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Substantial progress has been made with cancer immunotherapeutic strategies in recent years, most of which mainly rely on enhancing the T cell response. However, sufficient tumor antigen information often cannot be presented to T cells, resulting in a failed effector T cell response. The innate immune system can effectively recognize tumor antigens and then initiate an adaptive immune response. Here, we developed a spontaneous multifunctional hydrogel (NOCC-CpG/OX-M, Ncom Gel) vaccine to amplify the innate immune response and harness innate immunity to launch and maintain a powerful adaptive immune response. Methods: Ncom Gel was formed by a Schiff base reaction between CpG-modified carboxymethyl chitosan (NOCC-CpG) and partially oxidized mannan (OX-M). The effects of the Ncom Gel vaccine on DCs and macrophages in vitro and antigen-specific humoral immunity and cellular immunity in vivo were studied. Furthermore, the antitumor immune response of the Ncom Gel vaccine and its effect on the tumor microenvironment were evaluated. Results: The Ncom Gel vaccine enhanced antigen presentation to T cells by facilitating DC uptake and maturation and inducing macrophages to a proinflammatory subtype, further leading to a T cell-mediated adaptive immune response. Moreover, the innate immune response could be amplified via the promotion of antigen-specific antibody production. The Ncom Gel vaccine reversed the tumor immune microenvironment to an inflamed phenotype and showed a significant antitumor response in a melanoma model. Conclusions: Our research implies the potential application of injectable hydrogels as a platform for tumor immunotherapy. The strategy also opens up a new avenue for multilayered cancer immunotherapy.

Background The reliable detection of T cell response to COVID-19 or COVID-19 vaccination is important for individual patient care and for monitoring the immune response e.g. in COVID-19 vaccine trials in a standardized fashion. Objectives and study design We used blood samples from health care workers (HCW) with or without history of COVID-19 to define test accuracy of a novel interferon-γ release assay (IGRA). For a real-life performance evaluation, we analysed interferon-γ response to complete COVID-19 vaccination in HCW receiving homologous or heterologous vaccination regimens and in patients receiving immunosuppressive or immune modulating therapies. Results The assay had a specificity of 100%. Sensitivity of the IGRA to detect past infection was 72.2% after infection more than 5 months ago and 93.8% after COVID-19 up to 5 months ago. Quantitative results showed significant differences between first and second vaccine dose, but no difference between homologous and heterologous vaccination regimen. Immunocompromised patients often had no immune response or isolated T cell or antibody response to complete vaccination. Conclusions The novel IGRA proved to be a highly specific tool to detect SARS-CoV-2 specific T cell response to COVID-19 as well as COVID-19 vaccination, with sensitivity getting lower over time. In perspective, it may serve as a standardized tool in COVID-19 vaccine trials and in clinical care of immunosuppressed patients., Graphical abstract Image, graphical abstract

Thermal injury (TI) with septic complications continues to be a serious clinical problem. One of the main concerns in such patients is immunosuppression related to functional derangements in intestinal CD4+ T lymphocytes. Extensive previous studies in thermal injury/septic patients and animal models of thermal injury/sepsis have shown decreased responsiveness of intestinal CD4+ T cells to antigen/mitogen. This hyporesponsiveness could significantly contribute to increase injured host susceptibility to pathogens including those translocating from host's gut lumen. Our previous studies indicated that while thermal injury or sepsis alone lead to suppressed proliferation and IL-2 production of intestinal CD4+ T cells, this study showed a substantial deletion via apoptosis of the Mesenteric Lymph Nodes (MLN) CD4+ T cells. Hence, thermal injury-plus-sepsis contributes not only to suppressed CD4+ T proliferation/IL-2 production but also to a substantial modulation of CD4+ T cell survivability. These findings allow us to conclude that while thermal injury alone can produce attenuated cell mediated responses without an overt change in CD4+ T cell survival, thermal injury with septic complications causes CD4+ T cell death and an irreversible loss of cell-mediated responses. The latter happening could be responsible for high morbidity and mortality in the injured host afflicted with thermal injury plus a critical infection.

We propose and study a new mathematical model of the human immunodeficiency virus (HIV). The main novelty is to consider that the antibody growth depends not only on the virus and on the antibodies concentration but also on the uninfected cells concentration. The model consists of five nonlinear differential equations describing the evolution of the uninfected cells, the infected ones, the free viruses, and the adaptive immunity. The adaptive immune response is represented by the cytotoxic T-lymphocytes (CTL) cells and the antibodies with the growth function supposed to be trilinear. The model includes two kinds of treatments. The objective of the first one is to reduce the number of infected cells, while the aim of the second is to block free viruses. Firstly, the positivity and the boundedness of solutions are established. After that, the local stability of the disease free steady state and the infection steady states are characterized. Next, an optimal control problem is posed and investigated. Finally, numerical simulations are performed in order to show the behavior of solutions and the effectiveness of the two incorporated treatments via an efficient optimal control strategy., This is a preprint of a paper whose final and definite form is with 'Discrete and Continuous Dynamical Systems - Series S' (DCDS-S), ISSN 1937-1632 (print), ISSN 1937-1179 (online), available at [http://aimsciences.org/journal/1937-1632]. Paper Submitted 01-June-2019; Revised 10-May-2021; Accepted 21-May-2021. arXiv admin note: text overlap with arXiv:1801.10048

This paper studies an (n + 4)-dimensional nonlinear viral infection model that characterizes the interactions of the viruses, susceptible host cells, n-stages of infected cells, CTL cells and B cells. Both viral and cellular infections have been incorporated into the model. The well-posedness of the model is justified. The model admits five equilibria which are determined by five threshold parameters. The global stability of each equilibrium is proven by utilizing Lyapunov function and LaSalle's invariance principle. The theoretical results are illustrated by numerical simulations.

This paper investigates an adaptive immunity HIV infection model with three types of distributed time delays. The model describes the interaction between healthy CD4+T cells, silent infected cells, active infected cells, free HIV particles, Cytotoxic T lymphocytes (CTLs) and antibodies. The healthy CD4+T cells can be infected when they contacted by free HIV particles or silent infected cells or active infected cells. The incidence rates of the healthy CD4+T cells with free HIV particles, silent infected cells, and active infected cells are given by general functions. Moreover, the production/proliferation and removal/death rates of the virus and cells are represented by general functions. The model is an improvement of the existing HIV infection models which have neglected the infection due to the incidence between the silent infected cells and healthy CD4+T cells. We show that the model is well posed and it has five equilibria and their existence are governed by five threshold parameters. Under a set of conditions on the general functions and the threshold parameters, we have proven the global asymptotic stability of all equilibria by using Lyapunov method. We have illustrated the theoretical results via numerical simulations. We have studied the effect of cell-to-cell (CTC) transmission and time delays on the dynamical behavior of the system. We have shown that the inclusion of time delay can significantly increase the concentration of the healthy CD4+ T cells and reduce the concentrations of the infected cells and free HIV particles. While the inclusion of CTC transmission decreases the concentration of the healthy CD4+ T cells and increases the concentrations of the infected cells and free HIV particles.

The objective of this paper is to investigate a mathematical model describing the infection of hepatitis B virus (HBV) in intrahepatic and extrahepatic tissues. Additionally, the model includes the effect of the cytotoxic T cell (CTL) immunity, which is described by a linear activation rate by infected cells. The positivity and boundedness of solutions for non-negative initial data are proven, which is consistent with the biological studies. The local stability of the equilibrium is established. In addition to this, the global stability of the disease-free equilibrium and the endemic equilibrium is fulfilled by using appropriate Lyapanov functions. Finally, numerical simulations are performed to support our theoretical findings. It has been revealed that the fractional-order derivatives have no influence on the stability but only on the speed of convergence toward the equilibria.

This paper studies the global dynamics of a general diffusive hepatitis B virus (HBV) infection model. The model includes both enveloped viruses and DNA containing capsids. Two immune responses are recruited to attack the virus and infected hepatocytes. These are the cytotoxic T-lymphocytes (CTL) which kill the infected liver cells, and B cells which send antibodies to attack the virus. The non-negativity and boundedness of the solutions are discussed. The existence of spatially homogeneous equilibrium points is examined. The global stability of all possible equilibrium points is proved by choosing suitable Lyapunov functionals. Some numerical simulations are performed to enhance the theoretical results and present the behavior of solutions in space and time.

In this paper, the dynamical behaviors for a five-dimensional virus infection model with diffusion and two delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses and a general incidence function are investigated. The reproduction numbers for virus infection, antibody immune response, CTL immune response, CTL immune competition and antibody immune competition, respectively, are calculated. By using the Lyapunov functionals and linearization methods, the threshold conditions on the global stability of the equilibria for infection-free, immune-free, antibody response, CTL response and antibody and CTL responses, respectively, are established if the space is assumed as homogeneous. When the space is inhomogeneous, the effects of diffusion, intracellular delay and production delay are obtained by the numerical simulations.

A novel coronavirus disease (COVID-19) appeared in Wuhan, China in December 2019 and spread around the world at a rapid pace, taking the form of pandemic. There was an urgent need to look for the remedy and control this deadly disease. A new strain of coronavirus called Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was considered to be responsible for COVID-19. Novel coronavirus (SARS-CoV-2) belongs to the family of coronaviruses crowned with homotrimeric class 1 fusion spike protein (or S protein) on their surfaces. COVID-19 attacks primarily at our throat and lungs epithelial cells. In COVID-19, a stronger adaptive immune response against SARS-CoV-2 can lead to longer recovery time and leads to several complications. In this paper, we propose a mathematical model for examining the consequence of adaptive immune responses to the viral mutation to control disease transmission. We consider three populations, namely, the uninfected epithelial cells, infected cells, and the SARS-CoV-2 virus. We also take into account combination drug therapy on the dynamics of COVID-19 and its effect. We present a fractional-order model representing COVID-19/SARS-CoV-2 infection of epithelial cells. The main aim of our study is to explore the effect of adaptive immune response using fractional order operator to monitor the influence of memory on the cell-biological aspects. Also, we have studied the outcome of an antiviral drug on the system to obstruct the contact between epithelial cells and SARS-CoV-2 to restrict the COVID-19 disease. Numerical simulations have been done to illustrate our analytical findings.