Vaccines R&D & Vaccination

Jeanne Moldenhauer, Vice-President of Excellent Pharma Consulting has more than 30 years’ experience in the pharmaceutical industry. She chaired the Environmental Monitoring/Microbiology Interest Group of PDA for more than 15 years, served on the Scientific Advisory Board of PDA for 20 years, founded the Rapid Microbiology User’s Group™, and is a Member of ASQ and RAPS. She is the author of many books and numerous publications (book chapters and magazine articles)

In this every changing world of regulatory expectations, developing a regulatory strategy for environmental control can be challenging. It will describe the various components of the program, how the components interrelated, and what the requirements are for each component.  Additionally, it will discuss the various regulatory requirements for this type of monitoring.  Lessons learned and typical regulatory observations for these types of systems will also be discussed.  Lastly, discussion will be conducted on the various methods available for automation of these systems.  This discussion includes the type of reports and trending expected for the program.

Dr. Ruan is the Sr. Director of process development and production at Emergent Biosolutions (USA). She has extensive experience in bioprocess development from preclinical to licensure.  She has a Ph.D. degree in biochemical engineering from South China University of Science and Technology. She managed Process development, clinical production (Phase I, Phase II, and Phase III), facilities, materials management, validation, Tech Transfer and CMO.  Dr. Ruan is responsible for developing and manufacturing oral delivery vectors and injectable virus-like-particles for vaccines, as well as researching, evaluating, and optimizing new technology platforms to improve the production scale and stability of the products.

Dr. Ruan is the Sr. Director of process development and production at Emergent Biosolutions (USA). She has extensive experience in bioprocess development from preclinical to licensure.  She has a Ph.D. degree in biochemical engineering from South China University of Science and Technology. She managed Process development, clinical production (Phase I, Phase II, and Phase III), facilities, materials management, validation, Tech Transfer and CMO.  Dr. Ruan is responsible for developing and manufacturing oral delivery vectors and injectable virus-like-particles for vaccines, as well as researching, evaluating, and optimizing new technology platforms to improve the production scale and stability of the products.

Brian G Hubka is the CEO of Contamination Prevention Technologies, Inc.  This company provides a vast array of contamination remediation and prevention technologies and products to eliminate and prevent mold, bacteria, viruses, prions and the like. They are also specialists in biofilm remediation and elimination. He also consults on contamination issues in pharmaceutical and biotechnology companies. He has worked with Pfizer, Amgen, Celgene and many others. He is a Graduate of University of Notre Dame pre-medicine.  He is also a frequent speaker and has authored book chapters for many PDA/DHI books.

Contamination Prevention is a common occurrence costing time delays for product release, product rejection by quality and product recall by the FDA. There are several new technologies that can quickly and completely eliminate contamination: How to prevent certain types of contamination. Identify extremely effective disinfectants that don’t harm stainless steel. Identify easier methods to validate cleaning and disinfection using biological indicators. Preventing and eliminating biofilm with ambient water.

Ayoub A Bazzaz has completed his PhD from Nottingham University, UK and continued Postdoctoral research works for over 10 years at Leeds, Liverpool and Cardiff Universities in UK. He is one of the Founder of Faculty of Medicine of Tikrit University, Iraq and first head of Anatomy Department 1988-1991. He has supervised and refereed many PhD and MSc students in Iraq, KSA, Libya and UK and has over 60 published scientific papers in reputed International journals.

The study involved a general survey of six diagnosed common parasitic infectious disease, amoebiasis, beaver fever (giardiasis), oriental spot (leishmaniasis), black fever (Kala azar), hydated disease (cystosis) and toxoplasmosis, for outpatients attended a few different state hospitals, Al-Jumhuri, Azadi and Children hospitals for the years 2009-2017. The amoebiasis involved infection with Entamoeba histolytica had the highest records (80%) amongst other five parasites in year 2011, followed by giardiasis (18%) in 2012, respectively. The annual peak of total infection for all these six parasites was in year 2011 followed by years, 2013, respectively. The highest monthly records of general infection were in June followed by July and October, respectively. The present work provides a national survey of general parasitic infection prevalence in a few Iraqi cities. Similar surveys to cover other cities would complimentary be beneficial to promote to an official level which imply a wider idea of the prevalence of these parasites in the country. Future works should involve medical treatments, i.e. vaccination to siege the prevalence of these intestinal and coetaneous diseases.

Prince Sharma (56) completed his PhD at the age of 25 years and is currently Professor of Microbiology working in the areas of Reverse Vaccinology, Industrial Enzymes and Biosensors for diagnostics. He has one patent granted and two technologies transferred to industries (Cadilla, India and NEB,USA). Published 95 papers, completed 12 research projects, guided 22 PhD students.  Got Glaxo Smith Kline Vaccine Travel Award to present work on Reverse Vaccinology in ECCMID conference (2016) in Amsterdam. Defence Threat Reduction Agency, USA, sponsored him for European Biosafety Association Conference in Madrid, 2017. He is Associate Editor of Indian Journal of Microbiology and is Fellow of the Academy of Microbiological Sciences

Acinetobacter baumannii has emerged as a multi drug resistant opportunistic human pathogen causing serious nosocomial infections in immunocompromised patients. Recently, WHO has released a list of antibiotic resistant priority pathogens and mentioned A. baumannii as the critically most dangerous one. Emergence of resistant strains worldwide is a serious concern and novel approaches like vaccination could become effective in preventing A. baumannii infections.

In our lab, the pan-proteome of A. baumannii was analysed in silico to find potential vaccine candidate proteins on the basis of sub-cellular localization, number of transmembrane helices, adhesion probability, ability to bind MHCs and dissimilarity with human and mouse proteome. Out of 4589 proteins, 51 including pilus assembly proteins, competence proteins, siderophore receptor proteins, FilF, NucAb, BamA, peptidase, efflux proteins and autotransporter proteins fulfilled the criteria of good vaccine candidates. Three proteins viz. FilF, BamA and nuclease were cloned in pET28-a, expressed in E.coli BL21 (DE3) and purified. Their immunoprotective efficacies were evaluated in A. baumannii associated murine pneumonia models (intratracheal and intranasal) developed in our lab. Immunization with purified recombinant proteins evoked significant antibody titers in mouse that facilitated the reduction of bacterial load in lungs by several log cycles (2,2 by FilF immunization, 2,3 by BamA and 4,5 by nuclease 12 h and 24 h post infection respectively). Levels of pro-inflammatory TNF-α, IFN-γ, IL-1β and IL-6 cytokines were reduced and those of anti-inflammatory IL10 increased significantly. Decreased neutrophil infiltration was observed in immunized mice. Active immunization with NucAb, FilF and BamA resulted in 20, 50 and 80% survival of A. baumannii challenged mice, whereas passive immunization with NucAb and BamA resulted in 40 and 60% survival. FilF, BamA and NucAb, predicted as potential vaccine candidates by in silico analysis, showed immunoprotective efficacy and can contribute significantly in vaccine development against A. baumannii.

Cheepsattayakorn has graduated Doctor of Medicine from Chiang Mai Medical School, Chiang Mai University, Chiang Mai, Thailand in 1986. He then further had trained in Internal Medicine, Pulmonology, and Radiology at Chiang Mai University Medical School. He has graduated numerous Fellowships in Respiratory Medicine from the Royal Colleges of Physicians of London, Edinburgh and Thailand, Royal College of Physicians and Surgeons of Glasgow, American College of Physicians, and American College of Chest Physicians. Presently, he serves both Editor and Editorial Board Member and also Referee of several international journals. He has very high experience in the fields of Pulmonary Diseases and Tuberculosis including Infectious Diseases and Immunology. He has numerous scientific publications, more than 130 publications both in national and international journals and books. His research interests include novel therapeutics in lung cancer; non-tuberculous mycobacterial infection in HIV- infected patients; multidrug resistant tuberculosis patterns in HIV- infected patients; chemokine gene polymorphisms and their susceptibility to tuberculosis; breath tests in respiratory and critical care medicine; tropical infectious diseases; human genetics and infectious diseases and environmental and occupational pulmonary diseases.

 

Zika virus (ZIKV) remains an public health challenge with requisition of intensive action although the recent declaration of Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) Director-General on November 18, 2016. With possible continuation of the outbreaks, the WHO/UNICEF have established Zika Virus Vaccine Target Product Profile (TPP) as a strategy to fight against Zika virus infection and disease, particularly prenatal Zika virus infection accompanying with the WHO Zika Strategic Response plan. WHO SAGE would advise at least two scenarios of the immunization strategies: 1. Outbreak response and 2. Routine or endemic transmission use. The City College of New York and a drug company in New York City conducted a Zika virus vaccine against the mosquito-borne Zika virus focusing on virus-like particle (VLP) in animal models and demonstrated the preclinical results with favorable outcomes. The studied VLP vaccine formulations tested in animals can elicit the protective antibodies with neutralizing activity higher than or equivalent to the activity present in recovered Zika-virus-infection patient’ s serum with good tolerance and good safety. The National Institute of Allergy and Infectious Diseases (NIAID) is developing a vaccine, called “ AGS-v ” which designed to protect against multiple mosquito-borne diseases, including Zika virus infection. AGS-v candidate with being evaluated in a Phase I clinical trial at the National Institute of Health (NIH) Clinical Center in Bethesda, Maryland, triggers an immune response to mosquito salivary proteins from mosquito salivary gland. NIAID is also developing several other Zika virus vaccine candidates, such as a live-attenuated investigational vaccine designed to protect against Zika virus infection and dengue virus infection, which is closely related to a dengue vaccine candidate presently being evaluated in a large Phase III study in Brazil. A monovalent vaccine candidate which is designed to protect only against Zika virus will enter a Phase I trial at University of Vermont and Johns Hopkins University in Baltimore. An investigational Zika vaccine which uses a genetically engineered version of vesicular stomatitis virus, an animal virus that primarily affects cattle (VSV) was successfully used in an investigational Ebola vaccine developed by NIAID. This VSV vaccine candidate is underway to evaluate the vaccine candidate in tissue culture and animal models. NIAID is co-funding the Phase I clinical trials program with the Walter Reed Army Institute of Research (WRAIR), serving as the regulatory sponsor for several of these clinical trials and providing other support in developing a purified inactivated Zika vaccine, called “ ZPIV ”. Four of five Phase I trials for ZPIV testing have launched at the WRAIR Clinical Trial Center in Silver Spring, Maryland, clinical research center “CAIMED” (part of Ponce Health Sciences University in Puerto Rico), the Center for Virology and Vaccine Research (part of Beth Israel Deaconess Medical Center and Harvard Medical School in Boston), and the Center for Vaccine Development at the Saint Louis University School of Medicine. A Deoxyribonucleic Acid (DNA)-based Zika vaccine candidate developed at NIAID’s Vaccine Research Center (VRC) is similar to the VRC’s investigational flavivirus vaccine for West Nile virus infection. This vaccine candidate entered a Phase I clinical trial at NIAID in August 2016. A second Phase I trial and a Phase II clinical trial were launched in December 2016 and March 2017, respectively. Sites of a Phase II clinical trial included Houston, Peru, Puerto Rico, Costa Rica, Brazil, Mexico and Panama. This two-part trial, called “VRC 705”, will further evaluate the immunogenicity and safety of this vaccine candidate. NIAID‘s VRC is collaborating with the University of Pennsylvania and the two drug companies to evaluate several investigational messenger-Ribonucleic Acid (mRNA) vaccine candidates ( a gene-based platform similar to DNA vaccine candidates). An investigational mRNA vaccine candidate is being evaluated in a Phase I trial, whereas another vaccine candidate could be entered clinical trials in late 2017. A previous study on a live-attenuated Zika virus vaccine candidate in mouse model revealed that a live-attenuated Zika virus vaccine candidate containing a 10-nucleoside deletion in the 3ʹ translated region of the Zika virus genome (10-del ZIKV) can be highly attenuated, immunogenic, and protective in type 1 interferon receptor-deficient A129 mice. This attenuated 10-del ZIKV was incapable of infecting mosquitoes after oral feeding of spiked blood meals, representing an additional safety property. Two recent studies reported the successful experimental ZIKV vaccine candidates testing in animal models, one by Richner et al and another by Pardi et al. Both vaccine candidates were engineered at the mRNAs with sequences encoding the ZIKV precursor membrane (prM) glycoprotein and envelop (E) glycoprotein, which is critical to viral attachment, entry, and replication in the infected host cells.  In conclusion, it is currently still unclear about the role of potentially cross-reactive antibodies in disease enhancement or prevention. Although several in vitro studies have revealed both potentially cross-reactive antibodies in disease enhancement or prevention, the generalization of these studies to the clinical relevance and human immunological experience is impossible. Preliminary data in flavivirus primed non-human primates do not demonstrate any features of enhanced disease. However, it is critical area for further field evaluation.