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Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, a key target for regulating the tumor immune microenvironment, is important in cancer treatment and progression. TREM2 is an immune signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor immune responses by inhibiting T cell-mediated immune responses, but it also influences tumorigenesis by affecting NK cell-mediated antitumor immunity. Noticeably, TREM2 expression levels also vary significantly among different tumor cells, and it can regulate tumor progression by modulating various signaling pathways. Above all, by summarizing the role of TREM2 in cancer immunotherapy and the mechanism by which TREM2 regulates tumor progression, this paper clarifies TREM2's role in both tumor progression and cancer therapy, identifying a new therapeutic target for oncology diseases. [ABSTRACT FROM AUTHOR]

The article provides information on pathogen Listeria monocytogenes. According to a research, such pathogen takes advantage of a facet of its host's immune response and it produces a protein called listeriolysin O (LLO) that injects pores into membranes. This action allows the bacterium to escape from intracellular areas charged with its destruction and to replicate and spread.

Many factors restrict honey bees' productivity and pollination potential, especially with the infestation of Greater wax moth, Galleria mellonella L., and synthetic pesticides used to manage this pest. Therefore, a study was conducted to examine the efficacy of oils extracted from Pongamia pinnata, Mentha piperita, Ocimum basilicum, and Thymus vulgaris on the biology and survival of wax moth. The results revealed that all treatments exhibited control over the hatching potential of eggs, and the lowest egg hatchability (6.67%) was observed with peppermint and thyme oil (4%). The larval mortality increased with increasing concentrations of the treatments. The basil oil (4%) showed the highest mortality of 3rd (76.67%) and 7th instar larvae (56.67%). All treatments reduced larval duration, while the time of pupation and adult longevity increased compared to the control. The cellular immune active response of 7th instar larvae at LC50 of these botanicals revealed a decrease in the number of granulocytes and plasmatocytes compared to control. This study demonstrated the potential of botanical pesticides in managing greater wax moth infestations, offering a more environmentally friendly alternative to synthetic pesticides. [ABSTRACT FROM AUTHOR]

The immune response plays a crucial role in preventing diseases, such as infections. There are two types of immune responses, specific and innate immunity, each of which consists of two components: cellular immunity and humoral immunity. Dysfunction in any immune system component increases the risk of developing certain diseases. Systemic lupus erythematosus (SLE), an autoimmune disease in the human body, develops an immune response against its own components. In these patients, due to underlying immune system disorders and receipt of immunosuppressive drugs, the susceptibility to infections is higher than in the general population and is the single largest cause of mortality in this group. COVID-19 infection, which first appeared in late 2019, has caused several concerns in patients with SLE. However, there is no strong proof of additional risk of developing COVID-19 in patients with SLE, and in some cases, studies have shown less severity of the disease in these individuals. This review paper discusses the immune disorders in SLE and COVID-19. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses. [ABSTRACT FROM AUTHOR]

Introduction: Nasopharyngeal colonization is a precondition for mucosal and invasive pneumococcal disease. Prevention of colonization may reduce pneumococcal transmission and disease incidence. Therefore, several protein-based pneumococcal vaccines are currently under investigation. Areas covered: We aimed to better understand the host immune responses to pneumococcal proteins in the upper respiratory tract (URT) that could facilitate the development of serotype-independent pneumococcal vaccines. English peer-reviewed papers reporting immunological mechanisms involved in host immune response to pneumococcal proteins in the URT were retrieved through a PubMed search using the terms 'pneumococcal proteins,' 'nasopharyngeal colonization' and/or 'cellular/humoral host immune response.' Expert opinion: Although pneumococcal protein antigens induce humoral immune responses, as well as IL-17A-mediated immunity, none of them, when used as single antigen, is sufficient to control and broadly protect against pneumococcal colonization. Novel vaccines should contain multiple conserved protein antigens to activate both arms of the immune system and evoke protection against the whole spectrum of pneumococcal variants by reducing, rather than eradicating, pneumococcal carriage. The highest efficacy would likely be achieved when the vaccine is intranasally applied, inducing mucosal immunity and enhancing the first line of defense by restricting pneumococcal density in the URT, which in turn will lead to reduced transmission and protection against disease. [ABSTRACT FROM AUTHOR]

In this paper, a humoral and cellular immunity virus dynamics model with the Beddington-DeAngelis incidence rate is set up. We derive the basic reproductive number R0, the cytotoxic T lymphocytes immune response reproductive number R1, the humoral immune response reproductive number R2, humoral immune response competitive reproductive number R3, and cytotoxic T lymphocytes immune response competitive reproductive number R4, and a full description of the relation between the existence of the equilibria and reproductive numbers is given. The global properties of the five equilibria are obtained by constructing Lyapunov functions. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. Methods: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. Results: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9–97.2), dropping to 77.6% (95%CI 64.7–86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2–90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. Conclusions: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs. [ABSTRACT FROM AUTHOR]

Cellular and humoral immunity exhibit dynamic adaptation to the mutating SARS-CoV-2 virus. It is noteworthy that immune responses differ significantly, influenced by whether a patient has received vaccination or whether there is co-occurrence of naturally acquired and vaccine-induced immunity, known as hybrid immunity. The different immune reactions, conditional on vaccination status and the viral variant involved, bear implications for inflammatory responses, patient outcomes, pathogen transmission rates, and lingering post-COVID conditions. Considering these developments, we have performed a review of recently published literature, aiming to disentangle the intricate relationships among immunological profiles, transmission, the long-term health effects post-COVID infection poses, and the resultant clinical manifestations. This investigation is directed toward understanding the variability in the longevity and potency of cellular and humoral immune responses elicited by immunization and hybrid infection. [ABSTRACT FROM AUTHOR]

With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region’s most prolific subtype (subtype C) would be a significant step forward. In this paper we report on the effect of 2 different adjuvants, AddaVax and AlhydroGel, formulated with HIV-1 subtype C gp140, on the development of binding and neutralising antibody titres in rabbits. AddaVax is a squalene-based oil-in-water nano-emulsion (similar to MF59) which can enhance both cellular and humoral immune responses, whilst AlhydroGel (aluminium hydroxide gel) mainly drives a Th2 response. The gp140 gene tested was derived from the superinfecting virus (SU) from participant CAP256 in the CAPRISA 002 Acute infection cohort. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08. When this soluble Env protein was tested in rabbits, AlhydroGel significantly enhanced soluble Env and V1V2 binding antibodies when compared to AddaVax. Finally, AlhydroGel resulted in significantly higher neutralization titres for a subtype C Tier 1A virus (MW965.26) and increased neutralization breadth to Tier 1A and 1B viruses. However, no autologous Tier 2 neutralisation was observed. These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation. [ABSTRACT FROM AUTHOR]

In this paper, we study the dynamical behavior of a virus model into which cell-mediated and humoral immune responses are incorporated. The global stability of an infection-free equilibrium and four infected equilibria is established via a Lyapunov functional approach. The present construction methods are applicable to a wide range of incidence rates that are monotone increasing with respect to concentration of uninfected cells and concave with respect to the concentration of free virus particles. In addition, when the incidence rate is monotone increasing with respect to concentration of free virus particles, the functional approach plays an important role in determining the global stability of each of the four infected equilibria. This implies that the dynamical behavior of virus prevalence would be determined by basic reproduction numbers when the "saturation effect" for free virus particles appears. We point out that the incidence rate includes not only separable incidence rate but also non-separable incidence rate such as standard incidence and Beddington-DeAngelis functional response. [ABSTRACT FROM AUTHOR]

Coevolution of hosts and their parasites has shaped heterogeneity of effector hemocyte types, providing immune defense reactions with variable effectiveness. In this work, we characterize hemocytes of Drosophila willistoni, a species that has evolved a cellular immune system with extensive variation and a high degree of plasticity. Monoclonal antibodies were raised and used in indirect immunofluorescence experiments to characterize hemocyte subpopulations, follow their functional features and differentiation. Pagocytosis and parasitization assays were used to determine the functional characteristics of hemocyte types. Samples were visualized using confocal and epifluorescence microscopy. We identified a new multinucleated giant hemocyte (MGH) type, which differentiates in the course of the cellular immune response to parasitoids. These cells differentiate in the circulation through nuclear division and cell fusion, and can also be derived from the central hematopoietic organ, the lymph gland. They have a binary function as they take up bacteria by phagocytosis and are involved in the encapsulation and elimination of the parasitoid. Here, we show that, in response to large foreign particles, such as parasitoids, MGHs differentiate, have a binary function and contribute to a highly effective cellular immune response, similar to the foreign body giant cells of vertebrates. [ABSTRACT FROM AUTHOR]

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2–specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity (p < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays (p < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants (p > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses. [ABSTRACT FROM AUTHOR]

The aim of the work is to study the indicators of cellular and humoral immune response and FAN of patients with tonsillitis in children infected with HHV-6 type. Materials and methods of research. In 72 children aged 3--15 years (mean age 8.42 ± 1.44 years), patients with streptococcal tonsillitis of moderate severity, the levels of the main subpopulations of blood lymphocytes were determined using monoclonal antibodies by solid-phase enzyme-linked immunosorbent assay, phagocytic activity of neutrophils (FAN) using the nitrosine tetrazolium reduction test (HCT test) and serum Ig A, Ig M, Ig G levels by radial immunodiffusion. The studies were carried out in the acute period and in the period of convalescence. Mathematical and statistical processing of the data obtained was carried out using Microsoft Excel 2003 and Statistica 6.0 programs. The significance of differences between the mean values was determined using the Student's test (t). Results. Different mechanisms of formation of pathological process at streptococcal tonsillitis at children depending on the concomitant HHV-6 type infection are revealed. In patients with mixed infection in the acute period of tonsillitis determine the signs of deficiency of the cellular immune system with the maximum deviation of CD-lymphocytes (t = 3.13 vs. t = 2.16 in mono-infection), the tension in the humoral link of the immune response Ig deviation (t = 1.63 against t = 0.91 in mono-infection) on the background of phagocytosis violation in terms of FAN deviation (t = 3.22 against t = 2.01 in mono-infection). By the period of convalescence, the restoration of the imbalance of specific and non-specific protection factors does not occur. Increased Ig G content in the acute period is one of the features of streptococcal tonsillitis in children on the background of HHV-6t infection. Conclusions. Concomitant VGL-6 type infection in children with streptococcal tonsillitis affects the mechanisms of formation of the inflammatory process and the reactivity of patients, forming the preconditions for adverse outcomes of the disease. The obtained results can be the basis for early detection of herpes virus infection in patients with tonsillitis, will help to optimize the management of patients in different periods of the disease. [ABSTRACT FROM AUTHOR]

Marchuk's model of a general immune reaction is presented in the paper. The results of investigation of the model are summarized. The qualitative behaviour of solutions to the model and its simplification is described. Many illustrations of recovery process, oscillations or lethal outcomes of a disease are shown. The model with time-dependent immune reactivity is also considered. Periodic dynamics caused by different reasons are compared. In the last section adaptation of the model to tumour-immune interactions is proposed. The role of interleukins in immune processes is taken into account to adapt Marchuk's model to tumour growth dynamics. Possible immunotherapy is also considered in the proposed model. Some preliminary analysis of the model is presented. [ABSTRACT FROM AUTHOR]

Infectious diseases are a predominant problem in human health. While the incidence of many pathogenic infections is controlled by vaccines, some pathogens still pose a challenging task for vaccine researchers. In order to face these challenges, the field of vaccine development has changed tremendously over the last few years. For non-replicating recombinant antigens, novel vaccine delivery systems that attempt to increase the immunogenicity by mimicking structural properties of pathogens are already approved for clinical applications. Lipid-based nanoparticles (LbNPs) of different natures are vesicles made of lipid layers with aqueous cavities, which may carry antigens and other biomolecules either displayed on the surface or encapsulated in the cavity. However, the efficacy profile of recombinant LbNP vaccines is not as high as that of live-attenuated ones. This review gives a compendious picture of two approaches that affect the immunogenicity of recombinant LbNP vaccines: (i) the incorporation of immunostimulatory agents and (ii) the utilization of pre-existing or promiscuous cellular immunity, which might be beneficial for the development of tailored prophylactic and therapeutic LbNP vaccine candidates. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign, chronic, estrogen-dependent condition, present in 10% of women of reproductive age. The condition is associated with chronic pelvic pain and infertility that influence their quality of life, as well as married life and has important socio-economic consequences. Despite its high morbidity, its etiopathogenesis is incompletely known. A large number of studies suggest that the ability of endometrial implants to grow in ectopic locations may be correlated with the altered immune response towards the endometriotic tissue. There are enough data to show that immune system mediators, such as cytokines and chemokines, are playing key roles in the onset and olso on progression of endometriosis. There are studies that prove the association between endometriosis and autoimmune diseases. The present paper aims to investigate the implications of the immune response in the etiopathogenesis of endometriosis. The study of cellular or humoral immunity deficits, the presence of autoantibodies associated with this condition, can facilitate the understanding of the mechanisms that lead to the appearance and spread of endometriosis. We hope that this information will ultimately provide the basis for the development of new effective approaches in endometriosis management. [ABSTRACT FROM AUTHOR]

Monocytes represent a class of immune cells that play a key role in the innate and adaptive immune response against infections. One mechanism employed by monocytes for sensing foreign antigens is via toll-like receptors (TLRs)--transmembrane proteins that distinguish classes of foreign pathogens, for example, bacteria (TLR4, 5, and 9) vs. fungi (TLR2) vs. viruses (TLR3, 7, and 8). Binding of antigens activates a signaling cascade through TLR receptors that culminate in secretion of inflammatory cytokines. Detection of these cytokines can provide valuable clinical data for drug developers and disease investigations, but this usually requires a large sample volume and can be technically inefficient with traditional techniques such as flow cytometry, enzyme-linked immunosorbent assay, or luminex. This paper describes an approach whereby antibody arrays for capturing cells and secreted cytokines are encapsulated within a microfluidic device that can be reconfigured to operate in serial or parallel mode. In serial mode, the device represents one long channel that may be perfused with a small volume of minimally processed blood. Once monocytes are captured onto antibody spots imprinted into the floor of the device, the straight channel is reconfigured to form nine individually perfusable chambers. To prove this concept, the microfluidic platform was used to capture monocytes from minimally processed human blood in serial mode and then to stimulate monocytes with different TLR agonists in parallel mode. Three cytokines, tumor necrosis factor-a, interleukin (IL)-6, and IL-10, were detected using anti-cytokine antibody arrays integrated into each of the six chambers. We foresee further use of this device in applications such as pediatric immunology or drug/vaccine testing where it is important to balance small sample volume with the need for high information content. [ABSTRACT FROM AUTHOR]

Despite the clinical success of immune checkpoint blockade, only a subset of people exhibits durable responses, suggesting that an alternative immunotherapeutic strategy is required. This paper reported a two-in-one cancer vaccine that targets programmed death ligand 1 (PDL1) that blocks the PD1/PDL1 pathway and also activates antitumor immune response. The PDL1- NitraTh vaccine, which consists of the extracellular domain of PDL1 and nitrated T cell epitope, effectively broke the immune tolerance of PDL1 and elicited PDL1-specific humoral and cellular immunity. The treatment of PDL1-NitraTh exhibited potent antitumor activity. Moreover, immunization of PDL1 vaccine increased the infiltration of tumor lymphocytes and decreased the proportion of Treg cells in tumor tissues, suggesting that the vaccine may remodel the tumor microenvironment. The upregulation of PDL1 in tumor tissues was induced by PDL1-NitraTh vaccine but not in spleen and lymphomas. This upregulation of PDL1 is beneficial to the antitumor activity of PDL1-specific humoral and cellular immunity induced by PDL1-NitraTh. In summary, PDL1-targeted vaccine exhibits potent antitumor activity and may provide an alternative immunotherapy strategy for patients who are not sensitive to PDL1 antibody drugs. [ABSTRACT FROM AUTHOR]

Alpha-synuclein protein is strongly implicated in the pathogenesis Parkinson's disease. Increased expression of α-synuclein due to genetic multiplication or point mutations leads to early onset disease. While α-synuclein is known to modulate membrane vesicle dynamics, it is not clear if this activity is involved in the pathogenic process or if measurable physiological effects of α-synuclein over-expression or mutation exist in vivo. Macrophages and microglia isolated from BAC α-synuclein transgenic mice, which overexpress α-synuclein under regulation of its own promoter, express α-synuclein and exhibit impaired cytokine release and phagocytosis. These processes were affected in vivo as well, both in peritoneal macrophages and microglia in the CNS. Extending these findings to humans, we found similar results with monocytes and fibroblasts isolated from idiopathic or familial Parkinson's disease patients compared to age-matched controls. In summary, this paper provides 1) a new animal model to measure α-synuclein dysfunction; 2) a cellular system to measure synchronized mobilization of α-synuclein and its functional interactions; 3) observations regarding a potential role for innate immune cell function in the development and progression of Parkinson's disease and other human synucleinopathies; 4) putative peripheral biomarkers to study and track these processes in human subjects. While altered neuronal function is a primary issue in PD, the widespread consequence of abnormal α-synuclein expression in other cell types, including immune cells, could play an important role in the neurodegenerative progression of PD and other synucleinopathies. Moreover, increased α-synuclein and altered phagocytosis may provide a useful biomarker for human PD. [ABSTRACT FROM AUTHOR]

This paper presents a mathematical model for immune response against cancer aimed at reproducing emerging phenomena arising from the interactions between tumor and immune cells. The model is stated in terms of integro-differential equations and describes the dynamics of tumor cells, characterized by heterogeneous antigenic expressions, antigen-presenting cells and T-cells. Asymptotic analysis and simulations, developed with an exploratory aim, are addressed to verify the consistency of the model outputs as well as to provide biological insights into the mechanisms that rule tumor-immune interactions. In particular, the present model seems able to mimic the recognition, learning and memory aspects of immune response and highlights how the immune system might act as an additional selective pressure leading, eventually, to the selection for the most resistant cancer clones. [ABSTRACT FROM AUTHOR]

Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs) are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs) and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells) harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS) decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR) signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods. [ABSTRACT FROM AUTHOR]

Immune response to Mycobacterium tuberculosis, the causal agent of tuberculosis, is critical for protection. For many decades, consistent to classical biochemistry, most studies regarding immunity to the tubercle bacilli focused mainly on protein structures. But the atypical, highly impermeable and waxy coat of mycobacteria captured the interest of structural biologists very early, allowing the description of amazing molecules, such as previously unknown carbohydrates or fatty acids of astonishing lengths. From their discovery, cell wall components were identified as important structural pillars, but also as molecular motifs able to alter the human immune response. Recently, as new developments have emerged, classical conceptions of mycobacterial immune modulators have been giving place to unexpected discoveries that, at the turn of the last century, completely changed our perception of immunity vis-`a-vis fat compounds. In this paper, current knowledge about chemical and ultrastructural features of mycobacterial cell-wall is overviewed, with an emphasis on the relationships between cell-wall nonpeptide molecules and immune response. Remarks regarding the potential of these molecules for the development of new tools against tuberculosis are finally discussed. [ABSTRACT FROM AUTHOR]

Major genes could be introgressed into laying hens to attenuate heat stress. However, under cold and/or moderate ambient temperature, these genes might possess different behaviour. The main objective of this study was to evaluate laying performance, immune response, and antioxidant status of native laying hens segregating for naked neck (Na) and frizzle (F) genes under low ambient temperature. Five genotypes were studied: homozygous naked neck (NaNaff), heterozygous naked neck (Nanaff), homozygous frizzle (nanaFF), heterozygous frizzle (nanaFf), and normally feathered (nanaff). The hens were raised under temperature range 22.2-16.7°C. No adverse effect due to ambient temperature was detected in laying performance for naked neck genotypes. Significant decrease in egg weight was recorded in nanaFF genotype compared to the other genotypes leading to significant decrease in egg mass. Significant improvement in shell thickness was associated with Na and F genes. NaNaff genotype had a significantly higher eggshell strength compared to nanaff. Furthermore, Na and F genes improved cellular mediated immune responsiveness, whereas this improvement did not extend to humoral immunity. Birds carrying F gene in homozygous state had a higher total antioxidant activity compared to the remaining genotypes. It could be concluded that the presence of Na and F genes in laying hens raised under low ambient temperature significantly increased shell thickness and, in turn, improved shell strength. Moreover, they greatly enhanced cellular immunity, particularly in heterozygous naked neck status. [ABSTRACT FROM AUTHOR]

In the last twenty years, the general view of the plasma membrane has changed from a homogeneous arrangement of lipids to a mosaic of microdomains. It is currently thought that islands of highly ordered saturated lipids and cholesterol, which are laterally mobile, exist in the plane of the plasma membrane. Lipid rafts are thought to provide a means to explain the spatial segregation of certain signalling pathways emanating from the cell surface. They seem to provide the necessary microenvironment in order for certain specialised signalling events to take place, such as the innate immune recognition. The innate immune system seems to employ germ-lined encoded receptors, called pattern recognition receptors (PRRs), in order to detect pathogens. One family of such receptors are the Toll-like receptors (TLRs), which are the central "sensing" apparatus of the innate immune system. In recent years, it has become apparent that TLRs are recruited into membrane microdomains in response to ligands. These nanoscale assemblies of sphingolipid, cholesterol, and TLRs stabilize and coalesce, forming signalling platforms, which transduce signals that lead to innate immune activation. In the current paper, we will investigate all past and current literature concerning recruitment of extracellular and intracellular TLRs into lipid rafts and how this membrane organization modulates innate immune responses. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of global existence of periodic solutions of a delayed tumor-immune competition model. Also some numerical simulations are given to illustrate the theoretical results [ABSTRACT FROM PUBLISHER]

The overall success of worldwide mass vaccination in limiting the negative effect of the COVID-19 pandemics is inevitable, however, recent SARS-CoV-2 variants of concern, especially Omicron and its sub-lineages, efficiently evade humoral immunity mounted upon vaccination or previous infection. Thus, it is an important question whether these variants, or vaccines against them, induce anti-viral cellular immunity. Here we show that the mRNA vaccine BNT162b2 induces robust protective immunity in K18-hACE2 transgenic B-cell deficient (μMT) mice. We further demonstrate that the protection is attributed to cellular immunity depending on robust IFN-γ production. Viral challenge with SARS-CoV-2 Omicron BA.1 and BA.5.2 sub-variants induce boosted cellular responses in vaccinated μMT mice, which highlights the significance of cellular immunity against the ever-emerging SARS-CoV-2 variants evading antibody-mediated immunity. Our work, by providing evidence that BNT162b2 can induce significant protective immunity in mice that are unable to produce antibodies, thus highlights the importance of cellular immunity in the protection against SARS-CoV-2. Protective immunity against SARS-CoV-2 relies on both antibodies and a T cell dependent response, however, direct experimental evidence for the contribution of cellular immunity is limited. Here authors present a mouse model that is susceptible to SARS-CoV-2 and lacks B cells to demonstrate the emergence of efficient cellular immune response against SARS-CoV-2 upon vaccination or viral challenge. [ABSTRACT FROM AUTHOR]

Tumor growth is influenced by a complex network of interactions between multiple cell types in the tumor microenvironment (TME). These constrained conditions trigger the endoplasmic reticulum (ER) stress response, which extensively reprograms mRNA translation. When uncontrolled over time, chronic ER stress impairs the antitumor effector function of CD8 T lymphocytes. How cells promote adaptation to chronic stress in the TME without the detrimental effects of the terminal unfolded protein response (UPR) is unknown. Here, we find that, in effector CD8 T lymphocytes, RNA‐binding protein CPEB4 constitutes a new branch of the UPR that allows cells to adapt to sustained ER stress, yet remains decoupled from the terminal UPR. ER stress, induced during CD8 T‐cell activation and effector function, triggers CPEB4 expression. CPEB4 then mediates chronic stress adaptation to maintain cellular fitness, allowing effector molecule production and cytotoxic activity. Accordingly, this branch of the UPR is required for the antitumor effector function of T lymphocytes, and its disruption in these cells exacerbates tumor growth. Synopsis: How immune cells invading the tumor microenvironment cope with detrimental stress conditions such as hypoxia and nutrient deprivation remains poorly understood. Here, RNA‐binding protein CPEB4 is shown to mediate a novel branch of transient unfolded protein response (UTR) in CD8 T cells, supporting effector cell viability and antitumor function. Transient acute ER stress promotes CPEB4 translational upregulationCPEB4 mediates chronic ER stress adaptation in CD8 cellsT‐cell effector function requires CPEB4‐mediated chronic ER stress adaptation.CPEB4 promotes T cell‐mediated antitumor immunity in vivo. [ABSTRACT FROM AUTHOR]

Booster vaccination reduces the incidence of severe cases and mortality related to COVID-19, with cellular immunity playing an important role. However, little is known about the proportion of the population that has achieved cellular immunity after booster vaccination. Thus, we conducted a Fukushima cohort database and assessed humoral and cellular immunity in 2526 residents and healthcare workers in Fukushima Prefecture in Japan through continuous blood collection every 3 months from September 2021. We identified the proportion of people with induced cellular immunity after booster vaccination using the T-SPOT.COVID test, and analyzed their background characteristics. Among 1089 participants, 64.3% (700/1089) had reactive cellular immunity after booster vaccination. Multivariable analysis revealed the following independent predictors of reactive cellular immunity: age < 40 years (adjusted odds ratio: 1.81; 95% confidence interval: 1.19–2.75; p-value: 0.005) and adverse reactions after vaccination (1.92, 1.19–3.09, 0.007). Notably, despite IgG(S) and neutralizing antibody titers of ≥500 AU/mL, 33.9% (349/1031) and 33.5% (341/1017) of participants, respectively, did not have reactive cellular immunity. In summary, this is the first study to evaluate cellular immunity at the population level after booster vaccination using the T-SPOT.COVID test, albeit with several limitations. Future studies will need to evaluate previously infected subjects and their T-cell subsets. [ABSTRACT FROM AUTHOR]

Porcine deltacoronavirus (PDCoV) causes diarrhea and vomiting in neonatal piglets worldwide and has the potential for cross-species transmission. Therefore, virus-like particles (VLPs) are promising vaccine candidates because of their safety and strong immunogenicity. To the best of our knowledge, the present study reported for the first time the generation of PDCoV VLPs using a baculovirus expression vector system, and electron micrograph analyses revealed that PDCoV VLPs appeared as spherical particles with a diameter similar to that of the native virions. Furthermore, PDCoV VLPs effectively induced mice to produce PDCoV-specific IgG and neutralizing antibodies. In addition, VLPs could stimulate mouse splenocytes to produce high levels of cytokines IL-4 and IFN-γ. Moreover, the combination of PDCoV VLPs and Freund's adjuvant could improve the level of the immune response. Together, these data showed that PDCoV VLPs could effectively elicit humoral and cellular immunity in mice, laying a solid foundation for developing VLP-based vaccines to prevent PDCoV infections. [ABSTRACT FROM AUTHOR]

Background Selected cytokines produced by allergen specific CD4+ T cells from atopic individuals contribute to both the specific and non-specific effector mechanisms of the allergic immune response. The chemokine family of cytokines and tumour necrosis factor (TNF)-α are leucocyte regulatory and proinflammatory molecules. The chemokines include interleukin (IL)-8 and the RANTES/SIS cytokines. Objective There bas been no systematic survey of chemokine production in T-cell subtypes. Because of their wide range of biological properties, it might be expected that they would be closely regulated by T cells. This paper illustrates one way (through the characterization of T-cell clones) these questions might be addressed. Methods Northern blot analysis was used to quantitate steady state transcription of selected cytokine genes and enzyme linked immunosorbent assay (ELISA) was used to quantitate soluble product. Results mRNA expression of the chemokines (IL-8. HuMIP-lα and HuMIP-lβ) and TNFα is upregulated in TH2-like cloned house dust mite reactive human CD4+ T cells under conditions of activation and during the induction phase of anergy. Although the development of anergy superinduces mRNA for both IL-8 and TNFα, protein production is low compared with that released during activation. In contrast, RANTES, a chemoattractant for CD4+ /CD45RO+ memory T cells, eosinophils and basophils, is constitutively expressed at the RNA level by the T cells and not modulated by signals of activation and anergy induction. The production of IL-2, IL-4 and IL-5 mRNA and proteins during the induction of anergy peaks at 2h after stimulation, whereas the kinetics following activation of the T cells is delayed in comparison. Conclusion These data show that the induction of the anergic state coincides with post-transcriptional regulation of selected cytokine genes. Further study of these phenomena will impact on our understanding of the mechanisms of induction of anergy and the regulation of allergic immune responses in desensitization. [ABSTRACT FROM AUTHOR]

Cellular immune responses are important in the recovery from human cytomegalovirus (HCMV) infection. However, little is known about the CD4+ T cell response and the target antigens (Ag) recognized. In this paper, we have analysed the proliferative T cell response of healthy HCMV seropositive (HCMV+) blood donors to recombinant immediate-early proteins expressed in transfected astrocytoma cells and to total HCMV Ags expressed in infected astrocytoma cells. We found that CD4+ T cells were the major cell population that proliferated in the presence of IE or total HCMV Ags. Among healthy HCMV seropositive blood donors with anti-HCMV specific proliferative response, 33-44% also responded to IE Ags. Moreover, in high responders, the precursor frequencies of cells which proliferated in the presence of total HCMV, IE, or IE1 Ags were high (1/103 to 1/255, 1/2785 to 1/7744 and 1/5190 to 1/13531, respectively). In some donors, the anti-IE response was variable over time, whereas the anti-total HCMV Ags response remained constant, which suggests regulation of the anti-IE response in immunocompetent subjects. Our results suggest that the CD4+ anti-IE1 response represents a significant part of the anti-HCMV proliferative response, both at the population level, and within individual immune systems. [ABSTRACT FROM AUTHOR]

We have previously shown that two distinct mouse placental fractions (PF) are potent immunomodulators in vivo. A 40 kDa PF induces a marked decrease of plaque forming cell (PFC) responses, while a 60 kDa PF increases them. Both effects are specific for the priming antigen. In the present study, these two PF are assayed on a cell-mediated response to allogeneic cells, i.e. in a local graft-versus-host reaction (LGVHR). Mice were primed with allogeneic cells in the presence of various amounts of the 40 kDa or 60 kDa PF, or liver extract (LE) as control. Six days later, their spleen cells were injected into the footpads of F1 recipients. Precise dose-response curves were established and the kinetics of the GVH response were carefully followed. Parallel with the modulation of PFC responses, the 40 kDa PF caused a potent inhibition of the LGVHR, while the 60 kDa PF greatly enhanced it. Both effects were specific for the alloantigens injected with the PF. Furthermore, we showed that these modulations were observed whatever the intensity of the GVH reaction, which varied according to the number of primed spleen cells transferred. This report also demonstrates that these PF can be greatly enriched by package over affinity columns made of insolubilized lectins. The 40 kDa PF is retained on and can be eluted from columns of insolubilized concanavalin A (Con A) or wheat germ agglutinin (WGA), which indicates that it is a glycoprotein. Conversely, the 60 kDa PF does not bind to any of the above lectins and is probably not a glycoprotein. This biochemical purification step is also a good procedure for obtaining an even cleaner separation of the two fractions from each other. Thus, this paper demonstrates that both PF have important regulatory, properties on specific cellular immune responses. [ABSTRACT FROM AUTHOR]

We demonstrated the efficacy of a long- term cultured cytotoxic T-lymphocyte line, CTLL-D4, on tumour growth inhibition using athymic nude mice as recipients. CTLL-D4, specific for a unique surface determinant on a radiation-induced leukaemia RL♂1 of BALB/c origin, was obtained from the limiting dilution culture of MLTC cells performed between spleen cells of a CS6F1-nu/ + mouse immunized in vivo and RL♂1 stimulator cells, and cultured for several months in the absence of added TCGF as described in our preceding paper (Kuribayashi, 1985). The specific inhibition of tumour growth by CTLL-D4 was demonstrated both in Winn-type neutralization assay and in systemic transfer experiments. A subcutaneous inoculation of the mixture of CTLL-D4 and RL♂1 cells resulted in the complete inhibition of tumour growth, even at the effector to tumour cell ratio of 1 : 1, whereas non-cytolytic D4f, which was self-Ia antigen(s)-reactive, composed entirely of Lyt-l + 23- T cells and derived originally from CTLL-D4 but completely lost its cytotoxic activity during culture with the irradiated syngeneic feeder cells alone, had no inhibitory effect at all. In the adoptive transfer studies, the subcutaneously established tumours were rejected by the single i.v. transfer of 2 × 107 CTLL-D4 cells into CB6F1-nu/nu mice. However, D4f was ineffective again in this systemic transfer system. When the effect of CTLL-D4 cells on tumour rejection in vivo was compared to that of non-cultured spleen cells hyperimmunized with RL♂1 cells, the former exhibited more rapid rejection in nude mice after i.v. transfer than the latter did, suggesting that CTLL-D4 cells also attack the tumour cells much more effectively as effectors in vivo. Thus, it is conceivable that CTLs are mainly involved in tumour rejection in this adoptive transfer system using RL♂ 1 tumour cells and athymic nude mice. [ABSTRACT FROM AUTHOR]

This paper describes the induction of delayed-type hypersensitivity (DH) in the mouse and guinea-pig to haptenated liposomes. The tripeptide- enlarged hapten 3-(p-azobenzenearsonate)-N-acetyl- L-tyrosylglycylglycine (A) was coupled to phosphatidylethanolamine (PE) and incorporated into liposomal membranes (A PE-liposomes). In mice DH was measured as footpad swelling and in guinea pigs by skin testing. To induce hapten A-specific DH in mice with A-PE- liposomes the application of the cationic, surface- active lipid, dimethyl dioctadecyl ammonium bromide (DDA) was necessary. The use of Freund's complete adjuvant (FCA) did not result in the induction of DH to hapten A. In guinea-pigs, however, FCA and DDA had equally good adjuvant properties in the induction of DH. The time course of the DH and the optimal time interval between immunization and elicitation were determined for the mouse system. Also, the effect of dose and epitope density was studied in that system. Cyclophosphamide treatment, before immunizing mice with A-PE-liposomes and DDA, resulted in greatly impaired DH, probably caused by the short lifetime of the integrity of liposomes after intracutaneous administration to mice. The results make it very likely that presentation of hapten A in a liposomal or micellar structure is required to induce a cellular immune response to this hapten in mice. [ABSTRACT FROM AUTHOR]

The experiments described in this paper extend the observations of previous work in vitro demonstrating a decrease in the frequency of antigenreactive units specific for horse RBC in spleen cells from mice primed with KLH. It was observed that the addition of lymphoid cells having T-cell function reconstituted the anti-HRBC response to normal values. Significant enhancement of the response beyond the normal values could be evoked using two dissimilar methods, (i) addition of allogeneic thymus cells, and (ii) restimulation in vitro with the priming antigen. The latter type enhancement was elicited by the addition of small doses of KLH to cultures of spleen cells from mice recently primed with KLH, including cultures otherwise demonstrating antigen-induced suppression. The stimulus required to enhance the response to HRBC in these cultures was specific for the priming antigen, KLH. These results are discussed in the light of current theories of 'antigenic competition' and specific heterologous enhancement. [ABSTRACT FROM AUTHOR]

Immune responsiveness to the streptotoccal group polysaccharides at the clonal level can conveniently be monitored by analytical isoelectric focusing combined witb autoradiography. The parameters investigated in this paper can be summarized as follows: [l] Within the first week after injection antistreptococcal polysaccbaride responses art characterized by IgM antibodies, followed by subclass restriction in Balb/c mice to IgG2a antihodies. [2] The clonal pattern of specific IgG2a antibodies established in the second week after inimunization does not change within the following 6 weeks. [3] Persistence of a specific response pattern established within a primary immunization course holds for Balb/c mice and rabbits for as long as 12 to 13 months. [4] Repeated immunization courses in mice and rabbits maintain established clonal antibody patterns in toto. Temporal variations of clonal expression are generally quantitative rather than qualitative. B-cell memory within this system is therefore stable and long-lived. [ABSTRACT FROM AUTHOR]

Protective immunity against COVID-19 is orchestrated by an intricate network of innate and adaptive anti-viral immune responses. Several vaccines have been rapidly developed to combat the destructive effects of COVID-19, which initiate an immunological cascade that results in the generation of neutralizing antibodies and effector T cells towards the SARS-CoV-2 spike protein. Developing optimal vaccine-induced anti-SARS- CoV-2 protective immunity depends on a fully competent immune response. Some evidence was gathered on the effects of vaccination outcomes in immunocompromised adult individuals. Nonetheless, protective immunity elicited by the Pfizer Biontech BNT162b2 vaccine in immunocompromised adolescents received less attention and was mainly focused on the antibody response and their neutralization potential. The overall immune response, including T-cell activities, was largely understudied. In this study, we characterized the immune response of vaccinated immunocompromised adolescents. We found that immunocompromised adolescents, which may fail to elicit a humoral response and develop antibodies, may still develop cellular T-cell immunity towards SARS-CoV-2 infections. Furthermore, most immunocompromised adolescents due to genetic disorders or drugs (Kidney and liver transplantation) still develop either humoral, cellular or both arms of immunity towards SARS-CoV-2 infections. We also demonstrate that most patients could mount a cellular or humoral response even after six months post 2nd vaccination. The findings that adolescents immunocompromised patients respond to some extent to vaccination are promising. Finally, they question the necessity for additional vaccination boosting regimens for this population who are not at high risk for severe disease, without further testing of their post-vaccination immune status. [ABSTRACT FROM AUTHOR]

Background: Data on SARS-CoV-2 mRNA vaccine immunogenicity in people living with human immunodeficiency virus (PLWH) and discordant immune response (DIR) are currently limited. Therefore, we compare the immunogenicity of these vaccines in DIR and immunological responders (IR). Methods: A prospective cohort that enrolled 89 participants. Finally, 22 IR and 24 DIR were analyzed before vaccination (T0), one (T1) and six months (T2) after receiving BNT162b2 or mRNA-1273 vaccine. Additionally, 10 IR and 16 DIR were evaluated after a third dose (T3). Anti-S-RBD IgG, neutralizing antibodies (nAb), neutralization activity, and specific memory B cells were quantified. Furthermore, specific CD4+ and CD8+ responses were determined by intracellular cytokine staining and polyfunctionality indexes (Pindex). Results: At T1, all participants developed anti-S-RBD. 100% IR developed nAb compared to 83.3% DIR. Spike-specific B cells were detected in all IR and 21/24 DIR. Memory CD4+ T cells responded in 5/9 IR and 7/9 DIR, mainly based on the expression of IFN-γ and TNF-α, with a higher Pindex in DIR. Memory CD8+ T cells responded in only four participants in each group. At T2, anti-S-RBD and nAb titers were higher in DIR than in IR. In both groups, there was an increase in specific B memory cells, higher in DIR. Six IR and five DIR maintained a specific memory CD4+ response. Memory CD8+ response was preserved in IR but was lost in DIR. In a multivariate linear regression analysis, receiving mRNA-1273 instead of BNT162b2 played a prominent role in the results. Conclusions: Our data suggest that PLWH with DIR can mount an immune response similar to those with higher CD4+, provided they receive the mRNA-1273 vaccine instead of others less immunogenic. [ABSTRACT FROM AUTHOR]

Introduction: The differential immune responses after two additional BNT162b2 (BNT) booster doses between ChAdOx1 nCoV-10 (ChAd)-primed and BNTprimed groups have not been elucidated. The aim of this study was to compare vaccine-induced humoral and cellular immune responses and evaluate breakthrough infection between the two vaccination strategies. Methods: In 221 healthy subjects (111 in the ChAd group), longitudinal immune responses weremonitored at 3, 4, and 6 months after the 2nd dose and 1, 3, and 6 months after the 3rd dose. Humoral immunity was measured by two fully automated chemiluminescent immunoassays (Elecsys and Abbott) and a surrogate virus neutralization test (sVNT). Cellular immunity was assessed by two interferon-g (IFN-g) release assays (QuantiFERON SARS-CoV-2 and Covi-FERON). Results: After the 2nd dose of BNT vaccination, total antibody levels were higher in the ChAd group, but IgG antibody and sVNT results were higher in the BNT group. Following the 3rd dose vaccination, binding antibody titers were significantly elevated in both groups (ChAD-BNT; 15.4 to 17.8-fold, BNT-BNT; 22.2 to 24.6-fold), and the neutralizing capacity was increased by 1.3-fold in both cohorts. The ChAd-BNT group had lower omicron neutralization positivity than the BNT-BNT group (P = 0.001) at 6 months after the 3rd dose. Cellular responses to the spike antigen also showed 1.7 to 3.0-fold increases after the 3rd dose, which gradually declined to the levels equivalent to before the 3rd vaccination. The ChAd cohort tended to have higher IFN-g level than the BNT cohort for 3-6 months after the 2nd and 3rd doses. The frequency of breakthrough infection was higher in the ChAd group (44.8%) than in the BNT group (28.1%) (P = 0.0219). Breakthrough infection induced increased humoral responses in both groups, and increase of cellular response was significant in the ChAd group. Discussion: Our study showed differential humoral and cellular immune responses between ChAd-BNT-BNT heterologous and BNT-BNT-BNT homologous vaccination cohorts. The occurrence of low antibody levels in the ChAd-primed cohort in the humoral immune response may be associated with an increased incidence of breakthrough infections. Further studies are needed on the benefits of enhanced cellular immunity in ChAd-primed cohorts. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46–23.13), 11.12 (2.74–45.09), and 20.70 (5.05–84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27–25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1. [ABSTRACT FROM AUTHOR]

The present study focused on demonstrating the induction of humoral and cell-mediated immunity through the establishment of a cytokine network. We hypothesized the anti-inflammatory, pro-inflammatory, and IgE antibody levels after vaccination with lyophilized recombinant HBsAg-loaded docosahexaenoic acid nanovesicles (LRPDNV), and the efficacy compared well with standard commercial recombinant hepatitis B vaccine. The cytokine network was efficiently regulated by striking a balance between pro-inflammatory cytokines IL-6, IL-8R, and IL-12 and anti-inflammatory cytokines such as IL-2, IL-4, IL-10, and IFN-γ immune response on the 14th and 30th day after primary and booster immunization. The acute phase protein CRP level was increased due to IL-6 after immunizing with LRPDNV. On the other hand, the IgE level was not significantly increased to induce any allergic reactions after immunization with LRPDNV. The study concluded that after immunizing with LRPDNV, a significant immunological response was established, implying that DHA nanovesicles have significant potential as an adjuvant method for delivering recombinant HBsAg protein. On the other hand, following immunization with LRPDNV, the IgE level was not noticeably elevated enough to cause any adverse reactions. The study concludes that a robust immune response was developed after immunizing with LRPDNV and suggests that DHA nanovesicles have much potential to deliver recombinant HBsAg protein. [ABSTRACT FROM AUTHOR]