1Research Center of Molecular Diagnostics, Russia
Prophylactic of infectious diseases by live vaccines were the most successful events in the struggle against viruses and bacteria in the XX century. Small pox, poliomyelitis and tuberculosis were taken under control by wide application of corresponding live vaccines.
We suggested that live vaccine for oncology could be live xenogeneic tumor. Mouse models have shown that xenotransplantation of tumors are safe for recipients with normal immunity. Moreover, unsuccessful xenotransplantation is very successful immunization.
Xenotransplantation of tumors, widely used in experimental oncology, is successful only in immunodeficient mouse models but can be used as powerful immunization tools for creation of anti- tumor immunity in normal subjects. We have shown significant protection for mouse melanoma B-16, when we vaccinated animals with human Sk-Mel -1 melanoma cells transplanted into connective tissue capsule. Xenogeneic transplantation of mouse melanoma cells to humans healthy volunteers – authors of this presentation, have shown raise of serum antibodies against common human/ mouse melanoma antigens, s-100 and GM-3, by ELISA. T-cells anti-melanoma response was detected by gamma-interferon Elispot test. Local immunity, immediate and delayed types, against mouse B-16 melanoma was present in the course of this xenogenic anti-tumor vaccination.
Classical vaccination according to Sir Edward Jenner means prophylactics but in oncology, there is a great will to apply vaccines for therapeutic purposes. In case of melanoma, one point of application for prophylactic vaccine is post surgical immunization to prevent future metastasis. It is especially important for uveal melanoma; where primary tumor is removing with the completely affected organ – eye and metastasis usually appear in lungs and liver several years after surgery.
In the frame of Phase 1 clinical trial of xenovaccination for melanoma, approved by Russian Ministry of Health, vaccination of uveal melanoma patients with live mouse melanoma B-16 was started in 2004. 35 patents with stage T2-4 N0M0 uvelal melanoma were vaccinated with 100 mln, mouse melanoma cells by injection into connective tissue capsule preliminary formed by subcutaneous injection of biocompatible gel. 5 patients have got metastasis with in the first 18 months of observation. The rest 30 patients are free from melanoma up today.
USTHB, Algeria
Scorpion envenomation is a major public health problem encountered in tropical and subtropical countries such as North Africa, Central and South America, the Middle East, and South Asia. The severity of this accidental pathogenesis is due to the massive release of sympathetic and parasympathetic neurotransmitters, which leads to hemodynamic changes associated to cardiogenic shock and pulmonary edema leading to the death. Right now, the only available specific treatment is the serotherapy which remains limited due, not only to its low efficiency, but also to the delay of its administration. Vaccine could be a promising alternative to this therapy. This approach must be developed in compliance with bioethical rules requiring the use of the highly immunogenic yet biocompatible preparations. In this study, the immunogenic effect of TiterMax Gold (TMG) adjuvant associated to irradiated Androctonus australis hector venom was compared to commonly used Freundʼs complete adjuvant preparation. The obtained results showed that this formulation using TMG in the immunization of animals results in low activation of granulocyte cells as well as their related peroxidase activities while the immunized animals with FCA adjuvant present signs of chronic inflammatory response. The specific immune response triggered by this vaccine showed that attenuated venom associated to TMG are highly efficient resulting in high specific titers of antibodies, mainly those of IgG1 subclass, suggesting a potent activation of the humoral immune response by this adjuvant. The evaluation of immunoprotective effect against the native venom showed that TMG preparation was able to protect animals up to 5 LD50 of native venom while FCA preparation was limited to 3 LD50.
Moreover, the histological analysis of pulmonary and cardiac tissues of immunized animals with the TMG formulation and survived to the high doses of native venom showed no alterations compared to those immunized with FCA, providing more evidence to the potent immunoprotection conferred by TMG preparation. Altogether, these results give an insight on the harmlessness and the potency of this newly described adjuvant in the induction of a long lasting specific immunoprotection against scorpion envenoming compared to a classic adjuvant.
Keywords: Scorpion envenomation, TiterMax Gold, Vaccination, immunoprotection.
1The Centers for Disease Control and Prevention, USA
2Uganda National Expanded Program on Immunization, Uganda
3African Field Epidemiology Network (AFENET) Secretariat, Uganda
4The Bill & Melinda Gates Foundation, Seattle, USA
Building health workforce capacity is a key strategy to achieve the Global Vaccine Action Planʼs goal of strengthening routine immunization systems to boost plateauing vaccination coverage. The Strengthening Technical Assistance for Routine Immunization Training (START) approach was designed to utilize practical training methods to develop skills of both district and health facility staff to implement key planning and monitoring activities for routine immunization as well as build supportive supervision skills of district staff. First implemented in Uganda, the approach was executed by trained external consultants who mentored district-level staff and with them, conducted on-the-job training for health facility staff. The START approach was designed to be flexible and adaptable to meet district needs, while adhering to the implementation principles of; use of practical on-the-job training and mentoring; focus on key elements of RI planning and monitoring, and revisits. Routine monitoring of the approach focused on processes, outputs and short-term changesresulting from START consultantsʼwork. From July 2013 through December 2014 three START teams of four consultants per team, worked 5.5 months each across 50 districts (45%) and five divisions of Kampala in Uganda. They conducted on-the-job training in 444 selected under-performing health facilities, with a median of two visits to each (range 1 – 7). More than half of these visits were conducted in collaboration with the district immunization officer, providing the opportunity for practice and mentorship for district immunization officer to conduct on-the-job training for health facilities. Changes in staff motivation, awareness of challenges, and completion of planning and monitoring tools were observed at both district and health facility levels. However, potential for sustainability of these, and newly introduced processes, were felt to be limited by numerous contextual factors, including external accountability, availability of resources, and individual staff motivation. Despite such limitations, mentoring and on-the-job training are promising alternatives to traditional classroom training for improving immunization program staff performance.
keywords: workforce development, training, immunization, vaccination, program evaluation, expanded program for immunization
Dyadic Inc., USA
Dyadic International, Inc. is a global biotechnology company which is developing a potentially significant biopharmaceutical protein production system based on the fungus Myceliophthora thermophila, nicknamed C1.
The C1 microorganism is being developed into a safe and efficient expression system that may help speed up the development, production and performance of biologic vaccines and drugs.
Dyadic is using the C1 technology to conduct research, development and commercial activities for the development and manufacturing of human and animal vaccines, monoclonal antibodies, and other therapeutic proteins.
Dyadic pursues research & development collaborations, licensing arrangements and other commercial opportunities with its partners and collaborators to leverage the value and benefits of these technologies in developing and manufacturing biopharmaceuticals which these technologies help produce.
In particular, as the aging population grows in developed and undeveloped countries, Dyadic believes the C1 technology may help bring biologic drugs to market faster, in greater volumes, at lower cost, and improve access and cost to patients and the healthcare system, but most importantly save lives.
1Department of Hepatobiliary Surgery, Fuzhou General Hospital of Fujian Medical University, China
2Department of Hepatobiliary Surgery, Fuzhou General Hospital, China
3Fujian University of Traditional Chinese Medicine, China
4Department of Hepatobiliary Surgery, China
Heterogeneous ribonucleoprotein (hnRNPA1) is a documented tumor biomarker known to be aberrantly expressed in many human cancers. However, to our knowledge, its prognostic value for surgically resected hepatocellular carcinoma (RHCC) for high incidence areas of China has not been described and relationship among hnRNPA1 expression, preoperative NLR and PLRhas notunderstood. Methods: We retrospectively measured hnRNPA1 expression in twoindependent cohorts of HCC patients who underwent surgery to remove the primary cancer at one center in Fujian, China, an area with a high incidence of HCC. quantitative reverse transcription-polymerase chain reaction (qRT-RCR), western blot analyses and immunohistochemistry (IHC) were used to quantify hnRNPA1 expression in surgically RHCC tissues. The survival curves were estimated by Kaplan-Meier analysis and the prognostic significance of hnRNPA1, Neutrophils to lymphocytes(NLR)and platelets to lymphocytes(PLR) were analyzed using the log-rank test. The identification of relevant prognostic factors was performed by multivariate Cox regression analysis. Results: Both qRT-RCR and western blot analyses revealed that hnRNPA1 was upregulated in HCC tissues. hnRNPA1 was overexpressed in tumor tissues of patients with recurrent HCC (cohort one,54 patients).Differential hnRNPA1 expression was measured in 426 tissues from HCC by immunohistochemistry(IHC). Among them 259 showed high hnRNPA1expression, whereas the other 167 had low expression of hnRNPA1. High hnRNPA1 was significantly related to Preoperative serum α-fetoprotein (AFP) > 400 μg/L (p <0.001), NLR (p < 0.001) and PLR (p < 0.001). Moreover, multivariate Cox regression analysis confirmed that high hnRNPA1 expression was strongly associated with disease-free survival (DFS) (HR,2.009; 95% CI,1.473-2.739; p < 0.001) and overall survival (OS) (HR,2.412; 95% CI,1.864-3.455; p <0.001). Multivariate analysis confirmed that higher preoperative serum AFP had an unfavorable impact on OS (HR,1.573; 95% CI,1.163-2.127; p=0.003); higher preoperative NLR had an unfavorable impact on OS (HR, 1.911; 95% CI, 1.280-2.851; p=0.002) (cohort two,426 patients). Conclusions: High hnRNPA1 expression has prognostic value for poor survival for RHCC patients, and detection of hnRNPA1 with IHC may be promising for estimating survival for RHCC patients in areas with high-incidence for this disease in China. hnRNPA1 expression and preoperative serum AFP (> 400μg) offer a better biomarker for our specific population. there may be a correlation between hnRNPA1 expression and biological markers of systemic inflammation.
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