Immunogenicity Research Articles

Cultural Artefacts with Virtual Capabilities Enhance Self-Expression Possibilities for Children with Special Needs.

In this paper we discuss how new combinations of technology, art and culture enable children with special needs new ways to express themselves. UN declaration (UDHR) states "All human beings have the right to participate in cultural life, enjoy art…", later including children (CRC) and persons with disabilities (CRPD). To meet these UN demands, several countries have created cultural programs to offer children art and culture activities in school. In the Norwegian Cultural Schoolbag-program they emphasize that art and culture can provide experiences that may be decisive in order to develop the individual's personal identity, life quality and alternative worldviews. Since 2015 one county offers a unique "Accessible-Program" for children with special needs. From many years of research, we know the health-promoting value of artistic and musical activities. New technology opens up completely new ways to make art and culture accessible for all. In this paper, we show how we used music and cultural artefacts with musical and visual capabilities (RFID, AI), giving diverse users new musical, artistic, sensorial and creative experiences. We do this in relation to Ruud's concepts of Health Affordance and Cultural Immunogen. As a travelling interactive art installation, being part of the Norwegian "Accessible-Program", we made participatory observations in six schools. We experienced how the children expressed themselves, co-created, showed self-efficacy and made different cultural experiences, depending on disability and relations. With this paper, we emphasize that art and culture, in combination with technology, offers valuable new health-promoting potentialities, important for the UD community.

AAV Immunogenicity: New Answers Create New Questions.

AAV Immunogenicity: New Answers Create New Questions.

Canine Blood Groups: a review

This literature review aims to discuss the major blood types of dogs and the particularities of each system, in order to help clinicians to carry out correct blood transfusion procedures and to ensure good survival chances to the patients. DEA groups ( Dog Erithrocyte Antigens) 1.1, 1.2, 1.3, 3, 4, 5, 6, 7, 8, Dal and Shigeta will be reviewed, with their respective prevalences and its immunogenic characteristics. It is concluded that some canine erythrocyte antigens have higher antigenicity and may cause a major hemolytic reaction, reducing the therapeutic action of blood transfusion or its components in dogs.

Effects of different concentrations of aluminum hydroxide adjuvant and adsorption methods on the immunogenicity of diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine (DTaP-sIPV). Methods Five antigens of DTaP were adsorbed onto different concentrations (0.42 mg/ml, 0.47 mg/ml and 0.52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin (PT)/filamentous hemagglutinin (FHA)/pertactin (PRN)/diphtheria toxoid (DT)/tetanus toxoid (TT) antibodies and the potency of vaccines were detected. Results The adsorbability of aluminum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no significant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0.52 mg/ml and separate adsorption method are suitable for preparation of DTaP-sIPV. Key words: DTaP-sIPV; Adsorbability; Vaccine potency; Anti-pertussis toxin (anti-PT) antibody; Anti-filamentous hemagglutinin (anti-FHA) antibody; Anti-pertactin (anti-PRN) antibody; Anti-diphtheria toxoid (anti-DT) antibody; Anti-tetanus toxoid (anti-TT) antibody

Candidate TB Vaccine Protects TB-Infected Adults Against Active Pulmonary TB

The M72/AS01E candidate vaccine against tuberculosis (TB) combines two immunogenic Mycobacterium tuberculosis antigens with the AS01 adjuvant system.

AAV Immunogenicity: A Matter of Sensitivity.

AAV Immunogenicity: A Matter of Sensitivity.

Advances in methods for evaluating clinical immunogenicity of human papillomavirus vaccines

Human papillomavirus (HPV) infection is the most common sex-transmitted virus infection. Persistent infection of HPV could cause cancers in different parts of the body, such as cervix and anus. Up to now, three prophylactic HPV vaccines have been approved to prevent HPV infection and related diseases. It is well accepted that neutralizing antibodies are the mediator of protection. Analysis of immunogenicity has been playing a key role in HPV vaccine clinical trials, especially in the evaluation of durability of immune responses, immunobridging in young girls and boys, and reduced-dose schedules. There is still no unique method for the evaluation of immunogenicity of HPV vaccines in clinical trials. The data of immunogenicity from different clinical trials cannot be compared directly. It is urgently needed to establish a high throughput and protection-related unique assay as well as standard materials for its standardization. To accelerate the development and evaluation of prophylactic HPV vaccines, a standardized method should be well validated and transferred to different laboratories to make clinical immunogenicity data comparable. Key words: Human papillomavirus; Clinical trial; Immunogenicity; Neutralizing antibody

Validation of a pseudovirus-based neutralization assay for detection of human papillomavirus antibodies in human serum samples

Objective To validate a pseudovirus-based neutralization assay for the detection of antibodies against human papillomavirus (HPV) in human serum samples. Methods The specificity, accuracy, precision, range of linearity, limit of detection and robustness of the neutralization assay were evaluated using HPV-negative serum samples, vaccinated serum samples with quadri-valent vaccine, and international standards for detecting antibodies against HPV16 and HPV18. Results Based on the data of the HPV-naive samples, the criteria of positivity was determined as follows: the 50% inhibitory dose (ID50) of the tested sample was not less than 40 and 2-fold not less than that for bovine papillomavirus. The neutralization assay showed good accuracy with a recovery rate of 87%-122% and excellent reproducibility with intra- and inter-assay variation of 5%-27% and 10%-26% respectively. The HPV16 and HPV18 international standards were used to define the limit of quantification, which was 1.28 IU/ml for HPV16 and 0.96 IU/ml for HPV18. Acceptable ranges of variation for the key parameters of this assay were defined, which showed the good robustness of the pseudovirus-based neutralization assay. Conclusion The pseudovirus-based neutralization assay for the detection of HPV antibodies showed good specificity, accuracy, sensitivity, and robustness, suggesting that it could be used to evaluate the immunogenicity of HPV vaccines. Key words: Human papillomavirus; Neutralizing antibody; Validation

Tumor immunotherapy—the potential of epigenetic drugs to overcome resistance

Immune checkpoint inhibitors recently introduced into clinical practice have enriched available treatment options for a number of solid cancers. The efficacy of these treatments may however be impaired by tumor cell-intrinsic factors and tumor cell-extrinsic factors resulting in repressed tumor immunogenicity and host immune response. Accordingly, only a subgroup of patients responds to this treatment. Epigenetic drugs may offer an exciting novel approach to reverse immune suppression and to ‘prime’ tumors for immunotherapy, as DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors and bromodomain and extra-terminal motif (BET) inhibitors show immunomodulatory properties by affecting both cancer cells directly as well as the tumor microenvironment. Upregulation of tumor associated antigens (TAAs), ligands for natural killer (NK) cell receptors, chemokine expression, altered immune checkpoint molecules, antigen procession and presentation as well as induction of viral mimicry improve recognition of cancer cells. In the tumor microenvironment, suppression of myeloid-derived suppressor cells (MDSCs), modulation of regulatory T cells function and activation of NK cells may improve immunogenic efficacy. In conclusion, current preclinical data supports translation of combinatorial treatment approaches into clinical trials and practice.

Relationship between oncolytic viral therapy and tumor microenvironment or body immunity

The interaction between oncolytic virus (OV) and the tumor microenvironment or body immune system is critical to the outcome of antitumor therapy. The antitumor mechanism of OV is complex, which involves direct cytotoxic effects, immunogenicity change in tumor microenvironment, the role of tumor vasculature, and activating of the antitumor immunity response, to reach the goal of killing the tumor cells infected or uninfected, and confirming the continous favorable effects. Key words: Oncolytic viruses; Tumor microenvironment; Immunotherapy

Correction: Resistance to anticancer vaccination effect is controlled by a cancer cell-autonomous phenotype that disrupts immunogenic phagocytic removal.

[This corrects the article DOI: 10.18632/oncotarget.4754.].

Subyearling Siberian Sturgeon Acipenser baeri Fed a Diet Supplemented with ImmunoGen: Effects on Growth Performance, Body Composition, and Hematological and Serum Biochemical Parameters.

In this research, the effect of ImmunoGen (IMNO) on the growth indices, hematological parameters, and carcass composition of Siberian Sturgeon Acipenser baeri was investigated. After acclimation, fish (274.8±16.2g) were allocated into 12 tanks (10 fish per tank) and triplicate groups were fed a control diet (0%) or diets containing 0.5, 1.0, or 1.5% IMNO for 75d. At the end of the experiment, final length, final weight, and weight gain were significantly higher in the fish fed the diet containing 1.0% IMNO, though no significant differences were observed between the control and experimental diets containing 0.5% and 1.5% IMNO. In addition, there were no significant differences among diets in terms of hematological parameters and carcass composition. However, dietary IMNO significantly affected the serum biochemical parameters of Siberian Sturgeon, such as cholesterol, triglycerides, and IgM, with the highest level of IgM occurring in the 1.0% IMNO treatment and the lowest levels of cholesterol and triglycerides in the 1.5% IMNO treatment. The findings of this study thus indicate that the administration of 1.0% IMNO in diet positively affects the growth factors and some serum biochemical parameters of Siberian Sturgeon.

Research progress of aptamer and organic nanomaterials based tumor targeting drug delivery systems

Aptamers are DNA or RNA fragments that can specifically bind to target substances. Because of the excellent properties such as strong binding force, high specificity, small physical size, chemical synthesis and modification, good biocompatibility, and low immunogenicity aptamers show wide application propects in biomedical researches. Aptamers can also bind specifically to receptors on the surface of cell membranes, and mediate the endocytosis of nanoparticles into cells, making them ideal drug targeting ligands. Organic nanomaterials have excellent application value in nanodrug delivery system because of their good biocompatibility and degradability. In this paper, the recent research progress of aptamers and organic nanomaterials drug delivery systems was reviewed. Key words: Aptamers; Organic nanomaterials; Targeting delivery system

Cartilage/chondrocyte research and osteoarthritis. Regeneration of articular cartilage damage using iPS cell-derived cartilage.

Induced pluripotent stem (iPS)cells have capacities of self-renewal and pluripotency. We have developed a method to differentiate human iPS cells toward chondrocytes, followed by the creation of cartilage tissue composed of chondrocytes and cartilage extracellular matrix. The mechanism through which tissue transplantation repairs cartilage defects involves the transplant itself constituting the repair tissue. Human iPS cell-derived cartilage has low immunogenicity and can be transplanted in an allogeneic manner. We are conducting pre-clinical tests on iPS cell-derived cartilage to verify efficacy and safety that will act as a basis for clinical tests.

Diagnosis and treatment of rheumatoid arthritis:toward the best practice. The best practice for TNF inhibitors.

As of February 2018, 5 originator TNF inhibitors(infliximab, etanercept, adalimumab, golimumab and certolizumab pegol)and biosimilar agents of infliximab and etanercept are available for rheumatoid arthritis(RA)in Japan. The effectiveness of TNF inhibitors considerably improves with concomitant methotrexate regardless of their immunogenicity. The Japan College of Rheumatology guideline for TNF inhibitor use in RA has been updated in March 2017 according to recent evidences. During the remission induction phase, maintenance of drug trough level above effective blood concentration is paramount, while the tapering and withdrawal of TNF inhibitors may be considered after achieving sustained remission.

Immunogenicity and safety of a booster dose of live attenuated measles-mumps-rubella vaccine for 4-year-old children

Objective To evaluate the immunogenicity and safety of a booster dose of live attenuated measles-mumps-rubella (MMR) vaccine for 4-year-old children and to provide references for reasonable arrangement of MMR immunization schedule. Methods Children aged 4 years (54-60 months) old were recruited and divided into three groups as follows: Group 8 months MR [receiving live attenuated measles and rubella (MR) vaccination at 8 months and MMR vaccination at 18 months], Group 8 months MMR (receiving MMR vaccination at both 8 and 18 months) and Group 12 months MMR (receiving MMR vaccination at both 12 and 22 months). Active follow-up was conducted for safety evaluation after immunization of all subjects with the booster dose of MMR vaccine. Blood samples were collected before and 35 days after vaccination and analyzed by ELISA to detect serum antibodies to measles, mumps and rubella. Results A total of 514 subjects were enrolled in this study of safety evaluation and 469 of them received serologic detection of antibodies twice. The rate of adverse reactions following vaccination was 17.12% (general reactions accounted for 94.21%) and no severe adverse reactions were reported. No significant difference in the rates of adverse reactions was found among the three groups (χ2=4.82, P=0.090). Subjects who were seropositive for measles, mumps and rubella increased after immunization with MMR vaccine, accounting for 100%, 99.79% and 99.79%, respectively. Geometric mean concentrations (GMC) against measles, mumps and rubella in all subjects were 1.35, 3.05 and 2.13 times higher than what they were before the immunization. Levels of antibodies to measles, mumps and rubella were all increased significantly in the three groups after immunization with the booster dose of MMR vaccine (Fisher Exact Test, P=0.000). Conclusion The booster dose of MMR vaccine increases the levels of serum antibodies in children aged 4 years old with high safety. It suggests that two doses of MMR vaccine should be encouraged in the immunization program in China. Key words: MMR vaccine; Immunogenicity; Safety

Research progress of neonatal hypoxic-ischemic encephalopathy treatment with mesenchymal stem cells

Neonatal hypoxic-ischemic encephalopathy (HIE) can result in serious outcomes including death during the newborn period and later neuropsychological handicaps.So far, there have been no obvious effect on the improvement of prognosis with traditional treatments, and the cryogenic treatment is the most effective treatment for the past decade, while the clinical application is limited by age and disease course.At present, stem cell transplantation in the treatment of HIE is the new direction, of which the mesenchymal stem cells are outstanding by its easy materials, low immunogenicity and potential nerve regeneration properties.This paper reviews and updates the progress of mesenchymal stem cell transplantation for neonatal HIE. Key words: Cell therapy; Mesenchymal stem cell; Neonatal hypoxic-ischemic encephalopathy

Interstitial lung diseases associated with metal content in silicone breast implants: a case series.

Background: Silicone gel-filled breast implants have been widely used for breast augmentation and reconstruction since the 1960’s when the FDA approved them in women over 22 years of age. Concerns have been raised about the safety of those implants, with the focus upon whether silicone leak can spread to regional lymph nodes and remote organs and possibly cause inflammatory and immune responses. Objective: To present laboratory workup findings in 3 cases of interstitial lung diseases (ILD) linked with silicone implant leakage. Methods: ILD was diagnosed by tissue biopsy and Computerized Tomography (CT). We analyzed the metal content in both biological samples and raw material of the implants by means of scanning electron microscopy (SEM) and X-ray fluorescence (XRF). The metals lymphocyte proliferation analysis (MELISA®) was used to assess sensitization of the immune system to 19 metals. Results: The biological samples contained metals (silicon, nickel, zinc, tungsten, iron, aluminum, and zirconium) which are also present in the silicone implant. The MELISA test showed sensitization to nickel, zinc and tin. Limitations: Some of the immunogenic metals present in the implant were under the limits of detection of SEM and XRF and the sensitivity of MELISA test is unknown. Conclusions: The laboratory assessments of the 3 herein described women indicated that their interstitial lung disease was associated with the metal content of their silicone gel-filled breast implantations. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 381-389)

Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent

목적: 인플루엔자 유행 예방에 대한 가장 효과적인 방법은 인플루엔자 백신이나 한국의 소아청소년을 대상으로 한 면역원성 및 안전성에 대한 자료가 많지 않다. 이에 본 연구는 국내에서 많이 사용되는 불활성화 3가 백신의 면역원성과 안전성을 확인하고자 하였다. 방법: 2008년 10월부터 12월까지 고려대학교 의료원 안산병원 소아청소년과에 인플루엔자 예방접종을 위해 내원한 건강한 소아청소년 중 임상시험 지원자 65명을 대상으로 하여 접종 전과 접종 후 30일째 혈구응집억제(hemagglutinin inhibition) 항체검사를 시행하고 접종 직후부터 접종 후 7일까지 국소반응과 전신반응을 포함한 이상반응을 관찰하여 기록하도록 하였다. 결과: 분할 인플루엔자 백신의 세 항원(H1N1, H3N2, B) 각각에 대한 접종 후 혈청보호율은 87.7%, 89.2%, 89.2% (≥70%)였으며 혈청전환율은 44.6%, 73.8%, 63.1% (≥40%), 혈청전환인자는 3.35, 7.18, 5.13 (>2.5)으로 Committee for Proprietary Medicinal Products (CPMP) 기준을 만족하였다. 전체 피험자 65명 중 48명(73.8%)이 백신 접종 후 이상반응을 보고하였으나 아나필락시스나 경련과 같은 심각한 이상반응은 없었다. 발적(29.2%), 동통(43.1%), 종창(41.5%)과 같은 국소반응을 보고한 피험자는 42명(64.6%)이었고, 권태(23.1%), 근육통(20.0%), 두통(10.8%), 관절통(10.8%), 오한(9.2%), 발열(7.7%) 등과 같은 전신반응을 보고한 피험자는 26명(40.0%)이었다. 결론: 6개월에서 18세까지의 소아청소년을 대상으로 한 불활성화 3가 백신의 면역원성과 안전성에 대한 연구 결과 H1N1, H3N2, B 항원 모두 CPMP 기준에 부합하여 적합한 면역원성이 있는 것으로 나타났으며, 국소반응 및 경미한 전신반응 이외에 심각한 이상반응은 보이지 않아 비교적 안전하다고 판단된다.

Mycobacterium avium Complex Extracellular Vesicles Attenuate Inflammation via Inducing IL-10.

Mycobacterium avium complex (MAC) is an ubiquitous acid-fast bacterium. MAC cell wall and membrane release extracellular vesicles (EVs) into different media. The immunogenic effects of EVs isolated from MAC remain unknown. The aim of this study was to determine the EVs effect on macrophage cytokine production. MAC EVs were extracted and purified using differential centrifuges also known as Claassen’s method, with some modifications. After protein analysis of EVs, and scanning electron microscopy (SEM), the EVs were injected into BALB/c mice for in vivo experiments. The concentration of interferon gamma (IFN-γ) and interleukin 10 (IL-10) in the spleen immune cell culture was measured by sandwich ELISA. We for the first time showed that MAC can naturally produce EVs. The extraction method was technically-feasible, efficient and affordable. The SEM analysis showed that EVs diameter was similar to other studies on mycobacteria, and EVs maintained their spatial characterization. The results of the cytokine assays indicated that EV-treated cells secreted IL-10 (P = 0.034) but not IFN-γ (P = 0.037). Our findings suggest that EVs of M. avium could have anti-inflammatory effects. They can be used as a suppressor or regulator of inflammation via IL-10. The replication of the anti-inflammatory response of MAC EVs in future studies may indicate a new therapeutic agent for inflammation.