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Th1 And Th2 And Vaccine Effects

Takashi Kimoto, Hyejin Kim, Satoko Sakai, Etsuhisa Takahashi, Hiroshi Kido
We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC II+ CD11c+ cells and their CD11b+ CD103+ and CD11b+ CD103- subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10...
December 13, 2018: Vaccine
Archana Thakur, Ritesh Rathore, Sri Vidya Kondadasula, Joseph P Uberti, Voravit Ratanatharathorn, Lawrence G Lum
This proof-of-concept study investigates the immune effects in metastatic breast cancer (MBC) patients after "vaccination" with activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2 BATs) followed by immune consolidation with immune ATC "boost" after high dose chemotherapy (HDC) and autologous stem cell transplant (SCT). Approximately 2 weeks after completion of vaccination portion of the study, immune T cells were obtained by leukopheresis, activated and expanded ex vivo and re-infused after HDC and SCT to test the hypothesis that transfer of immune unarmed ATC would accelerate reconstitution of anti-tumor activity after SCT...
2018: Oncoimmunology
Inam Ullah Khan, Farooq Ahmad, Shuren Zhang, Panpan Lu, Jingbo Wang, Jun Xie, Naishuo Zhu
The induction of a dominant Th2-type response is the main cause of harmful inflammation in respiratory syncytial virus (RSV) vaccines trials. A balanced Th1 versus Th2 immune response is needed for a safe and effective RSV vaccine. In this study, we evaluated the potential of a recombinant protein SBP-FG as vaccine candidate with main focus on shifting the harmful Th2 response to Th1 response. SBP-FG consists of epitopes from RSV fusion (F) and attachment (G) proteins conjugated to the N-terminal of HBsAg-binding protein (SBP)...
November 20, 2018: International Immunology
Peiyu Li, Ji Wang, Miao Cao, Qiwen Deng, Shibo Jiang, Mei X Wu, Lu Lu
Skin contains a large number of antigen presenting cells, making intradermal (ID) injection one of the most effective ways for vaccine administration. However, although current adjuvants may cause severe local reactions and inflammations in the skin, no adjuvant has been approved for ID vaccination so far. Here, we report that topical application of all- trans retinoic acid (ATRA), a vitamin A derivative produced in the human body, augmented cutaneous influenza vaccination. The adjuvant effects were evaluated in a murine vaccination/challenge model by using A/California/07/2009 pandemic vaccine (09V) or a seasonal influenza vaccine (SIV)...
2018: Frontiers in Microbiology
Sujay Gaikwad, Yogita Pawar, Sharmila Banerjee, Savita Kulkarni
Juglone, a naphthoquinone is a known phytotoxic and cytotoxic allelochemical. Various anticancer studies suggest that pharmacological ROS insult and enzymes inhibited by juglone could be of therapeutic utility. In this study, we show that juglone induces immunomodulation in BCG-vaccinated mice. We have shown that juglone treatment leads to the generation of Th1 cytokines which develops an M1 phenotype in splenic macrophages. These findings were supported by a decrease in Treg population in BCG-vaccinated mice treated with juglone...
November 10, 2018: Toxicon: Official Journal of the International Society on Toxinology
Cheng-Jang Wu, Pin-Hsun Tseng, Cheng-Chi Chan, Sara Quon, Li-Chen Chen, Ming-Ling Kuo
Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a...
2018: Journal of Immunology Research
Li Song, Dan Xiong, Xilong Kang, Yang Jiao, Xiaohui Zhou, Kaiyue Wu, Yi Zhou, Xinan Jiao, Zhiming Pan
H7N9 influenza virus has an unusually high fatality rate of approximately 40%, and a safe and effective vaccine against this subtype is urgently needed. Flagellin, a Toll-like receptor (TLR) 5 agonist, has been deemed as a potent adjuvant candidate. However, its high antigenicity and potential for causing inflammatory injury might restrict its clinical application. Previously, we demonstrated that a fusion protein, HA1-2-FliC, comprising the hemagglutinin globular head protein (HA1-2) of H7N9 influenza virus and the full-length Salmonella typhimurium flagellin protein (FliC), had high efficiency against H7N9 in mouse and chicken models...
October 30, 2018: Antiviral Research
Binbin Ding, Shuai Shao, Chang Yu, Bo Teng, Meifang Wang, Ziyong Cheng, Ka-Leung Wong, Ping'an Ma, Jun Lin
Reported immunoadjuvants still have many limitations, such as inferior cellular uptake capacity and biocompatibility, overly large particle sizes, single function, and unsatisfactory therapeutic efficacy. Here, large-pore mesoporous-silica-coated upconversion nanoparticles (UCMSs) with a size of less than 100 nm are successfully prepared by a typical silica sol-gel reaction using mesitylene as a pore-swelling agent and are applied as a novel immunoadjuvant. The obtained UCMSs not only show significantly higher loadings for the photosensitizers merocyanine 540 (MC540), model proteins (chicken ovalbumin (OVA)), and tumor antigens (tumor cell fragment (TF)), but also are successfully employed for highly efficient in vivo vaccine delivery...
November 2, 2018: Advanced Materials
Munir Mosaheb, Lee M Wetzler
Vaccines formulated with adjuvant have been effective against numerous infectious diseases, almost always due to induction of functional antibodies that recognizes the pathogen of interest. There is an unmet clinical need for vaccine adjuvants that induce T cells responses to potentially enhance protection against malignancies and intracellular pathogens, where a humoral response, alone, may not be adequate for protection. In this study, we demonstrate that a TLR2 ligand-based adjuvant, meningococcal PorB, has broad immunostimulatory activity with the ability to induce a robust and diverse vaccine antigen specific T cell response...
November 29, 2018: Vaccine
Soojin Park, Youri Lee, Young-Man Kwon, Young-Tae Lee, Ki-Hye Kim, Eun-Ju Ko, Jae Hwan Jung, Manki Song, Barney Graham, Mark R Prausnitz, Sang-Moo Kang
Intramuscular (IM) vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) failed in clinical trials due to vaccine-enhanced respiratory disease. To test the efficacy of skin vaccination against respiratory syncytial virus (RSV), we investigated the immunogenicity, efficacy, and inflammatory disease after microneedle (MN) patch delivery of FI-RSV vaccine (FI-RSV MN) to the mouse skin with or without an adjuvant of monophosphoryl lipid A (MPL). Compared to IM vaccination, MN patch delivery of FI-RSV was more effective in clearing lung viral loads and preventing weight loss, and in diminishing inflammation, infiltrating immune cells, and T helper type 2 (Th2) CD4 T cell responses after RSV challenge...
2018: PloS One
Binnian Zhu, Tianyu He, Xiangyun Gao, Minghua Shi, Hongxiang Sun
PURPOSE: The purified fraction of Albizia julibrissin saponins (AJSAF) was evaluated and characterized for the adjuvant activity on porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. METHODS: The effects of AJSAF on serum PRRSV N protein-specific antibody titers, splenocyte proliferation, natural killer (NK) cell activity, mRNA expression of cytokines and transcription factors, secretion of cytokines, T cells response in splenocytes, as well as delayed type hypersensitivity (DTH) in the mice immunized PRRSV vaccine were determined by ELISA, MTT assay, flow cytometry and quantitative real-time PCR (qRT-PCR)...
October 16, 2018: Immunological Investigations
Michael A Collier, Robert D Junkins, Matthew D Gallovic, Brandon M Johnson, Monica M Johnson, Andrew N Macintyre, Gregory D Sempowski, Eric M Bachelder, Jenny P-Y Ting, Kristy M Ainslie
Vaccines are the most effective tool for preventing infectious diseases; however, subunit vaccines, considered the safest type, suffer from poor immunogenicity and require adjuvants to create a strong and sustained immune response. As adjuvants, pathogen-associated molecular patterns (PAMPs) offer potent immunostimulatory properties and defined mechanisms of action through their cognate pattern recognition receptors (PRRs). Their activity can be further enhanced through combining two or more PAMPs, particularly those that activate multiple immune signaling pathways...
November 5, 2018: Molecular Pharmaceutics
Rolf Billeskov, Babak Beikzadeh, Jay A Berzofsky
During the past 3-4 decades, an increasing amount of evidence has pointed to the complex role of the antigen dose or T cell receptor (TCR) stimulation strength on the subsequent type, duration and "flavor" or quality of the response. Antigen dose was initially shown to impact Th1/Th2 bias, and later also shown to differentially affect development and induction of Tregs, Th17, T-follicular helper (Tfh), cells, and others. In recent years the quality of both CD4/8 T cells during infections, cancer and/or autoimmunity has turned out to be critical for subsequent disease outcome...
October 2, 2018: Human Vaccines & Immunotherapeutics
Woo Sik Kim, Jong-Seok Kim, Hong Min Kim, Kee Woong Kwon, Seok-Yong Eum, Sung Jae Shin
Antigens (Ags) in Mycobacterium tuberculosis (Mtb) that are constitutively expressed, overexpressed during growth, essential for survival, and highly conserved may be good vaccine targets if they induce the appropriate anti-Mtb Th1 immune response. In this context, stress response-related antigens of Mtb might serve as attractive targets for vaccine development as they are rapidly expressed and are up-regulated during Mtb infection in vivo. Our group recently demonstrated that GrpE, encoded by rv0351 as a cofactor of heat-shock protein 70 (HSP70) in the DnaK operon, is a novel immune activator that interacts with DCs to generate Th1-biased memory T cells in an antigen-specific manner...
September 26, 2018: Scientific Reports
Gayeon Won, John Hwa Lee
Flagellin, a major structural component of bacteria flagella, is responsible for facilitating motility and invading host cells. The binding capacity of flagellin to toll-like receptor 5 (TLR5) and its trigger action for innate immunity make it an attractive vaccine adjuvant. In this work, we explored the efficacy of F18+ STEC flagellin as an adjuvant in a ghost vaccine candidate against porcine edema disease (ED). TLR5-stimulating activity and IL-8 cytokine expression produced via downstream signaling following ligand exposure was detected in HEK-Blue™-hTLR5 cells stimulated with flagellin expressed in the Salmonella Typhimurium (ST) ghost, JOL1485...
June 2018: Comparative Immunology, Microbiology and Infectious Diseases
Yewande O Fasina, Hyun S Lillehoj
Necrotic enteritis toxin B (NetB)-producing Clostridium perfringens (CP) type A is the etiological agent of necrotic enteritis (NE) - an economically significant disease in broiler chickens. Understanding the immune response to CP infection in broiler chickens is becoming important to develop effective vaccines against NE. An experiment was conducted to determine the expression levels of selected cytokine genes in the intestine and cecal tonsil of CP-challenged broiler chickens. In a floor-pen housing, broiler chickens were randomly assigned to the following treatment groups: 1) bacitracin methylene disalicylate (BMD)-free control diet with no CP challenge (CX), 2) BMD-supplemented diet with no CP challenge (CM), 3) BMD-free control diet with CP challenge (PCX), or 4) BMD-supplemented diet with CP challenge (PCM)...
September 17, 2018: Poultry Science
Robert F Kelly, Rebecca Callaby, Nkongho F Egbe, Diana J L Williams, Ngu Ngwa Victor, Vincent N Tanya, Melissa Sander, Lucy Ndip, Richard Ngandolo, Kenton L Morgan, Ian G Handel, Stella Mazeri, Adrian Muwonge, Barend M de C Bronsvoort
Bovine tuberculosis (bTB), caused by Mycobacterium bovis , remains a major livestock and public health problem in both high and low-income countries. With the current absence of an effective vaccine, control in cattle populations is reliant on regular testing and removal of positive animals. However, surveillance and control are hampered by imperfect diagnostic tests that have poorly described properties in naturally infected populations. Recent research in cattle co-infected with the temperate liver fluke, Fasciola hepatica , has raised concerns about the performance of the intradermal skin test in high fluke incidence areas...
2018: Frontiers in Veterinary Science
Lin Zhang, Dongmei Lin, Haiyan Li, Sen Yu, Junping Bai, Zhiyong Ding, Jiaqiang Wu
Vaccination is an important approach for the control of avian viral diseases. The aim of this study was to evaluate the immune-potentiating effect of oral administration of Inonotus obliquus fermentation products (IOFP) at vaccination in chickens. In total, 120 one-day-old specific-pathogen-free chickens were randomly assigned to six groups: groups 1 to 3 were vaccinated with Newcastle disease virus (NDV) LaSota live vaccine via intranasal and eye-dropped route at seven days of age, and boosted two weeks later...
October 2018: Molecular and Cellular Probes
Zehua Zhang, Feifan Chen, Jianhua Li, Fei Luo, Tianyong Hou, Jianzhong Xu, Dong Sun
1,25(OH)2 D3 is an immune modulation hormone with beneficial effects on T cell- mediated autoimmune diseases. The purpose of the present study is to investigate the direct effects of vitamin D on Bacillus Calmette Guerin (BCG)-infected CD4+ T cells in both VDR-deficient (VDR-/-) mice and wild type (WT) mice. Specifically, we aimed to investigate the effect of vitamin D on Th1 cells and elucidate the underlying molecular mechanism. Naïve CD4 T cells were purified from VDR-/- mice and WT mice to induce Th1 cells and were activated by BCG...
2018: American Journal of Translational Research
Aravind Shekar, Shylaja Ramlal, Joseph Kingston Jeyabalaji, Murali Harishchandra Sripathy
Escherichia coli O157:H7 with its traits such as intestinal colonization and fecal-oral route of transmission demands mucosal vaccine development. E. coli secreted protein B (EspB) is one of the key type III secretory system (TTSS) targets for mucosal candidate vaccine due to its indispensable role in the pathogenesis of E. coli O157:H7. However, mucosally administered recombinant proteins have low immunogenicity which could be overcome by the use of mucosal adjuvants. The quest for safe, potent mucosal adjuvant has recognized ΔG fragment of Zonula occludens toxin of Vibrio cholerae with such properties...
September 12, 2018: Medical Microbiology and Immunology
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