Synergistic Therapeutic Effects of Probiotic Lactobacillus casei TD-2 Consumption on GM-CSF-Induced Immune Responses in a Murine Model of Cervical Cancer.

We perceive the potential of combined immunotherapy for the synergistic treatment of human papillomavirus (HPV)-associated tumors. So, the tumor inhibiting effects of combination of L. casei TD2a and GM-CSF on the TC-1 growth were evaluated In Vivo using lymphocyte proliferation, lymphocyte cytotoxicity, splenocyte, and tumor cytokine assays. The results showed that tumor inhibition in transplanted mice in the GM-CSF combined with probiotic L. casei group was significantly higher than that observed in the other groups excluding GM-CSF group whose tumor inhibition effect was considerable. The findings also indicated that the combined group could generate tumor-specific cytolytic and splenocyte proliferative responses. The levels of IFN-γ, IL-4, and IL-12 after treating with GM-CSF combined with probiotic L. casei were significantly higher than those of other groups. The intratumoral Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) was also significantly increased in the combined group. Tumor analysis further showed that the combined group decreased the accumulation of IL-10 in the tumor microenvironment of treated mice. Furthermore, tumor volume analysis demonstrated that combination group and even GM-CSF suppress tumor growth. Our findings showed that the combination of GM-CSF and probiotic results in improved tumor suppression against HPV-associated tumors and stimulates enhancement of specific antitumor immune responses.

Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches.

Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

Role of γδ T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches.

BACKGROUND: Influenza virus infection is among the most detrimental threats to the health of humans and some animals, infecting millions of people annually all around the world and in many thousands of cases giving rise to pneumonia and death. All those health crises happen despite previous and recent developments in anti-influenza vaccination, suggesting the need for employing more sophisticated methods to control this malign infection. Main body The innate immunity modules are at the forefront of combating against influenza infection in the respiratory tract, among which, innate T cells, particularly gamma-delta (γδ) T cells, play a critical role in filling the gap needed for adaptive immune cells maturation, linking the innate and adaptive immunity together. Upon infection with influenza virus, production of cytokines and chemokines including CCL3, CCL4, and CCL5 from respiratory epithelium recruits γδ T cells at the site of infection in a CCR5 receptor-dependent fashion. Next, γδ T cells become activated in response to influenza virus infection and produce large amounts of proinflammatory cytokines, especially IL-17A. Regardless of γδ T cells' roles in triggering the adaptive arm of the immune system, they also protect the respiratory epithelium by cytolytic and non-cytolytic antiviral mechanisms, as well as by enhancing neutrophils and natural killer cells recruitment to the infection site. CONCLUSION: In this review, we explored varied strategies of γδ T cells in defense to influenza virus infection and how they can potentially provide balanced protective immune responses against infected cells. The results may provide a potential window for the incorporation of intact or engineered γδ T cells for developing novel antiviral approaches or for immunotherapeutic purposes.

The immunomodulatory effects of probiotics on respiratory viral infections: A hint for COVID-19 treatment?

Respiratory virus infections are among the most prevalent diseases in humans and contribute to morbidity and mortality in all age groups. Moreover, since they can evolve fast and cross the species barrier, some of these viruses, such as influenza A and coronaviruses, have sometimes caused epidemics or pandemics and were associated with more serious clinical diseases and even mortality. The recently identified Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a Public Health Emergency of International concern and has been associated with rapidly progressive pneumonia. To ensure protection against emerging respiratory tract infections, the development of new strategies based on modulating the immune responses is essential. The use of probiotic components has substantially increased due to their effects on immune responses, in particular on those that occur in the upper/lower respiratory tract. Superinduction of inflammatory reaction, known as a cytokine storm, has been correlated directly with viral pneumonia and serious complications of respiratory infections. In this review, probiotics, as potential immunomodulatory agents, have been proposed to improve the host's response to respiratory viral infections. In addition, the effects of probiotics on different aspects of immune responses and their antiviral properties in both pre-clinical and clinical contexts have been described in detail.

Evaluation of the antitumor immune responses of probiotic Bifidobacterium bifidum in human papillomavirus-induced tumor model.

As of present, a number of studies have shown anti-cancer effects of different strains of probiotics, but the precise host immunological mechanisms of these antitumor effects remain unclear. Thus, the aim of current study was to investigate the preventive-therapeutic effects of oral versus intravenous administration of probiotic Bifidobacterium bifidum on immune response and tumor growth of C57BL/6 mice bearing transplanted TC-1 cell of human papillomavirus (HPV)-related tumor, expressing HPV-16 E6/E7 oncogenes. Our major findings are that the intravenous or oral administration of Bifidobacterium bifidum effectively induces antitumor immune responses and inhibits tumor growth in mice. Compared to oral route only, intravenous administration of probiotic Bifidobacterium bifidum into tumor-bearing mice leads to the activation of tumor-specific IL-12 and IFN-γ, lymphocyte proliferation, CD8+ cytolytic responses that control and eradicate tumor growth. These observations meant intravenous administration of probiotics is an effective anticancer approach through modulation of the immune system. The potential of probiotic Bifidobacterium bifidum as an immunomodulator in the treatment of cervical cancer could be further explored.

Immunomodulatory and prophylactic effects of Bifidobacterium bifidum probiotic strain on influenza infection in mice.

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.