Cellular Immune Effects Research Articles

A Magnetically Driven Biodegradable Microsphere with Mass Production Capability for Subunit Vaccine Delivery and Enhanced Immunotherapy.

Subunit vaccines have emerged as a promising strategy in immunotherapy for combating viral infections and cancer. Nevertheless, the clinical application of subunit vaccines is hindered by limitations in antigen delivery efficiency, characterized by rapid clearance and inadequate cellular uptake. Here, a novel subunit vaccine delivery system utilizing ovalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable gelatin methacryloyl (GelMA) microspheres was proposed to enhance the efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres, denoted as OMGMs, can be navigated through magnetic fields to deliver subunit vaccines into the lymphatic system efficiently. Moreover, the biodegradable OMGMs enabled the sustained release of subunit vaccines, concentrating OVA around lymph nodes and enhancing the efficacy of induced immune response. OMGMs were produced through a microfluidic droplet generation technique, enabling mass production. In murine models, OMGMs successfully accumulated antigens in lymph nodes abundant in antigen-presenting cells, leading to enhanced cellular and humoral immunity and pronounced antitumor effects with a single booster immunization. In conclusion, these findings highlight the promise of OMGMs as a practical subunit vaccination approach, thus addressing the limitations associated with antigen delivery efficiency and paving the way for advanced immunotherapeutic strategies.

Immunogenicity Analysis and Identification of Potential T-Cell Epitopes in C129R Protein of African Swine Fever Virus.

The highly conserved C129R protein of AFSV was utilized in the development of an ASFV recombinant adenovirus vaccine, demonstrating strong immunogenicity. In this study, we immunized 6-week-old female C57BL/6J mice via subcutaneous injection with 10 μg of purified C129R protein. Humoral and cellular immune effects were assessed using ELISA, flow cytometry, and ELISpot assays. Additionally, 19 peptides of the C129R protein were synthesized and screened for the use of bioinformatics. Positive T-cell epitopes were screened using ELISpot. The results indicated a higher proportion of CD4+ and CD8+ T lymphocytes in immunized mice compared to control mice. ELISA analysis revealed a serum titer of approximately 1:1, 638, 400 in the experimental group of mice. Additionally, peptides C11(53-61aa), C14(81-89aa), C16(97-105aa), and C18(116-124aa) from the C129R protein were able to activate mice spleen lymphocytes to produce IFN-γ. These findings suggest that the C129R protein significantly enhances both humoral and cellular immunity in immunized mice. Moreover, peptides C11, C14, C16, and C18 may serve as potential T-cell epitopes for the C129R protein. These results lay the groundwork for the further exploration of ASFV C129R protein and the identification of novel ASF vaccine antigens.

EFFECT OF STRATIFIED DOSE OF NOREPINEPHRINE ON CELLULAR IMMUNE RESPONSE IN PATIENTS WITH SEPTIC SHOCK AND THE CONSTRUCTION OF A PROGNOSTIC RISK MODEL.

Objective: To explore the effect of a stratified dose of norepinephrine (NE) on cellular immune response in patients with septic shock, and to construct a prognostic model of septic shock. Methods: A total of 160 patients with septic shock (B group) and 58 patients with sepsis (A group) were given standard cluster therapy. Patients with septic shock were divided into four groups (B1-B4 groups: 0.01-0.2, 0.2-0.5, 0.5-1.0, and >1 μg/kg/min) according to the quartile method of the early (72 h) time-weighted average dose of NE and clinical application. The cellular immune indexes at 24 h (T0) and 4-7 days (T1) after admission were collected. The difference method was used to explore the effect of NE stratified dose on cellular immune effect in patients with septic shock. A multivariate COX proportional risk regression model was used to analyze the independent prognostic risk factors, and a prognostic risk model was constructed. Results: The differences of ΔIL-1β, ΔIL-6, ΔIL-10, absolute value difference of T lymphocyte (ΔCD3+/CD45+#) and Th helper T cell (ΔCD3+ CD4+/CD45+#), CD64 infection index difference, ΔmHLA-DR, regulatory T lymphocyte ratio difference (ΔTregs%) between group A, B1, B2, B3, and B4 were statistically significant ( P < 0.05). There was a nonlinear relation between the stratified dose of NE and ΔIL-6, ΔIL-10, ΔCD3+/CD45+#, ΔmHLA-DR%. The threshold periods of NE-induced proinflammatory and anti-inflammatory immune changes were 0.3-0.5 μg/kg/min. Multivariate COX model regression analysis showed that age, nutritional patterns, weighted average dose of norepinephrine, IL-6, absolute value of T lymphocytes, and mHLA-DR were independent risk factors affecting the prognosis of patients with septic shock ( P < 0.05). The prognostic risk model was constructed (AUC value = 0.813, 95% CI: 0.752-0.901). Conclusion: NE has a certain inhibitory effect on cellular immune function in patients with septic shock. A prognostic risk model was constructed with stronger prediction efficiency for the prognosis of patients with septic shock.

Delivery of a Hepatitis C Virus Vaccine Encoding NS3 Linked to the MHC Class II Chaperone Protein Invariant Chain Using Bacterial Ghosts.

Efficient delivery of a DNA plasmid into antigen-presenting cells (APCs) is a potential strategy to enhance the immune responses of DNA vaccines. The bacterial ghost (BG) is a potent DNA vaccine delivery system that targets APCs. In the present work, we describe a new strategy of using E. coli BGs as carriers for an Ii-linked Hepatitis C Virus (HCV) NS3 DNA vaccine that improved both the transgene expression level and the antigen-presentation level in APCs. BGs were prepared from DH5α cells, characterized via electron microscopy and loaded with the DNA vaccine. The high transfection efficiency mediated using BGs was first evaluated in vitro, and then, the immune protective effect of the BG-Ii-NS3 vaccine was determined in vivo. It was found that the antibody titer in the sera of BG-Ii-NS3-challenged mice was higher than that of Ii-NS3-treated mice, indicating that the BGs enhanced the humoral immune activity of Ii-NS3. The cellular immune protective effect of the BG-Ii-NS3 vaccine was determined using long-term HCV NS3 expression in a mouse model in which luciferase was used as a reporter for HCV NS3 expression. Our results showed that the luciferase activity in BG-Ii-NS3-treated mice was significantly reduced compared with that in Ii-NS3-treated mice. The CTL assay results demonstrated that BG-Ii-NS3 induced a greater NS3-specific T-cell response than did Ii-NS3. In summary, our study demonstrated that BGs enhanced both the humoral and cellular immune response to the Ii-NS3 DNA vaccine and improved its immune protection against HCV infection.

Investigation on the immune effect of a chitosan-based particle-in-oil-in-water emulsion

Particle-in-oil-in-water (P/O/W) multiple emulsion adjuvants introduce particles into the internal water phase of a water-in-oil-in-water emulsion, combining the advantages of both particle and emulsion adjuvants to enhance humoral and cellular immune responses. In this study, we optimized P/O/W multiple emulsion adjuvants. Chitosan, poly (lactic-co-glycolic acid), and aluminum gel were used to prepare the particles, which were introduced into a water-in-oil-in-water emulsion to obtain three P/O/W multiple emulsion adjuvants. The immune enhancement effects and safety of the three adjuvants were compared, and it was proven that the adjuvant with chitosan nanoparticles in the internal water phase had good cellular and humoral immune effects. Simultaneously, the proportion of the internal water phase increased from 13% to 20%, reducing the antigen concentration required for embedding to one-third of the original concentration and expanding the application range of the composite adjuvant.

Mature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy.

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

Stability analysis of HCV dynamic model with saturation incidence, cellular immunity and interferon effect in intrahepatic and extrahepatic tissues

An HCV model with saturation incidence and cellular immunity is constructed and analyzed. The model takes account of both intrahepatic and extrahepatic tissues and the effect of antiviral drugs especially the interferon. The basic reproduction number R01 and CTL immune reproduction number R02 are calculated, respectively. The existence of three equilibria, namely infection-free, immune response-free, infection-immune coexistence equilibrium is analyzed with a novel method. Stability analysis is also given with corresponding reproduction number, and the results show that when R01<1, there are no virus and immune response existed in the end; when R02<1<R01, the virus survives, but immune response gradually disappears; when R02>1, the system will be globally stable with both virus and immune response existing. Numerical analysis is also given which is consistent with the theoretical analysis.

MRNA-1273 SARS-CoV-2 vaccine in recently transplanted allogeneic hematopoietic cell transplant recipients: Dynamics of cellular and humoral immune responses and booster effect

Allogeneic hematopoietic stem cell transplant (HCT) recipients are at high risk of severe COVID-19 despite vaccination. Little is known about cellular response to SARS-CoV-2 vaccine in this population, especially in recently transplanted patients (RTP). In this single-center study we examined cellular and humoral response to the mRNA-1273 (Spikevax®) vaccine in recently transplanted patients (RTP, n = 49), and compared them to long-term transplanted patients (LTTP, n = 19) and healthy controls (n = 20) at three different timepoints: one and three months after the second dose (T1 and T2, respectively, 28 days apart), and one month after the third dose (T3). Controls did not receive a third dose. RTPs showed lower IgG anti-S1 titers than healthy controls at both T1 (mean 0.50 vs 0.94 arbitrary units -AU-, p < 0.0001) and T2 (0.37 vs 0.79 AU, p < 0.0001). They also presented lower titers than LTTPs at T1 (0.50 vs 0.66, p = 0.01), but no differences at T2 (0.37 vs 0.40 AU, p = 0.55). The rate of positive T-cell responses was lower in RTPs than in controls at both T1 and T2 (61.2 % vs 95 %, p = 0.007; 59.2 % vs 100 %, p = 0.001, respectively), but without statistically significant differences between transplanted groups. At T3 no differences were seen between RTPs and LTTPs as well, neither in IgG antibodies (p = 0.82) nor in cellular responses (p = 0.15), although a third dose increased the rate of positive cellular and humoral responses in approximately 50 % of recently transplanted patients. However, active immunosuppressive treatment severely diminished their chances to produce an adequate response.

Preclinical Assessment of Immunogenicity and Protectivity of Novel ROR1 Fusion Proteins in a Mouse Tumor Model.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a new tumor associated antigen (TAA) which is overexpressed in several hematopoietic and solid malignancies. The present study aimed to produce and evaluate different fusion proteins of mouse ROR1 (mROR1) to enhance immunogenicity and protective efficacy of ROR1. Four ROR1 fusion proteins composed of extracellular region of mROR1, immunogenic fragments of TT as well as Fc region of mouse IgG2a were produced and employed to immunize Balb/C mice. Humoral and cellular immune responses and anti-tumor effects of these fusion proteins were evaluated using two different syngeneic murine ROR1+ tumor models. ROR1-specific antibodies were induced in all groups of mice. The levels of IFN-γ, IL-17 and IL-22 cytokines in culture supernatants of stimulated splenocytes were increased in all groups of immunized mice, particularly mice immunized with TT-mROR1-Fc fusion proteins. The frequency of ROR1-specific CTLs was higher in mice immunized with TT-mROR1-Fc fusion proteins. Finally, results of tumor challenge in immunized mice showed that immunization with TT-mROR1-Fc fusion proteins completely inhibited ROR1+ tumor cells growth in two different syngeneic tumor models until day 120 post tumor challenge. Our preclinical findings, for the first time, showed that our fusion proteins could be considered as a potential candidate vaccine for active immunotherapy of ROR1-expressing malignancies.

English

Historically Artemisia herba alba (AHA) is widely used in traditional Moroccan medicine. Few studies have been carried out to confirm its traditional use, in particularly immunological studies and to the authors&rsquo; knowledge; no study has treated the in vivo immunomodulatory effect of AHA aqueous extracts. This work was established to assess the immunological effects of AHA, including the humoral and cellular immunity effects in vivo. The immunomodulatory effect was assessed by measuring the titer of specific antibodies by the agglutination technique after immunization of Wistar rats with sheep red blood cells, while the pro-inflammatory effect was performed using a carrageenan-induced rat paw edema model. Administered AHA&rsquo;s aqueous extract (AE) appears to have significantly (p &lt; 0.01) stimulated the production of anti-SRBC antibodies with a dose-dependent effect compared to the control. These results were confirmed by a significant increase in the levels of white blood cells in particular neutrophils, lymphocytes, monocytes and eosinophils (p&lt;0.05) for the doses 0.5 and 1 g/ml/bw. For the same doses of the extract, a proinflammatory effect was observed by the size of edema and the presence of very dense inflammatory infiltrate made up of lymphocytes, plasma cells and polymorphonuclear neutrophils. The AHA&rsquo;s AE have shown an important immunomodulatory and pro-inflammatory activities in vivo by enhancing the production of antibodies and the inflammatory reaction. Key words: Artemisia herba alba, Immunomodulatory effect, In vivo, pro-inflammatory effect, antibodies production, aqueous extract.

Preparation and immungenicity of recombinant protein containing intramolecular adjuvant in SARS-CoV-2 RBD domain

A fusion protein containing a tetanus toxin peptide, a tuftsin peptide and a SARS-CoV-2S protein receptor-binding domain (RBD) was prepared to investigate the effect of intramolecular adjuvant on humoral and cellular immunity of RBD protein. The tetanus toxin peptide, tuftsin peptide and S protein RBD region were connected by a flexible polypeptide, and a recombinant vector was constructed after codon optimization. The recombinant S-TT-tuftsin protein was prepared by prokaryotic expression and purification. BALB/c mice were immunized after mixed with aluminum adjuvant, and the humoral and cellular immune effects were evaluated. The recombinant S-TT-tuftsin protein was expressed as an inclusion body, and was purified by ion exchange chromatography and renaturated by gradient dialysis. The renaturated protein was identified by Dot blotting and reacted with serum of descendants immunized with SARS-CoV-2 subunit vaccine. The results showed that the antibody level reached a plateau after 35 days of immunization, and the serum antibody ELISA titer of mice immunized with recombinant protein containing intramolecular adjuvant was up to 1:66 240, which was significantly higher than that of mice immunized with S-RBD protein (P < 0.05). At the same time, the recombinant protein containing intramolecular adjuvant stimulated mice to produce a stronger lymphocyte proliferation ability. The stimulation index was 4.71±0.15, which was significantly different from that of the S-RBD protein (1.83±0.09) (P < 0.000 1). Intramolecular adjuvant tetanus toxin peptide and tuftsin peptide significantly enhanced the humoral and cellular immune effect of the SARS-CoV-2 S protein RBD domain, which provideda theoretical basis for the development of subunit vaccines for SARS-CoV-2 and other viruses.

A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19.

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified in Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing a safe and efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts to produce efficient vaccines inexhaustibly are ongoing. At present time, according to the COVID-19 vaccine tracker and landscape provided by World Health Organization (WHO), there are 161 vaccine candidates in different clinical phases all over the world. In between, protein subunit vaccines are types of vaccines that contain a viral protein like spike protein or its segment as the antigen assumed to elicit humoral and cellular immunity and good protective effects. Previously, this technology of vaccine manufacturing was used in a recombinant influenza vaccine (RIV4). In the present work, we review protein subunit vaccines passing their phase 3 and 4 clinical trials, population participated in these trials, vaccines manufactures, vaccines efficiency and their side effects, and other features of these vaccines.

Heterologous Prime-Boost Immunization with DNA Vaccine and Modified Recombinant Proteins Enhances Immune Response against Trueperella pyogenes in Mice.

Trueperella pyogenes (T. pyogenes) is a crucial opportunistic pathogen normally causing mastitis, abscesses and pneumonia in economically important ruminants. Although only one commercial vaccine of T. pyogenes is currently obtainable, its immunoprotective effect is limited. Pyolysin (PLO) is the most predominant virulence factor highly expressed in T. pyogenes and is an excellent target for the development of novel vaccines against T. pyogenes. In this study, we designed a heterologous prime-boost vaccination scheme combining a DNA vaccine pVAX1-PLO and a subunit vaccine His-PLO to maximize host responses in mice. Humoral and cellular immune responses and protective effects were evaluated in mice to compare the immunogenicity induced by different immunization schemes. Compared to the PBS-control group, in vivo immunization results showed that better immune responses of mice immunized with the pVAX1-PLO plasmids and His-PLO proteins were induced. The residual bacterial burdens from the liver and peritoneal fluid were remarkably decreased in the immunized mice compared with the PBS group. Notably, the heterologous prime-boost vaccination groups significantly enhanced host humoral and cellular immune responses and protected mice from different virulent T. pyogenes strains infection. Conclusively, this study provides a favorable strategy for the further development of next-generation vaccines against T. pyogenes infections.

A New Nano Adjuvant of PF3 Used for an Enhanced Hepatitis B Vaccine.

Recombinant protein vaccines, with highly pure ingredients and good safety, are gradually replacing some attenuated and inactivated vaccines in clinical practice. However, since their low immunogenicity of the recombinant proteins, adjuvants are often needed to enhance immune response after vaccination. Aluminum adjuvant has been widely used in some vaccines for decades, it can induce strong humoral immunity, but the deficiency of cellular immunity limits its application for some vaccines. Therefore, it is urgently needed to develop novel adjuvant to increase not only humoral but also cellular immune response. To address this, we designed and prepared a new nano adjuvant (PF3) through microfluidization by the combination of saponin (Ginsenoside Rg1) and oil-in-water nano emulsion (NE) in the present study. As compared to aluminum adjuvant, PF3 had stronger humoral and cellular immune induction effect because of high cellular uptake and activization of immune response pathways. Furthermore, PF3 showed better immune enhancement and acceptable biosafety equivalent to that of aluminum adjuvant. In addition, no obvious changes of PF3 were observed in size and zeta potential after 12 weeks storage at 4 and 37°C, demonstrating its high stability in vitro. This study provided an adjuvant platform to replace traditional aluminum adjuvant in design of recombinant vaccines.

Heightened levels of circulating cell-free DNA predict aggressive onset of experimental glioblastoma

Abstract Glioblastoma (GBM) is an incurable and aggressive form of brain cancer that is associated with severe peripheral immunosuppression. This immunosuppression is a critical barrier to patient survival and the success of immune modulatory therapies. Using the murine GL261 model of GBM, we recapitulated major features of peripheral immunosuppression observed in patients including spleen atrophy, T cell lymphopenia, and T cell sequestration within the bone marrow. We determined that peripheral immunosuppression in GBM is multifaceted and involves release of novel circulating soluble factors that are found in the serum of glioma-bearing mice. This high molecular weight species potently inhibits T cell proliferation in vitro. Cell-free extracellular DNA has been recently identified as an immune suppressive factor in circulation. We, therefore, assessed cell-free DNA levels in the GL261 model. We determined that serum isolated from glioma-bearing mice harbor significantly higher concentrations of double stranded and single stranded cell-free DNA compared to healthy controls. Serial assessment of DNA concentrations in serum of glioma-bearing mice indicated that the most prominent increase was concurrent with end-stage disease. These findings provide a tractable approach to investigate the cellular source and immune suppressive effects of cell-free DNA in the leading murine model of GBM. Supported by K99NS117799

Raltegravir Inclusion Decreases CD4 T-Cells Intra-Cellular Viral Load and Increases CD4 and CD28 Positive T-Cells in Selected HIV Patients.

Raltegravir (RLT) prevents the integration of HIV DNA in the nucleus, but published studies remain controversial, suggesting that it does not decrease proviral DNA. However, there are only a few studies focused on virus-targeted cells. We aimed our study on the impact of RLT inclusion on total intra-cellular viral DNA (TID) in cellular subsets and immune effects in patients with newly acquired undetectable plasmatic viral load (UVL). Six patients having UVL using an antiretroviral combination for 6 months and CD4 T-cells > 350/mL and <500/mL were selected to receive RLT for 3 months from M0 to M3. Patients had 7 sequential viro-immunological determinations from M-1 to M5. Immune phenotypes were determined by flow cytometry and TID quantification was performed using PCR assay on purified cells. TID (median values) at the initiation of RLT in CD4 T-cells was 117 copies/millions of cells, decreased to 27.5 on M3, and remained thereafter permanently under the cut-off (<10 copies/millions of cells) in 4 out of 6 patients. This was associated with an increase of CD4 and CD4 + CD28+ T-cells and a decrease of HLA-DR expression and apoptosis of CD4 T-cells. RLT inclusion led to decreases in the viral load along with positive immune reconstitution, mainly for CD4 T-cells in HIV patients.

Equivalent humoral and cellular immune response but different side effect rates following SARS-CoV-2 vaccination in peritoneal and haemodialysis patients using messenger RNA vaccines.

Equivalent humoral and cellular immune response but different side effect rates following SARS-CoV-2 vaccination in peritoneal and haemodialysis patients using messenger RNA vaccines.

Assessments of different inactivating reagents in formulating transmissible gastroenteritis virus vaccine

BackgroundTransmissible gastroenteritis virus (TGEV) causes enteric infection in piglets, characterized by vomiting, severe diarrhea and dehydration, and the mortality in suckling piglets is often high up to 100%. Vaccination is an effective measure to control the disease caused by TGEV.MethodsIn this study, cell-cultured TGEV HN-2012 strain was inactivated by formaldehyde (FA), β-propiolactone (BPL) or binaryethylenimine (BEI), respectively. Then the inactivated TGEV vaccine was prepared with freund's adjuvant, and the immunization effects were evaluated in mice. The TGEV-specific IgG level was detected by ELISA. The positive rates of CD4+, CD8+, CD4+IFN-γ+, CD4+IL-4+ T lymphocytes were detected by flow cytometry assay. Lymphocyte proliferation assay and gross pathology and histopathology examination were also performed to assess the three different inactivating reagents in formulating TGEV vaccine.ResultsThe results showed that the TGEV-specific IgG level in FA group (n = 17) was earlier and stronger, while the BEI group produced much longer-term IgG level. The lymphocyte proliferation test demonstrated that the BEI group had a stronger ability to induce spleen lymphocyte proliferation. The positive rates of CD4+ and CD8+ T lymphocyte subsets of peripheral blood lymphocyte in BEI group was higher than that in FA group and BPL groups by flow cytometry assay. The positive rate of CD4+IFN-γ+ T lymphocyte subset was the highest in the BPL group, and the positive rate of CD4+IL-4+ T lymphocyte subset was the highest in the FA group. There were no obvious pathological changes in the vaccinated mice and the control group after the macroscopic and histopathological examination.ConclusionsThese results indicated that all the three experimental groups could induce cellular and humoral immunity, and the FA group had the best humoral immunity effect, while the BEI group showed its excellent cellular immunity effect.

The efficacy and mechanism of CD020 on the induction of specific immune responses against HPV-related cancer

Abstract Virus infections may account for the development of several cancers, such as HPV16/18 are known to cause around 70% of cervical cancer cases. Until now, several immunotherapeutic approaches for virus-induced cancer are under development. Peptide-based vaccines have several advantages over conventional whole-protein vaccines in terms of purity, lot-to-lot consistency, production costs, and high antigenic specificity. However, the use of peptide antigens in vaccine development has been hampered by problems, such as weak immunogenicity coupled with a paucity of potent adjuvants. Specific T cell immune response is crucial for anti-tumor immunity. CD020 is a compound derived from the Chinese herbal medicine (CHM) of Hedyotis diffusa Willd. However, the efficacy and mechanism of CD020 on the induction of specific immune responses against cancer are still unclear. Therefore, we aimed to investigate whether CD020 can modulate specific T cell responses to apply for the development of a cancer vaccine. We have identified that CD020 could increase expression of maturation cytokines and activation markers of BM-DCs and induce specific T cell responses. Furthermore, in a murine TC-1 tumor-bearing model, we found that the CD020 could act as an adjuvant to induce cellular immune responses and anti-tumor effect in the peptide vaccine strategy. We suggested that immune-stimulator CD020 combined with cancer vaccine endows them with increased immunologic activity, which may be used to bypass the requirement for the conditional adjuvant. Further delineation of the mechanism may provide new clues for vaccination strategy.

Physiological, histopathological and cellular immune effects of Pergularia tomentosa extract on Locusta migratoria nymphs

The migratory locust Locusta migratoria (Orthoptera, Acrididae) is one of the most important pests due to its extensive and severe damage to crops in large parts of Africa and Asia. Biodegradable and ecologically natural products such as botanical insecticides are emerging candidates for replacement of usually applied chemical pesticides. The crude methanolic extract of Pergularia tomentosa (PME) was investigated for their toxicity and physiological aspects on L. migratoria nymphs. Results showed that treatment of newly emerged fourth and fifth instar nymphs resulted in significant mortality and significant repellent activity with an LC50 value of 0.18 and 0.38%, respectively, after seven days of treatment. The PME toxicity was also demonstrated by histopathological changes in the alimentary canal resulting in considerable disorganization and severe damage of the caeca and proventriculus structure. The extract induced cellular immune reactions which manifested by a significant decrease in the number of the differential haemocyte counts (prohemocytes and plasmatocytes) and important cell lysis. Data of biochemical analyses showed that the PME reduced the activity of acetylcholinesterase and induced the glutathione S-transferases. The neurotoxic effect was confirmed by the histological alterations in the brain structure, particularly in the neurosecretory cells showing typical signs of cell necrosis.