is still being relatively commonly isolated from patients, suggesting an escape from vaccine-induced immunity. The thick capsule produced by ST3 facilitates bacterial evasion from the immune system. Additionally, host immune responses may influence the outcome of ST3 infection. Here we evaluated the influence of inflammation in the adaptive immune responses and protection induced by PCV13 against ST3, using two outbred mice lines that were phenotypically selected for high (AIRmax) and low (AIRmin) inflammatory responses. AIRmin and AIRmax mice were immunized with PCV13. Inbred BALB/c mice were used as reference for vaccine efficacy. Induction of IgG against polysaccharides (PS) from pneumococcal serotype 1 (ST1) and ST3 were evaluated by ELISA. Protection was tested against invasive infections with ST1 and ST3 pneumococcal strains. Sera were compared by IgG binding to pneumococcal surface, induction of pneumococcal agglutination and opsonophagocytosis. The phagocytic capacity of mice-derived neutrophils was also evaluated. Immunization of AIRmin, AIRmax and BALB/c mice with PCV13 induced IgG against PS from ST1 and ST3 pneumococci. Despite vaccination, AIRmin mice were not protected against fatal infection with ST3. Sera from AIRmin mice immunized with PCV13 presented lower levels of anti-PS3 IgG, with reduced capacity to bind to pneumococcal surface. Reduced capacity to induce opsonophagocytosis of ST3 pneumococci in vitro was also observed. Conversely, PCV13 protected AIRmin mice against fatal infection with ST1 and this correlated with the capacity of the sera to induce ST1 opsonophagocytosis. Our results show that both host and bacterial features can influence the outcome of protection induced by PCV13 against ST3 pneumococcal infection.

Adjuvanting a subunit novel variant IBDV vaccine to induce protective immunity

Adjuvanting a subunit novel variant IBDV vaccine to induce protective immunity

A Computational Approach for Designing and Validating Small Interfering RNA against SARS-CoV-2 Variants.

The aim of this study is to develop a novel antiviral strategy capable of efficiently targeting a broad set of SARS-CoV-2 variants. Since the first emergence of SARS-CoV-2, it has rapidly transformed into a global pandemic, posing an unprecedented threat to public health. SARS-CoV-2 is prone to mutation and continues to evolve, leading to the emergence of new variants capable of escaping immune protection achieved due to previous SARS-CoV-2 infections or by vaccination. RNA interference (RNAi) is a remarkable biological mechanism that can induce gene silencing by targeting complementary mRNA and inhibiting its translation. In this study, using the computational approach, we predicted the most efficient siRNA capable of inhibiting SARS-CoV-2 variants of concern (VoCs). The presented siRNA was characterized and evaluated for its thermodynamic properties, offsite-target hits, and in silico validation by molecular docking and molecular dynamics simulations (MD) with Human AGO2 protein. The study contributes to the possibility of designing and developing an effective response strategy against existing variants of concerns and preventing further.

A substitution at the cytoplasmic tail of the spike protein enhances SARS-CoV-2 infectivity and immunogenicity

Global dissemination of SARS-CoV-2 Omicron sublineages has provided a sufficient opportunity for natural selection, thus enabling beneficial mutations to emerge. Characterisation of these mutations uncovers the underlying machinery responsible for the fast transmission of Omicron variants and guides vaccine development for combating the COVID-19 pandemic. Through systematic bioinformatics analysis of 496,606 sequences of Omicron variants, we obtained 40amino acid substitutions that occurred with high frequency in the S protein. Utilising pseudoviruses and a trans-complementation system of SARS-CoV-2, we identified the effect of high-frequency mutations on viral infectivity and elucidated the molecular mechanisms. Finally, we evaluated the impact of a key emerging mutation on the immune protection induced by the SARS-CoV-2 VLP mRNA vaccine in a murine model. We identified a proline-to-leucine substitution at the 1263rd residue of the Spike protein, and upon investigating the relative frequencies across multiple Omicron sublineages, we found a trend of increasing frequency for P1263L. The substitution significantly enhances the capacity for S-mediated viral entry and improves the immunogenicity of a virus-like particle mRNA vaccine. Mechanistic studies showed that this mutation is located in the FERM binding motif of the cytoplasmic tail and impairs the interaction between the Sprotein and the Ezrin/Radixin/Moesin proteins. Additionally, this mutation facilitates the incorporation of Sproteins into SARS-CoV-2 virions. This study offers mechanistic insight into the constantly increasing transmissibility of SARS-CoV-2 Omicron variants and provides a meaningful optimisation strategy for vaccine development against SARS-CoV-2. This study was supported by grants from the National Key Research and Development Plan of China (2021YFC2302405, 2022YFC2303200, 2021YFC2300200 and 2022YFC2303400), the National Natural Science Foundation of China (32188101, 32200772, 82422049, 82241082, 32270182, 82372254, 82271872, 82341046, 32100755 and 82102389), Shenzhen Medical Research Fund (B2404002, A2303036), the Shenzhen Bay Laboratory Startup Fund (21330111), Shenzhen San-Ming Project for Prevention and Research on Vector-borne Diseases (SZSM202211023), Yunnan Provincial Science and Technology Project at Southwest United Graduate School (202302AO370010). The New Cornerstone Science Foundation through the New Cornerstone Investigator Program, and the Xplorer Prize from Tencent Foundation.

Self-assembling nanoparticle vaccine elicits a robust protective immune response against avian influenza H5N6 virus in chickens

The continuous circulation and evolution of the H5N6 subtype highly pathogenic avian influenza virus (HPAIV) challenge the development of the global poultry industry and human public health security. To address the potential threat of the H5N6 virus, a secure and efficacious vaccine is urgent. In our research, a self-assembling nanoparticle vaccine presenting the hemagglutinin of the H5N6 AIV was developed based on the ferritin antigen display platform. The results showed that a single-dose vaccination of this nanoparticle vaccine elicited potent hemagglutination inhibition (HI) antibody responses and neutralizing antibody responses in the chickens. Meanwhile, the fused HA-ferritin nanoparticle vaccine induced significantly higher levels of Th1/Th2 immune responses. After a lethal attack with the H5N6 virus, the fused HA-ferritin nanoparticle vaccine conferred chickens with 100 % (10/10) challenge protection. Importantly, the fused HA-ferritin nanoparticle with only 28 hemagglutination units (HAU) provided chickens with immune protection comparable to commercial inactivated vaccines and protected the chickens from severe lung pathological damage. These results in our study support the superiority of ferritin as an antigen display platform and suggest that self-assembled nanoparticle vaccines based on this platform possess the potential as an avian influenza candidate vaccine.

A hypoxia-activated and microenvironment-remodeling nanoplatform for multifunctional imaging and potentiated immunotherapy of cancer

Activatable theranostic systems combining precise diagnosis and robust immune activation have significant potential in cancer treatment. Herein, we develop a versatile nanoplatform integrating hypoxia-activatable molecular imaging with effective photoimmunotherapy for cancer treatment. Our molecular probe features turn-on near-infrared-II (NIR-II) fluorescence and photoacoustic signals in hypoxic tumor environments. It also induces hypoxia-triggered photodynamic and photothermal effects, promoting immunogenic cell death and activating the STING pathway, engaging both innate and adaptive immunity. The molecular probe is formulated with a vascular disrupting agent to amplify the hypoxia-responsive phototheranostic properties, on which M1-like macrophage membrane is camouflaged to shield against premature release while conferring cancer-targeting affinity. The activatable NIR-II fluorescence and photoacoustic imaging enable precise tumor delineation, while the enhanced phototherapy activates tumor-specific cytotoxic T cells, impeding both primary and distant tumor progression and providing protective immunity against rechallenge in 4T1 tumor-bearing female mice. This work advances activatable theranostic protocols for image-guided immunotherapy.

Influence of blood trace elements on immune responses and adverse symptoms subsequent to Sinopharm COVID-19 vaccination

Trace elements, specifically magnesium (Mg), zinc (Zn), and selenium (Se) have been linked with immunomodulatory properties. This research delves into identifying the potential impression of serum levels Mg, Zn, and Se on the protective immunity arisen through Sinopharm COVID-19 vaccine in the vaccinated subjects. Levels of Mg, Zn, and Se, cytokine and antibody production as well as virus neutralization potency were investigated in 75 males and 75 females before and 2 weeks after first and second dose of vaccination. Level of Mg, Zn, and Se did not change significantly before and 2 weeks after first and second dose of vaccine administration. Concentrations of Interleukin (IL)-2, IL-6, and Interferon (IFN)-γ were significantly higher in the supernatant of peripheral blood mononuclear cells (PBMCs) obtained from subjects 2 weeks after both first and second dose of vaccination compared to before vaccination. Serum level IgG was significantly higher 2 weeks after first and second dose of vaccination compared to before vaccination. Serum level IgM was only higher after first dose of vaccination compared with before vaccine. Also, 2 weeks after both first and second dose of vaccination compared to before vaccination, FRNT50 titer was significantly higher. Levels of Mg, Zn, and Se did not significantly correlate with levels of IL-2, IL-6, IFN-γ, IgM and IgG, and FRNT50 after first and second dose of vaccination. No severe unwanted clinical symptoms were detected after vaccination. Mg, Zn, and Se do not play a role in modulating protective immunity during Sinopharm COVID-19 vaccine.