Day 1 :
Keynote Forum
Helder Fernando BrÃgido Martins
Retired Senior Manager at WHO, Mozambique
Keynote: Bringing to widespread public use latest technologies and innovations in vaccines and immunization: A point of view from a developing country – Mozambique
Time : 10:00-11:00
Biography:
Abstract:
Despite the generalized consensus that most effective technologies are useless if not widely used, between the discovery of the various effective vaccines and their widespread use it has always elapsed a long time. In the past, among others, two main factors have justified this long gap of time: widespread use of vaccines implies a complex managerial and logistic delivery system and the introduction of new vaccines imply costs. Money is not always available, particularly in developing countries. In 1974, the EPI programme approved by WHO and recommended to be implemented all over the world, was a gigantic step forward to create the managerial and logistic system to deliver vaccines. At same time, a new era of vaccine promotion started, to raise conscience of vaccines as one of the most cost/effective measures in Public Health. However, even after the EPI was widely adopted all over the world, there has been always a considerable period, between the discovery of new vaccines and their introduction in EPI national programmes. In recent years, a lot of progress had been made in vaccine research and development and a great number of new vaccines were approved for public use and some are still on the pipeline. However, the time between the approval of a vaccine for public use and its effective widespread use is still much more than the desirable and there still are a lot of underutilized vaccines. To complicate the situation, in the last 10 to 20 years, an unexplainable anti-vaccine lobby has been very active, involving many Medical Doctors, to discourage the general public to use vaccines. On the other side, the paradigm of the original EPI programme was based on vaccines for children and women in the fertile age. This was understandable, because, at the time, the important task was to address priority problems. In the last 20 to 30 years, the conscience of the health professionals has moved to realize that there are also very useful and effective vaccines for teenagers, elderly people and adults that should not remain underutilized. Consequently, the EPI paradigm has changed, to include a much bigger number of vaccines. With well-established EPI Programmes, in almost all countries of the world, the managerial and logistic delivery system problems are solved (or, at least, they are not very constringent any more) and the financial constraints to bring to widespread public use an increasing number of vaccines became the main issue, but not the only one. Therefore, now a day, the great challenge is how to reduce the time gap between the approval of a vaccine for public use and its effective widespread use. In this paper, the author uses his wide technical and managerial skills and experience to present suggestion on how to minimize this problem.
Keynote Forum
Nicholas Jackson
Sanofi Pasteur, Lyon, France
Keynote: RSV prevention for high-risk populations: Different approaches for different age groups
Time : 11:30-12:30
Biography:
Abstract:
Respiratory syncytial virus (RSV) represents an important cause of lower respiratory tract illness in infants and children and can result in long-term impacts on respiratory health. RSV also represents a major viral cause of acute exacerbations in chronic obstructive pulmonary disease in older adults. Based on the Immunobiology of RSV, different approaches are necessary to prevent and reduce the burden of disease caused by RSV in different age groups. This presentation will provide an overview and status of the RSV vaccine field (active and passive approaches), as well as a more detailed view of the Sanofi Pasteur efforts in targeting RSV-vulnerable populations.
Keynote Forum
Stefania Di Marco
ADVENT - IRBM Science Park SpA, Italy
Keynote: Production and characterization of viral vectors for vaccine development
Time : 13:30-14:30
Biography:
Stefania Di Marco is a PhD Biochemist with 18-year research experience in preclinical drug discovery and development, employing molecular biology, biochemistry and X-ray crystallography for functional studies and structure-based drug design in the pharma industry. Eight-year GMP experience in production, testing and release of investigational vaccines for infectious diseases and cancer. She is an author of 54 publications and inventor of four patents (h-index 31; source Google Scholar). Currently, Qualified Person at the GMP facility ADVENT, c/o IRBM Science Park, Pomezia-Roma.
Abstract:
Potent immunogenicity and lack of prolonged transgene expression have made Adenoviruses (Ad) attractive viral vectors for vaccine development. They possess a stable virion, allowing inserts of large foreign genes, they can infect many different cell types and the transferred information remains epichromosomal, thus avoiding the risk of insertional mutagenesis. Preclinical and clinical results conclusively showed superiority of Adenovirus-vectored genetic vaccines, based on the most common human Adenovirus serotype 5 (Ad5), for the induction of T cell response. However, pre-existing immunity to Ad5 has shown to blunt significantly the immunological response induced by Ad5-vectored vaccines in rodents, non-human primates and in humans. Chimpanzee Adenoviruses (ChAd) do not cause pathological illness in humans and antibodies against them have low/no seroprevalence in the human population. Moreover, they have been shown to be very good immunogens in animal models. A large screening of ChAd has been performed and several strains were identified, which were rendered replication incompetent and suitable as vaccine vector candidates. Amongst this collection, several replication defective chimpanzee-derived adenoviruses have been selected for evaluation as clinical products against infectious diseases like Ebola, HCV, RSV, leishmaniosis and malaria. The production and the characterization of the ChAd platform and their development as prophylactic and therapeutic vaccines will be presented.
Keynote Forum
Liwei He
Sanofi Pasteur, Canada
Keynote: Flow cytometry: An efficient method for antigenicity measurement and particle characterization on an adjuvanted vaccine candidate H4-IC31 for Tuberculosis
Time : 10:00-11:00
Biography:
Liwei He has over 25 years of experience in academia and pharmaceutical industry. Currently he is working as a Scientist in the Analytical Research and Development Department at Sanofi Pasteur in Toronto. He has contributed to several vaccine projects and developed analytical test methods for characterization of vaccine products. He has also led several new multiplex based approaches for characterization and quantification of antigens and has contributed to the validation of these methods in accordance with the regulatory guidelines. To date, he has contributed to several scientific publications and co-authored a few patents related to vaccine technologies.
Abstract:
We have developed an accurate, precise and stability-indicating flow cytometry (FC) based assay to directly measure antigenicity of H4 protein in a vaccine formulation of H4-IC31, without desorbing the H4 protein from the IC31 adjuvant. This method involves immuno-staining of H4-IC31 complex with anti-H4 monoclonal antibodies (mAbs) followed by FC analysis. The assay is not only able to consistently measure H4 antigenicity levels in H4-IC31 stored under normal condition at 2-8°C, but also able to detect changes in H4 antigenicity after H4-IC31 undergoes heat stress or freeze-thawing. In addition, the FC method is able to characterize particle morphology while measuring antigenicity. The biological relevance of the changes in H4 antigenicity detected by the FC assay was supported by an in vitro cell based functional assay using human PBMCs to measure IFN-gamma (IFN-γ) secretion upon re-stimulation with H4-IC31. Our results show that the FC based antigenicity assay can efficiently monitor the biological and physicochemical properties of H4-IC31 and is an indicator for adjuvanted vaccine product stability.
- Vaccines | Vaccines against Infectious Diseases | Current Research & Future Challenges | Pediatric Vaccination | Cancer, Malaria & TB Vaccines | Travel & Edible Vaccines | Vaccines & Autism | Vaccines for Pregnant Women & Neonates | Vaccine Production & Development
Chair
Helder Fernando BrÃgido MARTINS
Retired Senior Manager at WHO, Mozambique
Session Introduction
Liwei He
Sanofi Pasteur, Canada
Title: Flow cytometry: An efficient method for antigenicity measurement and particle characterization on an adjuvanted vaccine candidate H4-IC31 for Tuberculosis
Time : 14:30-15:00
Biography:
Abstract:
Ashish Sahai
Serum Institute of India Pvt. Ltd, India
Title: Development of new purified vero cell rabies vaccine (Rabivax-S) at the Serum Institute of India Pvt.Ltd.
Time : 15:00-15:30
Biography:
Ashish Sahai has over 29 years of rich experience in the Biotechnological industry and Research Institute. He has experience in Research and Development, Quality Control, Quality Assurance, Production of Vaccines. He has acquired experience in protein purification, molecular sieve chromatography, ion exchange chromatography, electrophoresis, affinity chromatography, polymerase chain reaction, hybridoma technology. He has specialization in downstream processing of viruses using affinity chromatography.
Abstract:
Introduction: Rabies is a 100% vaccine-preventable disease. Rabies disease still causes human deaths in the endemic areas in Asia and Africa. A cheap, rabies vaccine for humans that could be used in mass vaccination campaigns would be a valuable weapon against rabies. Serum institute of India Pvt. Ltd. has developed a new purified vero cell inactivated and lyophilized rabies vaccine (Rabivax-S) which is now a WHO prequalified rabies vaccine.
Methodology, Theoretical Orientation & Findings: Large scale production of Vero ATCC CCL81 cells were seeded in cell cube system. Then cells are infected with Pitman Moore (PM 3218) strain of rabies virus. After 48-72 hrs, infected cells are washed. The multiple harvests are collected from one cell cube system and clarified by filtration. Clarified harvest is concentrated using tangential flow filtration system. Inactivation of rabies virus is done using beta-propiolactone (BPL). Next step of purification is done by affinity column chromatography in order to remove BSA and host cell DNA and diafiltration to remove high salt concentration. Purified rabies antigen is prepared by adding stabilizer to diafiltered antigen and finally filtered by 0.22 micron filtration and stored in ethyl vinyl acetate bags. A number of purified rabies antigen bags are blended to achieve set antigen content in final bulk. The liquid vaccine is filled in 1 ml USP type 1 clear and tubular vial and lyophilized. With the lyophilized vial of rabies vaccine 1.0 ml of sterile water for injection is supplied as a diluents.
Conclusion & Significance: Study gives well developed new purified vero cell rabies vaccine (Rabivax-S), following all the GMP requirements. Animal study has demonstrated no toxicity issue. We evaluated its safety, toxicity and immunogenicity in post-exposure prophylaxis in clinical trials by IM and ID routes. This vaccine is good option among the available modern WHO prequalified rabies vaccine. Filling, lyophilization and packaging of final product.
Yongliang Feng
Shanxi Medical University, China
Title: Long-term immune effects of different vaccination regimens for hepatitis B vaccine among patients receiving methadone maintenance treatment: Secondary analysis of a randomized clinical trial
Time : 15:45-16:15
Biography:
Yongliang Feng is an Associate Professor of Epidemiology from Shanxi Medical University, Taiyuan, China. He has been working in the field of epidemiology since 2005. He has been the Principal Investigator for 1 grants from the National Natural Science Foundation of China (NSFC), and 5 projects from the Ministry of Science and Technology, Shanxi Provincial Foundation and Shanxi Medical University. His research mainly focuses on the immunogenicity and safety of hepatitis B vaccine among people at high risk for HBV infection. His research also focuses on investigating the environmental and genetic factors on risk of mother-baby infection of hepatitis B virus and its immunological profile as well as its mechanism. He has published more than 50 research papers in academic periodicals at home and aboard, and wrote or participated in compiling 4 treatises and textbooks.
Abstract:
Objective: To explore the long-term immune effects of different vaccination regimens for hepatitis B vaccine in methadone maintenance treatment patients.
Methods: The randomized, double-blinded, parallel-controlled trial (receiving three intramuscular injections of 20 μg or 60 μg recombinant hepatitis B vaccine at months 0, 1, and 6, respectively, Abbreviated as IM20 × 3 or IM60 × 3) in MMT patients was conducted from September 2014 to December 2015 at first trial stage. At secondary trial stage, we compared the long-term immune effects of different vaccination regimens during 3-year follow-up extended to September 2018 in 144 MMT patients who were tested at months 7.
Results: The long-term immune effects on different follow-up times of IM20 × 3 and IM60 × 3 regimen of recombinant hepatitis B vaccine were: GMC of anti-HBs, positive conversion rate, hyper-response rate: (630.400 mIU/mL vs. 742.900 mIU/mL), (80.82%, 59/73 vs. 87.32%, 62/71), (42.47%, 31/73 vs. 56.34%, 40/71) at months 7; (405.600 mIU/mL vs. 331.300 mIU/mL), (61.97%, 44/71 vs. 67.74%, 42/62), (23.94%, 17/71 vs. 30.65%, 19/62) at months 18; (218.500 mIU/mL vs. 291.500 mIU/mL), (56.41%, 22/39 vs. 62.86%, 22/35), (15.38%, 6/39 vs. 28.57%, 10/35) at months 30; (71.040 mIU/mL vs. 100.300 mIU/mL), (52.78%, 19/36 vs. 65.52%, 19/29), (16.67%, 6/36 vs. 24.14%, 7/29) at months 42. There was no significant difference at different follow-up times (P>0.05).
Conclusion: The three 60 μg hepatitis B vaccination yield a similar long-term immune effects compared to the 20 μg vaccination.
Suping Wang
Shanxi Medical University, China
Title: TLR3 signaling pathway on the effect of PBMC recombinant HBsAg immune response in vitro study
Time : 16:15-16:45
Biography:
Suping Wang is a Professor of Epidemiology from Shanxi Medical University. She has been working in the field of epidemiology since 1983. She has been the Principal Investigator for 5 grants from the National Natural Science Foundation of China (NSFC), and about 20 projects from the Ministry of Science and Technology, the Ministry of Education and Shanxi Provincial Foundation. Her research mainly focuses on investigating the environmental and genetic factors on risk of mother-baby infection of hepatitis B virus and its immunological profile as well as its mechanism. Her research also aims at studying on the relationship between the environmental and genetic factors and adverse birth outcomes. She has published more than 100 research papers in reputed journals, and wrote or participated in compiling more than 10 treatises and textbooks.
Abstract:
Objective: To investigate the effect of on the PBMC recombinant HBsAg immune response in vitro.
Methods: PBMC were divided into 3 groups: blank group, TLR3 activator group (treated with polyI:C) and TLR3 inhibitor group (treated with TLR3 inhibitor), and cultured for 48h. TLR3 signaling pathway molecules in the collected cells were detected by Flow Cytometry, and TLR3/TRIF mRNA and HBV DNA in PBMC by quantitative real-time PCR. Then all the 3 groups were treated with recombinant HBsAg and cultured for 72h, and immune cells were detected by Flow Cytometry.
Results: The percentage of TLR3 (19.21%), pNF-κBp65 (13.73%), pIRF3 positive cells in PBMC (12.64%) among polyI:C group were significantly higher than those in blank group (11.54%, 8.72%, 9.71%, respectively) (P<0.05). The percentage of TLR3 (8.56%) and TRIF (89.61%), NF-κBp65 (89.22%) and IRF3 (91.62%) positive cells in TLR3 inhibitor group were slightly lower than blank group (11.54%, 89.64%, 90.97%, 92.99%, respectively). The expression level of TLR3 (8.98×103) and NF-κBp65 (2.62×104) in polyI:C group were significantly higher than that in blank group (8.09×103 and 2.23×104) (P<0.05). The expression of TLR3 in inhibitor group (7.54×103) was lower than blank group (P=0.045). After PBMC treated with rHBsAg, the proportion of B cells in lymphocytes (5.31%) and plasma cells in B cells (67.71%) among polyI:C group were higher than blank group (4.23% and 58.82%) (P<0.05). The proportions of mDC (4.12%) and pDC (2.96%) in PBMC were also increased compared with blank group (2.51% and 1.73%).
Conclusion: The increased expression of TLR3 protein and activation of NF-κB and IRF3 may promote the maturation of B cells and DC cells, which play an antigen-presenting role and promote formation of plasma cells, and then improve the potential of expression of anti-HBs to enhance the immune response to rHBsAg.