Avaliação do perfil de citocinas séricas e óxido nítrico na hanseníase experimental murina / Evaluation of the serum cytokines profile and nitric oxide in experimental murine leprosy

Introdução: a hanseníase é uma do-ença infecciosa crônica causada pelo Mycobacterium leprae (M. leprae), um para-sita intracelular obrigatório. Assim, a resis-tência do hospedeiro a esse patógeno depen-de da imunidade celular. O uso de modelos experimentais tem permitido o estudo da hanseníase do ponto de vista imunológico, microbiológico e terapêutico, entretanto, as diferenças na progressão da infecção entre os modelos mais empregados (camundongos imunocompetentes, BALB/c, e camundongos congenitamente atímicos, nude) são pouco estudadas. Objetivo: comparar a evolução da infecção pelo M. leprae em camundongos BALB/c e nude quanto à multi-plicação bacilar e avaliação do perfil inflamatório sistêmico pela quantificação sérica de citocinas e óxido nítrico (NO). Métodos: os camundongos foram inoculados com M. leprae nos coxins plantares e avaliados aos 3, 5 e 8 meses após a infecção. Resultados: camundongos nude apresentaram multiplicação bacilar progressiva nos coxins plantares. Em camundongos BALB/c, o número de bacilos foi maior aos 5 meses. Em relação à quantificação de citocinas, nos camundongos BALB/c houve aumento de IL-2 e IL-17A e diminuição de IL-6 e NO aos 8 meses de inoculação. Nos camundongos nude, verificou-se o aumento do TNF aos 8 meses de inoculação e manutenção dos níveis de NO. Conclusão: os resultados encontrados sugerem que em camundongos BALB/c ocorre a ativação de uma resposta imune capaz de controlar a multiplicação do M. leprae, em contrapartida em camundongos nude a infecção é progressiva a despeito de altos níveis de TNF. (AU)

Introduction: leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an obligate intracellular parasite. Thus, host resistance to this pathogen depends on cellular immunity. The use of experimental models has made it possible to study leprosy from an immunological, microbiological, and therapeutic point of view. However, the differences in the progression of the infection between the most used models (immunocompetent mice, BALB/c, and congenitally athymic mice, nude) have been little studied. Objective: to compare the evolution of M. leprae infection in BALB/c and nude mice in terms of bacillary multiplication and evaluation of the systemic inflammatory profile by quantifying serum cytokines and nitric oxide (NO). Methods: the mice were inoculated with M. leprae in the footpads and evaluated at 3, 5, and 8 months after infection. Results: nude mice showed progressive bacillary multiplication in the footpads. In BALB/c mice, the number of bacilli was higher at 5 months. In terms of cytokine quantification, BALB/c mice showed an increase in IL-2 and IL-17A and a decrease in IL-6 and NO at 8 months of inoculation. In the nude mice, there was an increase in TNF at 8 months of inoculation and maintenance of NO levels. Conclusion: the results suggest that BALB/c mice activate an immune response capable of controlling the multiplication of M. leprae, whereas in nude mice the infection is progressive despite high levels of TNF. (AU)

Advances in methodologies for evaluating cell-mediated immune responses / 生物工程学报

Cell-mediated immune response is an important part of machinery in maintaining the body's homeostasis. After the innate immune system selectively activates the adaptive immune system, the cell-mediated immunity exerts its killing and clearance functions. Therefore, evaluating the level of cell-mediated immune response is crucial in the diagnosis and treatment of cancer, monitoring the immune status after organ transplantation, diagnosing and preventing viral diseases, and evaluating the effectiveness of vaccines and other areas. From the initial overall assessment of the immune effects in vivo to the precise detection of the number and function of multiple immune cells, the evaluation methods of cell-mediated immune response have greatly advanced. However, cell-mediated immune response involves multiple levels in the body, and it's difficult to choose the numerous detection methods available. The article systematically compares the evaluation methods of cell-mediated immune response at four different levels: the organism, the tissue and organ, the immune cells and the immune molecules, with the aim to facilitate the applications of related technologies.

Characterization of the cellular immune response induced by Mycobacterium tuberculosis Rv2626c / 生物工程学报

Nearly a quarter of the world's population is infected with Mycobacterium tuberculosis and remains long-term asymptomatic infection. Rv2626c is a latent infection-related protein regulated by DosR of M. tuberculosis. In this study, the Rv2626c protein was prokaryotically expressed and purified, and its immunobiological characteristics were analyzed using RAW264.7 cells and mice as infection models. SDS-PAGE and Western blotting analysis showed that the Rv2626c-His fusion protein was mainly expressed in soluble form and specifically reacted with the rabbit anti-H37RV polyclonal serum. In addition, we found that the Rv2626c protein bound to the surface of RAW264.7 macrophages and up-regulated the production of NO. Moreover, the Rv2626c protein significantly induced the production of pro-inflammatory cytokines IFN-γ, TNF-α, IL-6 and MCP-1, and induced strong Th1-tendency immune response. These results may help to reveal the pathogenic mechanism of M. tuberculosis and facilitate the development of new tuberculosis vaccine.

Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Disseminaded coccidiodomycosis presentig as acute respiratory distress syndrome in a liver postrasplant recipient / Síndrome de dificultad respiratoria aguda (SDRA) como prensentacion de Coccidiodomicosis diseminada en un paciente receptor de trasplante hepatico ortotópico

Abstract Acute respiratory distress syndrome (ARDS) is a respiratory process of acute onset, showing on X rays as bilateral pulmonary infiltrates and severe respiratory failure, Coccidiodomycosis is a unusual cause of acute respiratory distress syndrome, the incidence of coccidiomycosis in a solid organ trasplant recipientes ranges from 1.4% a 6.9%, inadecuancy of cellular inmunity is a well established risk factor for development of coccididomcosis, less than 1% of patients develop disseminaded infecction and carrying high mortality, the case that we are presenting add to the small list of reports documenting the ocasionally acute and agressive nature of the disseminated clinical form of coccidiodomycosis.

Resumen El síndrome de dificultad respiratoria aguda (SDRA) es un proceso respiratorio de inicio agudo, que se manifiesta en las radiografías como infiltrados pulmonares bilaterales, clinicamente como insuficiencia respiratoria grave, la coccidiodomicosis es una causa inusual de síndrome de dificultad respiratoria aguda, la incidencia de coccidiomicosis en receptores de trasplante de órgano sólido varía desde 1.4% a 6.9%, una inadecuada inmunidad celular es un factor de riesgo bien establecido para el desarrollo de coccidomicosis, menos del 1% de los pacientes desarrollan enfermedad diseminada y alta mortalidad, el caso que presentamos se suma a la pequeña lista de informes que documentan la naturaleza ocasionalmente aguda y agresiva de la forma clínica diseminada de coccidiodomicosis.

Experimental studies using OMV in a new platform of SARS-CoV-2 vaccines

Although COVID-19 vaccines have recently been approved for emergency use, search for new vaccines are still urgent, since the access of the countries, especially the poorest, to the vaccines, has shown to be slower than the necessary to rapidly control the pandemic. We proposed a novel platform for vaccine using recombinant receptor binding domain (rRBD) from Sars-Cov-2 spike protein and Neisseria meningitidis outer membrane vesicles (OMVs). The antigen preparation produced a humoral and cellular immune response. Taken together our findings suggest a good immunostimulatory patter in response to immunization with rRBD plus N. meningitidis OMV.

Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord / 亚洲男科学杂志(英文版)

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

ISA 61 VG adjuvant enhances protective immune response of Listeria monocytogenes inactivated vaccine / 生物工程学报

Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.

Preparation and characterization of HBc virus like particles with site-directed coupling function / 生物工程学报

Hepatitis B virus core protein can self-assemble into icosahedral symmetrical viral-like particles (VLPs) in vitro, and display exogenous sequences repeatedly and densely on the surface. VLPs also have strong immunogenicity and biological activity. When the nanoparticles enter the body, they quickly induce specific humoral and cellular immune responses to exogenous antigens. In this study, we designed an HBc-VLPs that can be coupled with antigens at specific sites, and developed a set of efficient methods to prepare HBc-VLPs. Through site-specific mutation technology, the 80th amino acid of peptide was changed from Ala to Cys, a specific cross-linking site was inserted into the main immunodominant region of HBc-VLPs, and the prokaryotic expression vector pET28a(+)-hbc was constructed. After expression and purification, high purity HBc(A80C) monomer protein was assembled into HBc-VLPs nanoparticles in Phosphate Buffer. The results of particle size analysis show that the average particle size of nanoparticles was 29.8 nm. Transmission electron microscopy (TEM) showed that HBc-VLPs formed spherical particles with a particle size of about 30 nm, and its morphology was similar to that of natural HBV particles. The influenza virus antigen M2e peptide as model antigen was connected to Cys residue of HBc-VLPs by Sulfo-SMCC, an amino sulfhydryl bifunctional cross-linking agent, and M2e-HBc-VLPs model vaccine was prepared. The integrity of HBc-VLPs structure and the correct cross-linking of M2e were verified by cell fluorescence tracing. Animal immune experiments showed that the vaccine can effectively stimulate the production of antigen-specific IgG antibody in mice, which verified the effectiveness of the vaccine carrier HBc-VLPs. This study lays a foundation for the research of HBc-VLPs as vaccine vector, and help to promote the development of HBc-VLPs vaccine and the application of HBc-VLPs in other fields.

Las células dendríticas plasmacitoides evocan la respuesta efectora de los linfocitos T citotóxicos específicos para Salmonella / The plasmacytoid dendritic cells evoke Salmonella-specific CTL effector response

Resumen Introducción. La función inmunológica de las células dendríticas plasmacitoides durante las infecciones bacterianas, como la de Salmonella spp., es poco conocida. En ese contexto, se analizó su función efectora para presentar antígenos de Salmonella Typhimurium ante linfocitos T citotóxicos. Objetivo. Analizar la respuesta de los linfocitos T citotóxicos específicos para Salmonella evocada por las células dendríticas plasmacitoides. Materiales y métodos. Se usaron células dendríticas plasmacitoides marcadas con éster de succinimidil-carboxifluoresceína, pulsadas con el epítopo de Salmonella OmpC73 Kb- restringido o infectadas con S. Typhimurium como blanco en ensayos de citotoxicidad. Resultados. La lisis específica tuvo significación estadística usando células dendríticas plasmacitoides positivas pulsadas con OmpC73 en todas las relaciones de células efectoras y blanco (E:B) (p≤0,05); en cuanto a las células dendríticas plasmacitoides positivas para S. Typhimurium, solo se observó significación estadística en la relación de 1:100 (p≤0,05) usando las células efectoras OmpC73. Conclusión. Las células dendríticas plasmacitoides pueden evocar la respuesta de los linfocitos T citotóxicos durante la infección con S. Typhimurium.

Abstract Introduction: The immunological role of plasmacytoid dendritic cells (pDC) in bacterial infections such as Salmonella has been poorly documented. Therefore, we analyzed the effector function of these cells by presenting cytotoxic T lymphocytes (CTL) with Salmonella Typhimurium antigens. Objective: To analyze the Salmonella-specific CTL response evoked by pDCs. Materials and methods: We used plasmacytoid dendritic cells stained with carboxyfluorescein succinimidyl ester (CFSE) and pulsed with OmpC73, Salmonella Kb- restricted epitopes or S. Typhimurium as targets for cytotoxicity assays. Results: Specific lysis was shown to be statistically significant in pDC + OmpC73 for all effector:target ratios (p≤0.05). For pDC + S. Typhimurium, statistical significance was only observed at a 1:100 ratio (p≤0.05) using OmpC73. Conclusion: Plasmacytoid dendritic cells evoke CTL response during S. Typhimurium infection.

Mecanismos efetores da resposta imune na infecção por Bordetella pertussis / Immune response effector mechanisms to Bordetella pertussis infection

A coqueluche é uma doença infecciosa aguda, transmissível, com predileção pelo trato respiratório, caracterizada por paroxismos de tosse seca e considerada uma importante causa de morbidade e mortalidade infantil. A resposta imunológica humoral e celular do hospedeiro promove a contenção da infecção, pois essas respostas se caracterizam como importantes linhas de defesa durante a infecção e colonização da bactéria. Dessa forma, esta revisão bibliográfica procurou descrever os mecanismos mais eficazes de resposta imune contra Bordetella pertussis e abordar os mecanismos de evasão utilizados pelo patógeno.

Pertussis is a transmissible infectious disease with a predilection for the respiratory tract characterized by paroxysms of dry cough. It is considered an important cause of child morbidity and mortality. The humoral and cellular immune responses of the host promote the containment of the infection, and these responses are characterized as important lines of defense during infection and colonization of the bacterium. Thus, this literature review sought to describe the most effective immune response mechanisms against Bordetella pertussis and to address the avoidance mechanisms used by the pathogen.

Subsets of T lymphocytes in the lesional skin of pityriasis rosea

Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.

Β-Glucan of candida albicans cell wall extract inhibits salmonella typhimurium colonization by potentiating cellular immunity (cd8 + and cd4 + t cells)

Abstract INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.

Expression of CD44, CD87 and CD123 in Acute Leukemia and Its Correlation with Cellular Immunity / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of CD44, CD87 and CD123 in acute leukemia and its correlation with cellular immune markers.@*METHODS@#A total of 166 patients with acute leukemia (AL) admitted from May 2014 to February 2017 were enrolled in AL groups. Among these patients, 100 patients suffered from acute myeloid leukemia, 50 patients suffered from acute lymphoid leukemia, and 16 patients showed B/medullary phenotype. At the same time 50 patients with non-acute leukemia were enrolled in the control group. 5 ml of fasting venous blood collected from the patients in each group, and the percentage of CD44, CD87 and CD123 cells was determined by three-color flow cytometry. Symptomatic chemotherapy was given to the patients with confirmed acute leukemia, and the remission was evaluated after 2 treatmen courses. The Complete remission (CR) was recorded and the percentage of CD44, CD87 and CD123 cells under different curative efficacy were recorded. The correlation of the prognosis patients with CD44, CD87 and CD123 was analyzed by SPSS Pearson correlation analysis software.@*RESULTS@#The positive rates of CD44, CD87 and CD123 in AL group were all higher than those in the control group (P＜0. 05). The positive rates of CD44 and CD123 in acute myeloid leukemia group were higher than those in acute lymphoblastic leukemia group and B/myeloid phenotype group (P＜0. 05). The positive rate of CD44 in acute lymphoid leukemia group was higher than that in B/medullary double phenotype group (P＜0.05). The treatment in the patients of AL group was successfully completed. 132 patients reachel to CR and 34 patients to PR+NR after 2 courses. The positive rates of CD44, CD87 and CD123 in CR patients were lower than those in PR+NR patients (P＜0.05). The results of SPSS Pearson correlation analysis showed that the prognosis of patients with acute leukemia negatively correlated with CD44 and CD87 (P＜0.05).@*CONCLUSION@#The expression of CD44, CD87 and CD123 in different phenotype of acute leukemia are different, which correlateds with prognosis. The determination of CD44, CD87 and CD123 can be used to evaluate the prognosis of patients for the reference of clinical treatment.

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years / 소아과

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.

Correlation between galectin-3 level in bronchoalveolar lavage fluid and cellular immunity in children with refractory Mycoplasma pneumoniae pneumonia / 中国当代儿科杂志

OBJECTIVE@#To study the correlation of galectin-3 level in bronchoalveolar lavage fluid (BALF) with Mycoplasma pneumoniae (MP) load and cellular immunity of neutrophils and macrophages in the airway in children with refractory MP pneumonia (RMPP).@*METHODS@#A total of 64 children with RMPP who were hospitalized from January 2013 to January 2017 were enrolled. In addition to the conservative medical treatment, all the 64 children with RMPP were given bronchoalveolar lavage in the acute stage (5-7 days after admission) and 48 out of the 64 children were given bronchoalveolar lavage in the recovery stage (10-14 days after admission). Four milliliters of BALF of the affected lung lobe or segment were collected. ELISA was used to measure the level of galectin-3 in BALF supernatant. RT-PCR was used to measure MP load. Hematoxylin and eosin staining was used to measure the percentage of neutrophils and macrophages. Six children with bronchial foreign bodies were enrolled as the control group.@*RESULTS@#The RMPP group had a significantly higher level of galectin-3 in BALF in both the acute and recovery stages than the control group (P0.05). The RMPP group had a significantly higher MP load in BALF in both the acute and recovery stages than the control group (P<0.01), and the MP load in the acute stage was significantly higher than in the recovery stage (P<0.01). In the children with RMPP, galectin-3 level in BALF in the acute stage was positively correlated with MP load and the percentage of neutrophils (r=0.789 and 0.726 respectively; P<0.01).@*CONCLUSIONS@#Galectin-3 is involved in the process of airway inflammation in children with RMPP, and the level of galectin-3 in BALF is positively correlated with MP load. RMPP is a cellular immune inflammatory lesion with the increase of neutrophils and the reduction in macrophages. Galectin-3 is closely associated with neutrophil chemotaxis and luminal infiltration in children with RMPP. MP load gradually decreases with the recovery from RMPP, but it is not completely eliminated by the immune system in the recovery stage. MP infection can increase the consumption of macrophages in children with RMPP.

Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus

PURPOSE: Respiratory syncytial virus (RSV) can cause serious respiratory illnesses such as pneumonia, asthma, and bronchiolitis in infants and elderly or immunocompromised individuals. An RSV vaccine has yet to be developed; only prophylactic anti-RSV antibody is commercially available. So, we investigated whether our vaccine candidate is able to induce type 1 CD4+ T helper (Th1), CD8+ T-cell responses, and protective immunity without vaccine-enhanced disease (VED) against RSV. MATERIALS AND METHODS: We used RSV G protein fragment (Gcf A) with recombinant baculovirus capable of expressing the RSV M2 protein (Bac M2) as a vaccine candidate, and injected this vaccine (Gcf A/Bac M2) intramuscularly, and challenged with RSV intranasally into mice. Enzyme-linked immunosorbent assay, flow cytometry, plaque assay, and weight measurement were performed to confirm humoral immunity, cellular immunity, and protective immunity. RESULTS: The Gcf A/Bac M2 formulation induced a stronger IgG response to Gcf A than Gcf A inoculation alone, and the ratio of IgG1/IgG2a indicated that the responses shifted predominantly to Th1. In addition, both RSV G-specific Th1 responses and RSV M2-specific CD8+ T-cell responses were induced, and G protein-associated eosinophilic infiltration was suppressed compared to the control group. Moreover, the Gcf A/Bac M2 group showed effective protection after an RSV challenge. CONCLUSION: Bac M2 could serve as a vaccine with intrinsic adjuvant activity, and the Gcf A/Bac M2 shows promise as a vaccine candidate for inducing protective immunity without inciting VED.

Ethical considerations of cellular immunotherapy for cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.

An attenuated Salmonella vaccine secreting Lawsonia intracellularis immunogenic antigens confers dual protection against porcine proliferative enteropathy and salmonellosis in a murine model

Porcine proliferative enteropathy (PPE) caused by Lawsonia intracellularis (LI) is a global cause for substantial economic losses in the swine industry. Here, we constructed live attenuated Salmonella typhimurium (ST) mutant strains expressing and secreting 4 selected immunogenic LI antigens, namely, optA, optB, Lawsonia flagellin (LfliC), and Lawsonia hemolysin (Lhly); the resultant recombinant strains were designated Sal-optA, Sal-optB, Sal-LfliC, or Sal-Lhly, respectively. Using the BALB/c mouse model, we demonstrate that mice vaccinated once orally, either with a mixture of all 4 recombinant strains or with an individual recombinant strain, show significant (p < 0.05) production of LI-specific systemic immunoglobulin (Ig) G and mucosal IgA responses compared to the Salmonella alone group. Upon restimulation of vaccinated splenocytes with the LI-specific antigens, significant (p < 0.05) and comparable production of interferon-γ responses are found in all vaccinated groups, except the Sal-Lhly group, which shows non-significant levels. Challenge studies were performed in C57BL/6 vaccinated mice. On challenge with the LI (10(6.9) 50% tissue culture infectious dose) 14 days post-vaccination, 20% (1/5) of mice in all vaccinated groups, except Sal-Lhly group, show the presence of the LI-specific genomic DNA (gDNA) in stool samples. In contrast, 40% (2/5) and 60% (3/5) of mice vaccinated with the Sal-Lhly strain and the attenuated Salmonella alone, respectively, were found positive for the LI-specific gDNA. Furthermore, 0% mortality was observed in mice vaccinated against the ST challenge compared to the 30% mortality observed in the unvaccinated control group. In conclusion, we demonstrate that the Salmonella-based LI-vaccines induce LI-specific humoral and cell-mediated immunities, and encompass the potential to offer dual protection against PPE and salmonellosis.