Day 1 full schedule
August 11, 2021 @ -
Intramammary vaccine delivery counteracts mammary tumor growth more efficiently than systemic vaccine delivery
San Raffaele Roma Open University
The effectiveness of cancer vaccines is greatly dependent on the type of vaccine used, antigens employed, and route of administration. Using the BALB-neuT mouse model, we explored the mammary tumor inhibitory ability of a recombinant vaccinia virus (rV-neuT), encoding for a specific tumor antigen (neu), administered both locally, into the mammary fat pad, and systemically, subcutaneously. The BALB-neuT model express Neu, the rat homologue of the human ErbB2. Tumor masses spontaneously develop in the mammary glands of female mice, with a precise disease evolution over time. This characteristic was therefore exploited to determine whether the rV-neuT vaccination efficiency was dependent on the carcinogenesis stage at which the vaccination was initiated and on the use of multiple rV-neuT injections, as compared to wild type vaccinia virus (V-wt). Our findings indicate that rVneuT intramammary gland vaccination is superior in inhibiting the neu oncogene-mediated mammary carcinogenesis in comparison to subcutaneous vaccination. When vaccination started at an earlier stage of disease a better tumor suppression was obtained, while regression of established tumor was less effective using later vaccination. Moreover, the dose response study confirmed that a better tumor free survival was obtained with multiple vaccinations as compared to a single shot. Tumor growth was more efficiently inhibited by anti-Neu antibodies elicited with rV-neuT vaccinations. Antibody-dependent cellular cytotoxicity and apoptosis were induced by high titer of antibodies, while T cell proliferative response to Neu peptides was similar between intramammary and subcutaneous rV-neuT vaccine administration. These results suggest that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus.
In vivo inhibition of the growth of salivary glands carcinoma cells by recombinant vaccinia Neu vaccine (rV-neuT) and curcumin
Saint Camillus International University of Health and Medical Sciences
Head and neck carcinomas (HNC) represent one of the most fatal cancers worldwide and despite improvements in treatment, the survival rate of HNC patients has not changed in the last two decades. Salivary gland carcinomas are HNC with heterogeneous morphology, which overexpress ErbB2. These tumors are suitable for intratumoral delivery of cancer vaccines. Vaccination with engineered attenuated recombinant vaccinia virus has been employed in clinical trials, which highlighted the safety of the vaccine and the induction of specific humoral and T cell responses against the tumorassociated antigen in cancer patients. We evaluated the efficacy of intratumoral vaccination with the recombinant vaccinia virus ErbB2/Neu (rV-neuT) vaccine in hampering the growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells (SALTO) in syngeneic BALB-neuT mice. Two rV-neuT intratumoral injection rejected the growth of SALTO cancer cells in mice and rV-neuT vaccinated mice Igs mediated ADCC, down-regulated ErbB2/Neu receptor, inhibited ERK1/2 phosphorylation, and induced apoptosis of SALTO cells in vitro. However, reiterated poxviral vaccinations increase neutralizing antibodies to viral proteins in humans that prevent immune response against the recombinant antigen expressed by the virus. Hence, we employed Curcumin (CUR), a polyphenol with antitumoral and immunomodulatory properties, to boost the anti-Neu immune response and anticancer activity induced by one rVneuT intratumoral vaccination in BALB-neuT mice. The combined rV-neuT+CUR treatment resulted more effective at reducing tumor growth, increasing mouse survival, anti-Neu humoral response, IFN-γ/IL-2 T-cell release in vitro, and increasing infiltration of CD4+/CD8+ T lymphocytes within the tumor of rV-neuT+CUR-treated mice, as compared to single treatment. Thus, the antitumoral effect and immune response to Neu induced by the rV-neuT vaccine was increased by CUR in mice. Our studies suggest that intratumoral vaccination using recombinant vaccinia virus in combination with CUR might represent a novel strategy for the treatment of ErbB2/Neu-overexpressing tumors, like salivary glands carcinomas.
Synergist and Antagonist In-vitro Carbonic Anhydrase Inhibition of Botulinum Toxin and Bee Venom Under Simulated Mars Atmosphere
Ozan Emre EYUPOGLUAssistant Professor
School of Pharmacy at Istanbul Medipol University
Sulfonamides, anions, and sulfamate class inhibitors are compounds with inhibitory potential in-vitro and in-vivo carbonic anhydrase studies . Various proteins and peptides isolated from bee venom include phospholipase A2, melittin, secapine, bradykinin, cardiopep, adiapine, mastoparan and apamine . A simulated Mars atmosphere cabin with 10.3 mbar carbon dioxide level was created under HEPA filter vacuum at room temperature . The procedure to prevent muscle contraction by intramuscular injection of botulinum toxin produced a significant inhibition of neuronal carbonic anhydrase staining . The behaviors of bee venom mixtures containing different amounts of botulinum toxin and mellitin similar to carbonic anhydrase inhibitor analogs sulfonamides were investigated in vitro with a simulated Mars atmosphere. Later, the enzyme inhibition effect of these toxin mixtures was transformed into aerosol nano drops, and vaccine forms injected by air were created. Hematopoietic immunogen aerosol vaccine inhibited carcinogenic cells. The carcinogenic effect of the solar system's UV rays on astronauts traveling to Mars can be eliminated by aerosol vaccination of the aerosol carbonic anhydrase inhibitory toxin mixture formulation.
Day 2 full schedule
April 05, 2021 @ 15:30 - 17:35
Innovative adjuvant technologies for safe, potent & efficacious prophylactic and therapeutic vaccine for Humans
Dr. Prem Sagar
Innovative adjuvant technologies are the utmost need of the day for the vaccine industry to be able to produce safe, efficacious and potent vaccines against the varieties and complexities of the antigens. Conventional adjuvants used in human vaccines so far are not so efficient in tackling the challenge of the vaccine industry which requires a perfect balance between safety, efficacy and potency.
Seppic offers a range of innovative adjuvants dedicated for therapeutic and prophylactic human vaccines. In the area of therapeutic vaccine, MONTANIDE™ ISA 51 VG and MONTANIDE™ ISA 720 VG are the two novel adjuvants dedicated for human therapeutic vaccines. They have been used in more than 350 clinical trials involving cancer, AIDS, malaria or autoimmune disease vaccines and involving an accrual of more than 25000 patients. The adjuvants are rendering stable water-in-oil emulsions when mixed with water based antigenic media. Montanide ISA 51VG is based on a blend of mannide monooleate surfactant and mineral oil, whereas Montanide ISA 720VG uses a non mineral oil.
Therapeutic cancer vaccines are an interesting alternative approach to treat cancer by active immunotherapy. The use of highly purified antigens such as peptides are linked with weak and short-term immune responses. To improve it, Water-in-oil (W/O) emulsions such as MONTANIDE™ ISA 51 VG and Montanide ISA 720 VG represent an interesting option. Montanide™ ISA adjuvants interestingly enhance the immune response thanks to a depot effect at the injection site. It results in the strong activation of CD8+ and CD4+ cells and production of cytokines. Montanide™ ISA adjuvants are strong inducers of early high and long-lasting cell-mediated immune response. They are also widely used in clinical investigations and known as relatively safe. Also, MONTANIDE™ ISA 51 is already part of the CIMAVax-EGF vaccine, an NSCLC vaccine registered in 7 countries.
In the area of prophylactic vaccines, adjuvants play a key role in the vaccine formulation but are not easily accessible. Developing new, safe, and effective vaccines remains an issue for global health. As à concrete action, SEPPIC developed SEPIVAC SWE, the first oil in Water adjuvant in open access to all vaccine developers. O/W adjuvants are already used in several influenza vaccines and are known to be safe and effective in particular with elderly people. The use of this type of adjuvant technology in vaccine candidates against SARS-CoV-2 is part of the global research effort against COVID-19
SEPIVAC SWE™, was successfully tested in preclinical studies with various covid-19 antigens and showed an increased antibody and cell mediated responses. À dose sparing effect was also observed and can be an asset in the context of à global pandemic response.
Currently, SEPIVAC SWE is tested in humans in a COVID-19 vaccine candidate developed by The Vaccine and Infectious Disease Organization (VIDO), Canada.
Microencapsulation of Piscirickettsia salmonis antigens for fish oral immunization: Optimization and stability studies
Daniela Sotomayor GerdingDoctor
Universidad de La Frontera Chile
The development of fish oral vaccines is of great interest to the aquaculture industry due to the possibility of rapid vaccination of a large number of animals with reduced costs . Previously, we evaluated the effect of alginate-encapsulated Piscirickettsia salmonis antigens (AEPSA) incorporated in feed, effectively enhancing the immune response in Atlantic salmon (Salmo salar) . In this study, we seek to optimize microencapsulation efficiency (EE%) and to determine antigenic losses when facing these microparticles to different environmental conditions. AEPSA were produced by ionic gelation using an aerodynamically assisted jetting (AAJ) system and characterized (particle size and morphology) using a microscope. The Taguchi method was used to optimize antigen EE%. The effect of different environmental (pH, salinity and temperature) and gastrointestinal conditions on the microparticle stability were evaluated measuring the remaining protein content. The AAJ system proved to be effective to prepare AEPSA, microparticles with diameters between 7 and 45 μm were observed. The optimal conditions to obtain a high EE% determined by the Taguchi method were: medium flow rate (125 ml/h), high alginate concentration (3 % w/v), medium distance (20 cm) and medium pressure (1.25 bar). An EE% of 97.92% was obtained using the optimized conditions. Environmental conditions such as pH, salinity and temperature generated instability in the microparticles triggering protein release (Image). A 62.42% of the protein content was delivered at intestinal level after in vitro digestion. In conclusion, antigen alginate microparticles with a small particle size and high EE% can be effectively formed using an AAJ. Environmental conditions triggering protein release should be considered when using this type of system and adjust the doses of the bioactive according to the estimated losses. Future studies should seek to reduce these losses without affecting the release of the bioactive in digestion.
Huang Wei LingAcupuncturist
Medical Acupuncture and Pain Management Clinic
Since January 2020, Chinese scientists shared the SARS-CoV-2 genomic sequence and approximately, 321 research groups begin the search for vaccine since then. The CDC notes that immunocompromised patients may receive the vaccines so long as they have no contraindications to vaccination, but that they should be counseled about the unknown safety profiles of the vaccines in immunocompromised populations. Purpose; the purpose of this study is to demonstrate that the majority of the patients that the author is attending nowadays is in the category of immune compromised patients. Methods; the author did radiesthesia procedure to measure the energy of the seven chakra of 1000 patients during 2015 to 2020. Doing this measurement, the author was measuring the energy of the five massive organs in traditional Chinese medicine, responsible for the production of energy Yin, Yang, Qi and Blood, important to maintenance of health in the human body and the production of Zheng-Qi, that is responsible for the protection of the body against the invasion of external pathogenic factor, in this case SARS-CoV-2. Results; the result of this study is that more than 90 percent of the patients analyzed were in the lowest level of energy, meaning that their immune system are compromised because energy in TCM means immune system. Conclusion: to vaccinate people from COVID 19 nowadays, it is important to analyze the energy of each person before doing the vaccination because, according to the research made by the author, more than 90 percent of her population were in the lowest level of energy, meaning that they all have immune system very compromised.
Minhaz P Jawed H ShaikhResearcher
MET Institute of Pharmacy
The aim of present study is to formulate long acting lornoxicam depot microspheres using emulsion-solvent evaporation method and optimization of formulation by using design expert software. The main purpose of this study is to evaluate the effect of formulation variables (surfactant concentration, polymer type and concentration) on the preparation of lornoxicam loaded PLGA depot microspheres. Lornoxicam is used in treatment of Rheumatoid Arthritis which is condition where body’s immune system acts its own tissues including joints. Based on statistical data obtained, final optimization batch was formulated and evaluated. Evaluation parameter of microspheres are Particle size and Morphology, Drug content, % Encapsulation efficiency, differential scanning calorimetry, In-vitro release study, and Stability study. Scanning electron microscope image showed it has spherical shape with no drug crystal and porous on its surface without agglomeration. Differential scanning calorimetry and X-ray diffraction results suggested LXM was entrapped within the microspheres. Optimized batch was successfully prepared with particle size of 65.32 mm and EE of 77.45 %. In vitro drug release of optimized batch was show 75.98 % release up to 15days. Thus, from the obtained experimental results and statistical data it was shown that type of PLGA grade significantly affects the in vitro drug release from the microsphere that is as lactide content in PLGA increases the drug release from the microsphere will get decrease and as the concentration of polymer increases, the particle size of the microsphere will get increased. And also, as the surfactant concentration increases the entrapment efficiency of the microsphere will get decreased.
Vaccine and autoimmunity ;Why autoimmunity. Hyper-stimulation of the immune system. CP,SBI and vaccines as proofs of concept
Zabludowicz Center for Autoimmune Diseases
For over two decades now, plants have been explored for their potential to act as production platforms for biopharmaceuticals, such as vaccines and monoclonal antibodies. Without a doubt, the development of plant viruses as expression vectors for pharmaceutical production have played an integral role in the emergence of plants as inexpensive and facile systems for the generation of therapeutic proteins. More recently, plant viruses have been designed as non-toxic nanoparticles which can target a variety of cancers and thus empower the immune system to slow or even reverse tumor progression. The following presentation describes the employment of plant virus expression vectors for the treatment of some of the most challenging diseases known today. The presentation concludes with a projection of the multiple avenues by which virus nanoparticles could impact developing countries.
Multisystem Inflammatory Disease of childhood (MIS-C): An important complication of Pediatric COVID 19 Infection
Amrita DosanjhPediatric Pulmonologist
Childrens Hospital of Philadelphia and UCSD
The COVID 19 pandemic has been ongoing for more than one year. During the past year, there have been numerous studies focused on Pediatric COVID 19 and MIS-C. This presentation will summarize clinical features of the disease, review pediatric COVID 19 and studies which highlight the diagnosis. In addition, the differential diagnosis will be reviewed, and the distinguishing features highlighted. CDC statistics will be presented which update current knowledge of this disease in the U.S. Red flags which alert the Pediatrician to a possible case of MIS-C will be summarized during this presentation. The key laboratory biomarkers used to confirm the diagnosis of MIS-C and Kawasaki Disease will be discussed.
COVID-19 and Proinflammatory Immune responses: Lessons learned from infection with the Epstein-Barr Virus
Elias A. RahalAssociate professor
American University of Beirut (AUB)
Infection with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of the Coronavirus disease 2019 (COVID-19) pandemic, has been associated with dysregulated immune responses. Elevated levels of Th17 cells were detected in the peripheral blood of SARS-CoV-2 infected patients by some reports; Th17 cells are associated with proinflammatory responses, with asthma as well as with autoimmune diseases such as rheumatoid arthritis. The increase in Th17 cells in COVID-19 patients may indicate that such an immune response plays a significant role in the severe inflammation seen in the disease. We have previously reported a correlation between the Epstein Barr virus and the Th17 response in animal models as well as in rheumatoid arthritis patients. Are similar responses occurring in COVID-19 patients and would targeting the Th17 axis be of relevance in the management of the disease?
Huang Wei LingAcupuncturist
Medical Acupuncture And Pain Management Clinic
Diabetes Mellitus (DM) is a metabolic disease, involving inappropriately elevated blood glucose levels. Cancer is characterized by uncontrolled cell growth and acquisition of metastatic properties. In traditional Chinese medicine, diabetes is considered Yin deficiency and Heat retention. Cancer is formed by energies deficiencies and Heat retention. Purpose: the purpose of this study is to demonstrate that diabetes and cancer came from the same root that are the energies deficiencies and formation of internal Heat in the chakras energies centers leading to different manifestations on the leaf level. Methods: though two cases report of patients who have diabetes and also develop cancer latter. Both patients have chakras’ energies deficiencies from one to six, all rated in one. It was used to treat them Chinese dietary counseling, auricular acupuncture with apex ear bloodletting and chakras’ energies replenishment using homeopathies according to the theory Constitutional Homeopathy of the Five Elements based on Traditional Chinese Medicine and crystal-based medications. Results: The result of this study was that both patients improved from their glycaemia using the tools and also the female patient cured her thyroid cancer only using these methods of treatment. Conclusion: patients with diabetes and cancer have chakras ‘energies centers in the weakest level of energy as the root and the corrections of this energies imbalances using homeopathy medications, Chinese dietary counseling and auricular acupuncture wit apex era bloodletting were important to recover from both diseases at the same time.