scholarly journals The Same Combined Adjuvant NE+Rg1 Shows Different Immune Effects on Different Pathogen Antigens 

2021 ◽  
Author(s):  
Pu Shan ◽  
Zhibiao Wang ◽  
Jilai Li ◽  
Duoqian Wei ◽  
Zhuan Zhang ◽  
...  
Keyword(s):  
Viral Infections ◽  
Hepatitis B Surface Antigen ◽  
Haemagglutination Inhibition ◽  
Cell Mediated Immunity ◽  
Immunological Effect ◽  
Protection Rate ◽  
Inactivated Vaccines ◽  
Ifn Γ ◽  
Vaccine Stability ◽  
Nano Emulsion

Abstract Background New recombinant protein vaccines with high purity, clear ingredients and good safety are gradually replacing attenuated and inactivated vaccines in clinical practice. However, one of the main issues with use of these new vaccines is the need for adjuvants to enhance their immune effect. Aluminium salts (hydroxide and phosphate) were the first approved adjuvants used in human vaccines, but these salts have some limitations, such as their induction of primarily humoural immunity with weaker induction of cell-mediated immunity and the failure to clear intracellular viral infections. Therefore, there is a growing need for novel adjuvants. Combined adjuvants or adjuvant systems are increasingly being used to meet the need for adjuvant development for vaccines. Different pathogen antigens also need specific adjuvants to enhance the immune response and protection. Methods The present study evaluated the synergistic immunological effect of a combined nano emulsion (NE) with Ginsenoside Rg1, i.e. NE+Rg1, for the hepatitis B surface antigen (HBsAg) or H1N1 haemagglutinin (HA) of an inactivated influenza vaccine (split virion) in mice and the vaccine stability and safety. Non-parametric tests (Mann-Whitney test) and one-way analysis of variance (ANOVA) were used for statistical analyses. Tests were considered significant when P < 0.05.ResultsThe combined adjuvant NE+Rg1 showed high stability, a mean diameter of 168.1 nm, and a zeta potential of -22.8 mV. When combined with HBsAg, it produced a similar or higher anti-HB and IgG1/IgG2a titre and elevated IL-2 and IFN-γ expression in spot forming cells (SFCs) compared with NE alone and higher IFN-γ and IL-2 expression in CD8+ T cells than aluminium hydroxide. However, when combined with HA, HA+NE+Rg1 resulted in a comparable haemagglutination inhibition (HAI) titre as HA+NE compared to that in mice immunized with HA alone or HA+Rg1 and an even lower protection rate than HA+NE after PR/8/34 virus strain challenge in mice. Conclusions This research demonstrated that the same combined adjuvant NE+Rg1 had different immune effects on different antigens and suggests that the research and development of adjuvants must consider specific pathogens and should be studied on a case-by-case basis.

HCA587 protein vaccine induces specific antitumor immunity mediated by CD4+ T-cells expressing granzyme B in a mouse model of melanoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Weiming Yang ◽  
Weiheng Zhang ◽  
Xiaozhong Wang ◽  
Liming Tan ◽  
Hua Li ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Effect ◽  
Granzyme B ◽  
Cell Subset ◽  
Cell Mediated Immunity ◽  
Protein Vaccine ◽  
Tumor Tissues ◽  
Wide Range ◽  
Ifn Γ

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.

scholarly journals Overt and occult hepatitis B among immigrants and native blood donors in Madrid, Spain

2020 ◽  
Vol 7 ◽  
pp. 204993612098212
Author(s):  
Rocío González ◽  
Luisa Barea ◽  
Ana Arruga ◽  
Alberto Richart ◽  
Vicente Soriano
Keyword(s):  
Hepatitis B ◽  
Viral Infections ◽  
Hepatitis B Surface Antigen ◽  
Developed Countries ◽  
Hcv Rna ◽  
Repeated Testing ◽  
Blood Donations ◽  
Occult Hepatitis ◽  
Hiv Rna ◽  
N 93

Background: The risk of transfusion-transmitted viral infections is very low in developed countries. Recent massive migration flows from highly hepatitis B virus (HBV), hepatitis C virus (HCV) and/or HIV endemic regions to Europe may have changed this scenario. Methods: During 2017 and 2018, a total of 491,753 blood donations (291,762 donors) were evaluated at the Madrid Regional Transfusion Center. All were tested for hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV, as well as for HBV-DNA, HCV-RNA and HIV-RNA. Results: Overall, 35 donors were positive for HIV-RNA and 26 for HCV-RNA. HBV markers were found in 111 (0.022%) donors, split out into three categories: HBsAg+ ( n = 93; 0.019%), occult B infection (OBI) ( n = 17; 0.003%), and acute HBV window period ( n = 1; 0.0002%). All 17 OBI donors were positive for anti-HBc and confirmed as viremic in repeated testing. Viral load amounts were uniformly below 100 IU/mL. Ten OBI donors were repeated donors and look-back studies could be completed for eight of them. Fortunately, none of all prior recipients experienced transfusion transmitted hepatitis B. Compared with HBsAg+ donors, OBI donors were more frequently native Spaniards (76% versus 40%) and older (median age 52 versus 42 years old). Conclusion: Active HBV infection is currently found in 0.022% of blood donations (0.038% of donors) in Madrid. This rate is 3-fold greater than for HIV and/or HCV. On the other hand, HBsAg+ donors are 3-fold more frequent than OBI donors and more often immigrants than native Spaniards. No transfusion-transmitted HBV infections were identified during the study period, including retrospective checking of former recipients of OBI donors.

scholarly journals Towards Improved Use of Vaccination in the Control of Infectious Bronchitis and Newcastle Disease in Poultry: Understanding the Immunological Mechanisms

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 20
Author(s):  
Anthony C. Ike ◽  
Chukwuebuka M. Ononugbo ◽  
Okechukwu J. Obi ◽  
Chisom J. Onu ◽  
Chinasa V. Olovo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease ◽  
Viral Infections ◽  
Advanced Technology ◽  
Global Food Security ◽  
Infectious Bronchitis ◽  
Immunological Mechanisms ◽  
Inactivated Vaccines ◽  
Successful Control ◽  
Cellular Immune

Infectious bronchitis (IB) and Newcastle disease (ND) are two important diseases of poultry and have remained a threat to the development of the poultry industry in many parts of the world. The immunology of avian has been well studied and numerous vaccines have been developed against the two viruses. Most of these vaccines are either inactivated vaccines or live attenuated vaccines. Inactivated vaccines induce weak cellular immune responses and require priming with live or other types of vaccines. Advanced technology has been used to produce several types of vaccines that can initiate prime immune responses. However, as a result of rapid genetic variations, the control of these two viral infections through vaccination has remained a challenge. Using various strategies such as combination of live attenuated and inactivated vaccines, development of IB/ND vaccines, use of DNA vaccines and transgenic plant vaccines, the problem is being surmounted. It is hoped that with increasing understanding of the immunological mechanisms in birds that are used in fighting these viruses, a more successful control of the diseases will be achieved. This will go a long way in contributing to global food security and the economic development of many developing countries, given the role of poultry in the attainment of these goals.

scholarly journals Is the oral microbiome a source to enhance mucosal immunity against infectious diseases?

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Camille Zenobia ◽  
Karla-Luise Herpoldt ◽  
Marcelo Freire
Keyword(s):  
Infectious Diseases ◽  
Oral Mucosa ◽  
Viral Infections ◽  
Emerging Infectious Diseases ◽  
Humoral Response ◽  
Outer Membrane Vesicles ◽  
Oral Microbiome ◽  
Microbial Pathogens ◽  
Cell Mediated Immunity ◽  
Th17 Response

AbstractMucosal tissues act as a barrier throughout the oral, nasopharyngeal, lung, and intestinal systems, offering first-line protection against potential pathogens. Conventionally, vaccines are applied parenterally to induce serotype-dependent humoral response but fail to drive adequate mucosal immune protection for viral infections such as influenza, HIV, and coronaviruses. Oral mucosa, however, provides a vast immune repertoire against specific microbial pathogens and yet is shaped by an ever-present microbiome community that has co-evolved with the host over thousands of years. Adjuvants targeting mucosal T-cells abundant in oral tissues can promote soluble-IgA (sIgA)-specific protection to confer increased vaccine efficacy. Th17 cells, for example, are at the center of cell-mediated immunity and evidence demonstrates that protection against heterologous pathogen serotypes is achieved with components from the oral microbiome. At the point of entry where pathogens are first encountered, typically the oral or nasal cavity, the mucosal surfaces are layered with bacterial cohabitants that continually shape the host immune profile. Constituents of the oral microbiome including their lipids, outer membrane vesicles, and specific proteins, have been found to modulate the Th17 response in the oral mucosa, playing important roles in vaccine and adjuvant designs. Currently, there are no approved adjuvants for the induction of Th17 protection, and it is critical that this research is included in the preparedness for the current and future pandemics. Here, we discuss the potential of oral commensals, and molecules derived thereof, to induce Th17 activity and provide safer and more predictable options in adjuvant engineering to prevent emerging infectious diseases.

scholarly journals Current Status of Zika Virus Vaccines: Successes and Challenges

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 266 ◽  
Author(s):  
Aryamav Pattnaik ◽  
Bikash R. Sahoo ◽  
Asit K. Pattnaik
Keyword(s):  
Zika Virus ◽  
Viral Infections ◽  
Current Status ◽  
Effective Vaccine ◽  
Congenital Diseases ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Funding Agencies ◽  
Inactivated Vaccines

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.

scholarly journals Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2091
Author(s):  
Ana Sara Cordeiro ◽  
Yogita Patil-Sen ◽  
Maitreyi Shivkumar ◽  
Ronak Patel ◽  
Abdulwahhab Khedr ◽  
...  
Keyword(s):  
Clinical Application ◽  
Viral Infections ◽  
Downstream Processing ◽  
Delivery Systems ◽  
Regulatory Requirements ◽  
Dose Frequency ◽  
Socioeconomic Impacts ◽  
Recent Success ◽  
Different Types ◽  
Vaccine Stability

Viral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians.

scholarly journals A 70-Kilodalton Recombinant Heat Shock Protein ofCandida albicans Is Highly Immunogenic and Enhances Systemic Murine Candidiasis

1998 ◽  
Vol 66 (5) ◽  
pp. 2154-2162 ◽  
Author(s):  
Carla Bromuro ◽  
Roberto La Valle ◽  
Silvia Sandini ◽  
Francesca Urbani ◽  
Clara M. Ausiello ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Mononuclear Cells ◽  
Cell Mediated Immunity ◽  
Healthy Human ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-γ), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-γ was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-γ upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.

scholarly journals Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 715
Author(s):  
Chunxiang Bai ◽  
Lijun Zhou ◽  
Junxia Tang ◽  
Juanjuan He ◽  
Jiangyuan Han ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Central Memory ◽  
Control Group ◽  
Cell Mediated Immunity ◽  
Protein Subunit ◽  
Subunit Vaccines ◽  
Ifn Γ

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is among the most serious infectious diseases worldwide. Adjuvanted protein subunit vaccines have been demonstrated as a kind of promising novel vaccine. This study proposed to investigate whether cytokines interliukine-7 (IL-7) and interliukine-15 (IL-15) help TB subunit vaccines induce long-term cell-mediated immune responses, which are required for vaccination against TB. In this study, mice were immunized with the M. tuberculosis protein subunit vaccines combined with adnovirus-mediated cytokines IL-7, IL-15, IL-7-IL-15, and IL-7-Linker-IL-15 at 0, 2, and 4 weeks, respectively. Twenty weeks after the last immunization, the long-term immune responses, especially the central memory-like T cells (TCM like cell)-mediated immune responses, were determined with the methods of cultured IFN-γ-ELISPOT, expanded secondary immune responses, cell proliferation, and protective efficacy against Mycobacterium bovis Bacilli Calmette-Guerin (BCG) challenge, etc. The results showed that the group of vaccine + rAd-IL-7-Linker-IL-15 induced a stronger long-term antigen-specific TCM like cells-mediated immune responses and had higher protective efficacy against BCG challenge than the vaccine + rAd-vector control group, the vaccine + rAd-IL-7 and the vaccine + rAd-IL-15 groups. This study indicated that rAd-IL-7-Linker-IL-15 improved the TB subunit vaccine’s efficacy by augmenting TCM like cells and provided long-term protective efficacy against Mycobacteria.

Vaccination of broilers against Newcastle disease in the presence of maternally derived antibodies

2017 ◽  
Vol 45 (03) ◽  
pp. 151-158 ◽  
Author(s):  
Máté Halas ◽  
Tamás Süli ◽  
Anto Vrdoljak
Keyword(s):  
Newcastle Disease ◽  
Haemagglutination Inhibition ◽  
Local Immunity ◽  
Live Attenuated Vaccine ◽  
Post Vaccination ◽  
Attenuated Vaccine ◽  
Protection Rate ◽  
Virulent Virus ◽  
Important Means ◽  
Test Points

Summary Objective: The aim of this study was to evaluate the efficacy of a live attenuated vaccine against Newcastle disease in broilers with different levels of maternally derived antibodies (MDA). While vaccination remains the single most important means for controlling Newcastle disease, presence of MDA may interfere with the vaccination of young birds and decrease the efficacy of the vaccine. Materials and methods: Day-old chicks with variable levels of MDA (negative, low and high) were vaccinated with a live attenuated vaccine against Newcastle disease. Three most commonly used inoculation routes were compared; oculonasal, spray and oral (drinking water). Onset and duration of immunity were measured by serology and challenge with virulent virus. Results: Immune response in vaccinated MDA-positive birds was delayed in comparison with SPF controls. Protection was well established already at 14 days post vaccination in SPF birds while in MDA-positive birds it was 1–2 weeks delayed and was lower throughout the study. Non-vaccinated MDA-positive birds lost passive protection completely at 3–4 weeks of age and were significantly more susceptible to challenge than vaccinated hatch mates at all test points. The protection rate increased in vaccinated birds towards the end of the experiment and reached 70–100 % at the last test points (35–42 days of age). Correlation of haemagglutination inhibition (HI) titre vs. protection rate revealed the importance of cellular and local immunity as most of the vaccinated birds with low HI titre were protected, contrary to their unvaccinated hatch mates with the same HI titre. Oculonasal route seems to provide slightly better protection than the other two routes. Conclusions and clinical relevance: Although immune protection in vaccinated MDA-positive birds may be decreased or delayed, vaccination still provides high protection against ND challenge in comparison with the unvaccinated hatch mates. The degree of interference seems to be proportional to the level of MDA. Vaccination schedules therefore need to be designed according to the immune status of the flock.

Sign in / Sign up

Export Citation Format

Share Document