Tumor liberated protein (TLP) has been previously described as a TAA (complex) present in the sera from lung cancer patients with early stage disease. Since early detection improves overall survival in lung cancer, identification of screening biomarkers for patients at risk for the development of this disease represents an important target. Starting from the peptide epitope RTNKEASI previously isolated from TLP complexes, we generated a rabbit anti-RTNKEASI serum. This antiserum detected and immunoprecipitated a 55kDa protein band in the lysate of the lung cancer cell line A549. This protein band was identified as aldehyde dehydrogenase isoform 1A1 through mass spectrometry, revealing the molecular nature of at least one component of the previously described TLP complex. Next, we screened a cohort of 29 lung cancer patients (all histologies), 17 patients with non-neoplastic lung pathologies and 9 healthy donors for the presence of serum ALDH1A1 and global serum ALDH by enzyme-linked immunosorbent assay. This analysis indicated that the presence of ALDH was highly restricted to patients with lung cancer. Interestingly, the global ALDH test detected more lung cancer patients compared to the ALDH1A1-specific test, suggesting that other ALDH isoforms might add to the sensitivity of the assay. Our data suggest that ALDH levels may therefore be evaluated as part of a marker panel for lung cancer screening. Finally, the ability of the immune system to recognize a TAA, enables the development of a vaccine approach for preventive and therapeutic application and represents a main target of this field of research.
Giulio Tarro graduated from Medicine School, Naples University (1962). Research Associate, Division of Virology and Cancer Research, Children’s Hospital (1965-1968), Assistant Professor of Research Pediatrics, College Medicine (1968-1969), Cincinnati University, Ohio. Oncological Virology Professor, Naples University (1972-1985). Chief Division Virology (1973-2003), Head Department Diagnostic Laboratories, (2003-2006). D. Cotugno Hospital for Infectious Diseases, Naples; Emeritus, 2006 -. Since 2007 Chairman Committee of Biotechnologies and VirusSphere, World Academy Biomedical Technologies, UNESCO, Adjunct Professor Department Biology, Temple University, College of Science and Technology, Philadelphia, recipient of the Sbarro Health Research Organization lifetime achievement award (2010). His researches have been concerned with the characterization of specific virus-induced tumour antigens, which were the "finger-prints" left behind in human cancer. Achievements include patents in field; discovery of Respiratory Syncytial Virus in infant deaths in Naples and of tumor liberated protein as a tumor associated antigen, 55 kilodalton protein overexpressed in lung tumors and other epithelial adenocarcinomas.
Innovation and technology have been and continues to be key enablers to develop and manufacture vaccines. This has resulted in a significant increase of vaccines on the markets with increased quality and safety attributes. In addition, the pharmaceutical industry has seen a significant shift from small molecules to biologicals. This presentation will review the evolution of vaccine development and manufacture and the role of innovation and technology. As competition and cost increases, a number of strategies to leverage innovation and technology for rapid product development to shorten time to clinical trials and increasing productivity are discussed. Specific examples of accelerating process and analytical development will be provided. In addition, how we continue the evolution of vaccine development and manufacturing in the future.
Tony D' Amore Obtained Ph.D. in Biochemistry from the University of Windsor and MBA from Wilfred Laurier University. Joined sanofi pasteur in 1994 (then Connaught Laboratories) as a Purification Scientist. He has taken on successive leadership positions, including the Head of Bioprocess Research and Development North America at Sanofi Pasteur, responsible for process development and the manufacture of clinical trial material. In 2015 he was appointed Global Vice President of Product Research & Development, responsible for process and analytical development, the manufacture of clinical trial material and the delivery of clinical supplies to the clinical trial sites.
Vaccines are valuable and important medicinal products which require a specific supply chain. In many countries in the developing world this supply chain is broken, vaccines are not where they are needed or are not active anymore. Therefore it is very important to achieve vaccine visibility and traceability from manufacturer to patient, securing that safe vaccines are delivered to the right place, in the right quantities, at the right time to all children and adults who need them. WHO has started to recommend barcoding as a tool to ensure traceability already years ago, GAVI and UNICEF are now also asking their suppliers to use global standards for unique identification of vaccines. This will enable Track and Trace of vaccines and therefore contribute to patient safety, supply chain efficiencies and the overall goal of increasing immunization coverage to support universal health coverage. The presentation will provide background and details of global standards for traceability.
Ulrike Kreysa is responsible for the Healthcare sector at the GS1 Global Office in Brussels and works with her local colleagues in 114 countries across the world to develop and implement GS1 standards in the healthcare industry. Having started her career as a Pharmacist as well in public pharmacies as in a large German university hospital she manages GS1 Healthcare, the global GS1 user group, formed by the stakeholders in the healthcare supply chain, including pharmaceutical and medical device manufacturer, wholesaler/distributor, group purchasing organizations, hospitals, pharmacies, logistic providers, governmental and regulatory bodies and associations. GS1 Healthcare has the mission to lead the Healthcare sector to the successful development and implementation of global standards. Worldwide patient safety and supply chain efficiencies will be enhanced globally through standards for AIDC (Automatic Identification and Data Capture), global data synchronisation and traceability. Ulrike works regularly with decision makers from leading companies and regulatory bodies like US FDA, Chinese NMPA, EU Commission and many others to drive harmonisation of standards in the implementation across the world. She has facilitated the WHO Vaccines barcode subgroup as well as the RH GTAG (RH Global Traceability Advisory Group), which developed worldwide guidance for the automatic identification with barcodes to enable traceability and an improved supply chain.
Clostridium perfringens is an anaerobic spore-forming, pathogenic bacterium that is responsible for severe diseases in humans and livestock. In the present study, an epsilon-beta fusion toxin was expressed as a soluble protein in E. coli and the recombinant cell lysate was used for immunization studies in mouse. Potency of the toxin (as an antigen) induced 6 and 10 IU/ml of epsilon and beta anti-toxin in rabbit, respectively. These titers were higher than the minimum level required by the European Pharmacopoeia for epsilon and beta toxins. Experimental challenge with the recombinant fusion toxoid revealed that it could protect mice against C. perfringens epsilon and beta toxins. Toxicity of the fusion toxin was studied by histopathological findings, which were the same as the native toxins. In conclusion, E. coli is a suitable expression host for immunogenic epsilon-beta fusion toxin of C. perfringens.
Dr. Reza Pilehchian has more than 30 years experience in the field of veterinary anaerobic vaccine research and production at Razi vaccine and serum research institute, Alborz. Iran. He is fully expert in the field of GLP, GCP, GMP, Biologicals manufacturing, pharmaceuticals and medical devices consultancy. Now Dr. Pilehchian is working as CEO of Behafza GMP consulting company. Behafza company duty is to to bring information for minimum requirements of the Biological and Pharmaceutical product manufacturing to the related companies. the company present consultancy and bilateral logical and efficient correlation to ensure them that the standards are correctly applied and implemented so healthy, efficient and potent products are marketed.
The lumen of the gastrointestinal (GI) tract is a complex ecosystem where an enormous quantity of different bacterial species, termed the microbiota, establishes a generally symbiotic relationship with host immune system and epithelial cells. It has been shown that certain pathogens, including dengue virus (DENV) may cause dysfunction of the GI tract leading to microbial translocation (MT). The correct interaction of the components of the GI tract permits the normal function of this ecosystem, reduces the risk of an excess of MT from the lumen of GI tract to the systemic circulation, and prevents its systemic consequences such as immune activation. Officially, the definition of MT includes the passage of both viable and nonviable microbes and microbial products such as lipopolysaccharide (LPS) across an anatomically intact intestinal barrier. We have shown that there is an association between severity of dengue and MT. Results of several studies will be presented and the role of LPS in pathogenesis will be discussed.
Dr Martina studied Biomedical Sciences and graduated as a Master in Infection and Immunity at De Montfort University in Leicester (UK) in 1998. Then he joined the Department of Virology at Erasmus Medical Center in Rotterdam (NL), to obtain his PhD degree in 2003. After his PhD he joined the “Emerging Viruses” team of the same department where he worked on the pathogenesis of SARS-Coronavirus. Since 2008 he is team leader of the group “exotic viruses” of the Erasmus Medical Center Rotterdam. Since 2014 he is the Chief Scientific Officer of Artemis Bio-Support BV, where he focuses on the pathogenesis of emerging viral infections and develop intervention strategies against these diseases. Dr Martina has developed and implemented immunogenicity packages within Artemis Bio-Support to help map the correlates of protection and demonstrate the efficacy of vaccine or antivirals. He worked on development and evaluation of candidate vaccines against Dengue virus, West Nile virus, Japanese encephalitis virus, chikungunya virus, Rabies virus, Influenza virus and SARS coronavirus. He has ample experience with development and use of preclinical animal models and bio-analytical in vitro assays.
Zika virus (ZIKV), a previous mosquito-borne flavivirus, has attracted world-wide attention due to its close association with congenital Zika syndrome (i.e., microcephaly, fetal deaths, and other congenital malformations), and transmission through other routes, such as blood transfusion and sexual contact. Here, we have examined transfusion-transmitted ZIKV infection in ZIKV-susceptible pregnant mice and rationally designed effective ZIKV subunit vaccines with improved efficacy. Our data have shown that transfusion-transmitted ZIKV at the early infection stage caused significant viremia, broad tissue tropism, and severe placental and fetal infection, leading to fetal damage, fetal and pup death. In addition, a rationally designed subunit vaccine based on the ZIKV envelope protein domain III (EDIII) had improved efficacy in fully protecting mice, particularly pregnant mice and their fetuses, against high-dose lethal ZIKV challenge. Moreover, this EDIII protein vaccine formulated with a combination of aluminum and monophosphoryl lipid A adjuvants induced a more balanced immune response in mice and greater protection of mice against high-dose ZIKV infection, significantly reducing viral titers and viral RNA copy numbers in sera and tissues, including the male reproductive organs. Overall, our study has demonstrated the feasibility for further development of this protein into an effective subunit vaccine against ZIKV infection.
Dr. Lanying Du received her Ph.D. from the University of Hong Kong, and is currently an Associate Member and Head of Viral Immunology Laboratory at Lindsley F. Kimball Research Institute of New York Blood Center, USA. She has over 10 yearsï¿½ experience in designing and developing safe and effective vaccines against emerging infectious viruses with more than 100 published papers and several issued U.S. patents in the related research fields. The research focus of Dr. Du is to 1) develop novel, effective, and safe vaccines and therapeutic antibodies for the prevention and treatment of emerging and reemerging infectious diseases caused by coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and other coronaviruses with pandemic potential, influenza viruses, as well as transfusion-associated flaviviruses, including Zika virus (ZIKV); and 2) study pathogenic mechanisms of these viruses, based on which to design novel vaccines and therapeutic antibodies.
Immunity, in all its forms, has evolved to recognize and eliminate dangers from within, such as cancer, and the threat of pathogens from without. The enormous variety and lifestyles of infectious organisms has been the driving force for the development of an equally diverse immune system comprising intrinsic, innate and adaptive components, each capable of distinguishing self from non-self and selecting the most appropriate functional response from its wide range of effector mechanisms. Whatever strategy a pathogen employs for its propagation, all have evolved genes for the manipulation and subversion of the biology of the infected cell and the many defensive mechanisms of the host immune system. The study of these “evasion” genes may provide us with an exploitable source of new approaches for the control of both infectious and non-infectious diseases, for example, virus vaccines attenuated by deletion of gene(s) downregulating immune responses, and cancer therapy through the exploitation of virus strategies for manipulating the cell cycle and apoptosis. My presentation will review our work on (1) The application of African Swine Fever Virus genes inhibiting IFN response to vaccine development and (2) The development of a vaccine for cysticercosis based on an adhesion molecule essential for parasite invasion.
R Michael Parkhouse was first trained as a biochemist, and then an immunologist. His research has been in the area of infection and immunity. His postdoctoral experience at the Scripps and Salk Institutes in California, was followed by a permanent staff appointment at the National Institute of Medical Research, UK, a period of two years as a Director of the Centro Nacional de Biotecnologia, Spain, and then Head of Immunology at the Pirbright laboratory of the Institute for Animal Health, UK. Currently he is a group leader at the Gulbenkian Institute of Science, Portugal, where his research interests focus on host-pathogen interactions.
Two Kazakh regions (Almaty and Eastern Kazakhstan) are officially considered to be endemic for tick-borne encephalitis, but after analyzing the data of many years research in Kazakhstan, we concluded that 8 regions, i.e. most of the territory of Kazakhstan can be endemic for TBE. In this regard, there are questions about the prevalence of tick-borne encephalitis in Kazakhstan and its prevention in active foci. The events of the last years of 2017-2019 confirm our assumption, the cases of TBE were also registered in Akmola, North Kazakhstan, Kostanay, Zhambyl and even in two areas of which we did not consider endemic – Turkestan and Kyzylorda. We conducted a study of the effectiveness of vaccination against TBE with the vaccine "Encevir". Were examined it in 63 volunteers from among the military personnel of border troops, past two-time vaccination, with a difference of about 30 days. The ELISA study was conducted 8 months after vaccination. In 18 (28.6%) vaccinated no IgG antibodies were found at all, in 11 (17.5%) the optical density in the sera of the vaccinated was low - less than twice as much as compared with negative control. Only 12 (19%) vaccinated this the titer of IgG in serum exceeded the negative control in 5 and 8 (12.7%) – 10 or more times, which can be interpreted as sufficient for anti-infection protection level. Thus, more than a third of vaccinated people have no or insufficient immune response. Confirmation of this was the case of tick-borne encephalitis of one of the vaccinated – 5 months after vaccination, the diagnosis was confirmed in the ELISA by the detection of IgM (2,148/0,255) and IgG (2,891/0,130) already on the 5-6 day of the disease, which on the one hand indicates the secondary nature of this immune reaction, but also the lack of a protective effect from vaccination.
Andrey Dmitrovskiy is Professor of Infectious Diseases Department, Kazakh national medical University, where he worked from 2000, he is also head of laboratory in Kazakh National Center for Biotechnology Almaty branch, he was AECOM Sustainability Manager in KZ, 2011-2014, and he worked in CDC Almaty branch, 2006-2009. He received Ph. D. in infectious diseases at Central Institute of Epidemiology (Moscow, Russia) in 1984 and Doctor of Science in infectious diseases and epidemiology in the Kazakh scientific center for quarantine and zoonotic infections (Anti-Plague Institute) in 1999. In 1979 - 1999 he worked at this Institute as senior researcher and head of Department.
The world has made tremendous progress in immunization and vaccine delivery since the establishment of the expanded programme on immunization in May 1974. To realize the ambitions of the decade of vaccines, the Global Vaccine Action Plan (GVAP) was endorsed by the member states at the May 2012 World Health Assembly to prevent millions of deaths by 2020 through more equitable access to existing vaccines for people in all communities . By 2016, coverage has stagnated or barely improved . An estimated 19.5 million infants worldwide are still missing out on basic vaccines, with 60% of these children living in ten identified countries globally . Analysis across countries shows consistent patterns of deprivations in varying proportions. While there are hundreds of candidate vaccines under development, this paper seeks to examine whether or not the key bottlenecks to immunization services are being prioritized in vaccine research and development (R&D) tapping into the potential win-win for both supply and demand side. The immunizations supply chain barriers and Focus on addressing cold chain gaps. Cold chain equipment gaps, reducing wastage and delivery mechanisms will be detailed out using some field and published data. Resolving these challenges through vaccine R&D remains pivotal in advancing immunization coverage, with equity.
Ibrahim Dadari received his medical degree from College of Health Sciences, Ahmadu Bello University Zaria, Nigeria; and a Master in International Healthcare Management Economics and Policy (MIHMEP) from the SDA Bocconi School of Management in Milan Italy, specializing in Global Health and Development. He is an Immunization and Child Health Specialist with UNICEF. He has a number of publications in immunization and vaccinology, is a Reviewer Board Member for Vaccines and Immunology Open Access Journal. He has won a number of fellowships
Vaccine producers are facing the challenges of accelerating innovation, increasing capacity and reducing costs to make vaccines more available and more affordable. Legacy vaccines have been manufactured in stainless-steel based production plants that require considerable time and resources to operate and validate. The vaccines of the future will be produced in flexible ballroom facilities using closed single use systems, intensified production platforms, modern process analytical tools and predictive process controls. Next generation vaccine plants will be able to switch from mammalian, viral and bacterial systems to meet the key objectives of continuous quality improvement and capacity expansion at lower cost. This presentation first describes how using a fully automatic ambrï¿½ multi-parallel bioreactor testing tool and its associated DoE software can help optimize mammalian cells, insect cells, avian cells and bacteria expression systems. Upstream process intensification tools and real case data will be presented for both suspension and adherent cell culture in fed batch, concentrated fed batch or perfusion mode. Intensifying both the seed train and production bioreactor with perfusion can reduce half of the consumable costs and cell expansion time and provide 10 to 50 times higher cell density. Second, the first ambrï¿½ system applied to Downstream Processing, ambrï¿½ crossflow, capable of performing up to 16 trials in parallel, will be introduced to show how it can accelerate the optimization of the ultrafiltration and diafiltration steps. Case studies on adenovirus and influenza viruses purification will show how membrane chromatography that provides up to 10 times higher binding capacity than traditional resins and large-cut off cross-flow cassettes can further simplify and intensify the purification process of common vaccines. The author will finally show how the implementation of fully contained single use technologies, in line analyzers and SIMCAï¿½- on line multi variate monitoring tools can increase process flexibility and safety, provide predictive process control and lead to safer and cheaper vaccine manufacturing processes.
Piergiuseppe Nestola is a Global Vaccines Technology consultant at Sartorius Stedim Biotech where he is responsible for providing scientific leadership and identifying the best technologies and processes for the vaccine segment. Prior to joining Sartorius he worked for several years at Janssen Vaccines AG in Bern (CH) as a scientist and team leader in the process development group. In this role he was involved in the development and scaling up of both viral vectors and protein based vaccines. Since 2018 Piergiuseppe has also been acting as judge at the Mass challenge and Bioexpert network incubators supporting start-up life science companies. Piergiuseppe holds a PhD degree in Chemical and Biochemical engineering from Universidade Nova de Lisboa (PT) where he performed his research at iBET and developed virus purification processes for vaccines and gene therapies. Piergiuseppe has a Master Degree in Industrial Biotechnology from University of Turin (IT) and a certificate in disruptive innovation from IMD Business School, Lausanne (CH).
Vanessa is a Portuguese Biochemist that has been working in Vaccine development for nearly 10 years. She started by graduating from a Biochemistry degree at the University of the Algarve, from there she moved to the University of Leicester to work with Professor Peter Andrew and did her Doctoral thesis in the interactions of The Pneumococcus with mucin, particularly she studied 2 of the enzymes responsible for mucin de-glycosylation. In 2010, she became a member of Professor Brendan Wrenâ€™s Laboratory where she has been working in developing aspects of biological conjugation and applying it to vaccine development, mainly veterinary vaccines.
Sergey Suchkov graduated from Astrakhan State Medical University and awarded with MD, then in 1985 maintained his PhD at the I.M. Sechenov Moscow Medical Academy and in 2001, maintained his Doctorship Degree at the Nat Inst of Immunology, Russia. From 1987 through 1989, he was a senior Researcher, Kolt-zov Inst of Developmental Biology. From 1989 through 1995, he was a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, a Chair of the Dept for Clinical Immunology, Moscow Clinical Research Institute (MONIKI.DrSuchkov has been trained at: NIH; Wills Eye Hospital, PA, USA; Univ of Florida in Gainesville; UCSF, S-F, CA, USA; Johns Hopkins University, Baltimore, MD, USA. He was an Exe Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, Dr Sergey Suchkov is a Chair, Dept for Personalized and Translational Medicine, I.M.Sechenov First Moscow State Medical University. He is a member of the: New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Pre-dictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research); PMC (Personalized Medicine Coalition), Washington, USA.
The WHO malaria vaccine roadmap set two strategic goals to be met by 2030: i) the development of vaccines that are highly efficacious in preventing clinical malaria and ii) the development of vaccines that prevent transmission, to accelerate malaria parasite elimination. An efficacious vaccine must either be completely effective against a stage, by eliminating over time the parasite or dramatically reducing parasite numbers, or else target multiple stages of the parasite lifecycle. A recent study demonstrated that partially efficacious interventions separately targeting the pre-erythrocytic and sexual stages have a synergistic impact in eliminating malaria from a population over multiple generations. Very recently, our group generated a series of human adenovirus 5 (AdHu5) and adeno-associated virus serotype 1 (AAV1) expressing either P. falciparum pre-erythrocytic PfCSP or sexual stage Pfs25 antigen. Heterologous two-dose immunization with an AdHu5-prime and AAV1-boost elicited a high level of protection against sporozoite challenge and excellent transmission blocking (TB) activity with sustained high-titer antibody responses. Using the same platform, we have also developed AdHu5- and AAV1-vectored multi-stage vaccines harboring ‘the pfcsp-pfs25 fusion gene’. Transgenic P. berghei expressing either the pfcsp or pfs25 genes were used to evaluate the protective and TB efficacies of this candidate multi-stage vaccine in a murine model. Our results demonstrate that the multi-stage vaccine regimen has the potential to fulfill the landmark goals of the malaria vaccine technology roadmap by achieving sterile protection and long-term TB efficacy.
Shigeto Yoshida joined Kanazawa University School of Pharmacy as a professor in 2010. He received his two PhDs in Avian Virology and Immunology from Hokkaido University and in Malariology from Jichi Medical University, Japan. Bridging the fields of microbiology and immunology, he works to develop a new vaccine platform for infectious diseases. His research is now focused on malaria vaccine development. Recently, he has developed various viral‑vectored and recombinant protein‑based vaccine platforms capable of inducing long-lasting effective humoral and cellular ‘hybrid’ immune responses against malaria parasites in a murine model. He is also interested in parasite-mosquito interaction. His group has established both parasite- and mosquito-transgenesis systems to express foreign genes. He clearly aims to develop a new malaria vaccine for clinical setting. And his vaccine platform will be applicable not only for malaria but also other serious infectious diseases, such as Ebola, tuberculosis and HIV.
Porcine contagious pleuropneumonia, caused by Actinobacillus pleuropneumoniae (APP), is one of the most important pig infectious disease worldwide. To date bacterins and subunit vaccines are used in some countries/regions to prevent this disease. Although both forms of vaccines can provide a partial cross-protection for this multiple-serovar (â‰¥18) bacterium, most bacterins cause serious side effects (such as fever) due to containing high concentration of APP cultures of limited serovars, and subunit vaccines display limit of cross protection. Antimicrobial treatment therefore, remains the standard treatment for APP, and as such, is a leading driver of antimicrobial usage in pig farms. We have developed a composite vaccine namely â€œbacterin-subunit vaccineâ€ that consists of the inactivated bacterial whole cells of one strain (serovar 1) and three recombinant Apx toxins (ApxIA, ApxIIA, and ApxIIIA). The cross protection were evaluated in mouse infection model as well as in the natural host pigs by using virulent APP strains of serovars 1 and 5. Compared with the commercial tri-valent bacterin (serovars 1, 2 and 7) and subunit vaccine PorcilisÂ® APP, our bacterin-subunit vaccine showed a much higher cross protection, and lower side effects. The antibody titers of the three toxins were much higher and last longer in the immunised animals. Histopathological study revealed that the vaccinated pigs displayed much healthy lungs that have a significantly lower bacterial load. The preliminary data suggests that our composite bacterin-subunit vaccine is a promising vaccine for this death-causing economics-important disease. Its application in pig farms shall reduce the usage of antibiotics in food-producing animals, and be helpful for human and animal health.
The BCG vaccine against tuberculosis is the oldest vaccine currently in use. Its effectiveness is highly controversial with studies finding effectiveness between 0 – 80 % against pulmonary tuberculosis.. The aim of the present study was to estimate the effectiveness of BCG against latent tuberculosis in immigrant children coming to Sweden from high incidence countries, most of them being asylum seekers. As a substitute for BCG vaccination a typical BCG scar was used. 1091 patients were included in the study. In all of them the arms and legs were inspected for a BCG scar and Quantiferon was tested. 98 of 805 (12%) children with a BCG scar had latent tuberculosis while 63 of 288 (22 %) without a BCG scar had latent tuberculosis giving an estimated vaccine effectiveness of 44 %. In conclusion, latent TB is a problem among immigrant children and will spread in these population if all arrivals are not tested. Secondly the BCG vaccine has a low but statistically significant effect on latent tuberculosis.
This paper presents the work on Ebola virus (EBOV), including detection of serum anti-EboV and EboV RNA in humans, swines and chickens in East China. Background: Ebola virus was identified in 1976, and causes Ebola disease (EVD). The largest outbreak of EVD has been in West Africa, with more than 27,000 reported cases and more than 10,000 documented deaths. Etiology of Ebola virus : Long and thread-like, particle size 80x1000 nm, enveloped, and ether/ethanol sensitive, with linear and ssRNA genome (18.9kb). The possible receptors of EBOV are TIM-1, NPC-1, TPC, and natural host is fruit bats. Early detection and diagnosis are essential for treatment and control of EVD. Current detection methods being used: EBOV isolation (cell cultures), gene amplification (real-time qRT PCR), antigen detection (ELISA), and antibody detection (IFA, immunofluorescence assay). Objective- to investigate serum anti-EboV and EboV genes in humans and certain animals in East China. Samples- a) Healthy human sera (187 samples from the Blood Center in Shanghai). b) Healthy swine sera (139 samples from the Institute of Animal Husbandry & Veterinary Science, Shanghai Academy of Agricultural Sciences). c) Healthy chicken sera (118 samples from the IAHVS). Methods- Indirect immunofluorescence assay was used to detect serum antibody against Ebola virus GP-expressing cells (EboV GP antigen), and RT-PCR was used to examine EboV NP gene. H1N1 HA-expressing cells were used as control. Results: The positive rates of serum anti-H1N1 HA in healthy humans, swines, and chickens are 77.5% (145/187), 19.4 % (27/139), and 16.1% (19/118), respectively. But no serum anti-EboV GP and EboV NP gene were detectable in healthy humans (0/187), swines (0/139), and chickens (0/118). Conclusion: Unlike anti-H1N1 HA, serum anti-EboV and EboV RNA are not detectable in humans, swines and chickens in East China area. These findings suggest that humans in this area should be susceptible to future possible EboV infection, and that the preparedness would be crucial to potential EVD epidemic in East China area.
Worldwide vaccination introduction in the National Immunization Programs have contributed to control and prevent a considerable number of diseases. This is one of most relevant Public Health resources in the area of prevention and control of diseases and epidemics. The human-restricted bacterium Haemophilus influenzae is responsible for respiratory infections in both children and adults. While colonization begins in the upper airways, it can spread throughout the respiratory tract potentially leading to severe invasive infections. H. influenzae is divided into two major groups: non-encapsulated (NCHi) and encapsulated isolates, being the last group further characterized into six antigenically distinct serotypes (a through f), which differ in chemical and antigenic composition of the polysaccharide capsule, the major virulence factor. H. influenzae serotype b (Hib) has been a major cause of morbidity and mortality, being responsible for more than 95% of invasive disease. Prevention of Hib disease started in the early 1980s, with the license of the “first-generation Hib vaccine” that contained the pure polysaccharide of the Hib capsule. This vaccine was poorly immunogenic in children younger than 18 months. In the mid-1980s and in 1990s, Hib conjugate vaccines (PRP-OMP and PRP-CRM) were evaluated and considered immunogenic in children younger than 2 years of age. These vaccines were licensed and routinely used to prevent Hib disease that dropped dramatically soon after its introduction. In 2006, the World Health Organization (WHO) universally recommended the implementation of Hib vaccination in all infant immunization programs worldwide, which is currently in use in 192 countries, including all EU/EEA member states. Recently, other formulations of vaccines, including the aggregation of several antigens in the same injection, lead to an ultimate formula of a hexavalent vaccine (Hepatitis B, Hib, Diphtheria, Tetanus, Pertussis and Polio) that have showed good results in contributing to decrease Hib disease, with increase of coverage and maintaining effectiveness of previous vaccine combinations. With decline of Hib disease, the emergence of infections by other serotypes as well as by NCHi have been observed, highlighting the need for the development of new vaccines such as a vaccine against NCHi disease. Several studies have been conducted, but the development of an effective vaccine against NCHi is still an ongoing subject of research.
Brucellosis is a significant problem for public health and veterinary service for Kazakhstan. So in recent decades there has been a significant increase in the incidence of brucellosis in people - the average annual absolute increase in the incidence of primary diagnosed brucellosis was 1,28, the total increase – 89,37%. More than 3.5 thousand cases of new brucellosis are detected annually. Naturally, the main source of infection with brucellosis are farm animals, primarily small cattle. In this regard, there are several problems associated with brucellosis in Kazakhstan. The problem of laboratory diagnosis is that traditionally bacteriological method is used for the laboratory diagnosis of brucellosis in humans. The percentage of bacteriological confirmation cases is about 10%, almost all the isolated strains are Brucella melitensis. The remaining cases are confirmed by agglutination serological methods that do not allow to differentiate the Brucella species, as well as in animals. The problem of specific prevention – vaccination against brucellosis. Until 2000, Kazakhstan used human vaccination against brucellosis with a live Brucella abortus vaccine strain 19. This vaccination did not protect people from infection with brucellosis, how much was caused by a specific sensitization that could lead to the emergence of the clinic of chronic brucellosis without the presence of infection. The animals used the same vaccine, then moved to the vaccine strain Brucella abortus strain 82, and then caused by Brucella melitensis strain Rev 1. Unfortunately, in the veterinary field in Kazakhstan has not developed an effective program not only vaccination against brucellosis, but generally struggle with this infection. Currently, routine vaccination of farm animals is not carried out at all, every farmer can buy any vaccine available on the market and apply it haphazardly. As a result of this, brucellosis of animals is increasing in Kazakhstan and the incidence of people is growing.
The herpesviral vaccines inactivated with formaldehyde or β-propiolactone are manufactured from the viruses grown in the cell cultures, Vero B (herpes simplex virus types 1 and 2), and diploid human fibroblasts (cytomegalovirus (CMV), herpes zoster virus). The vaccines are planned to be manufactured in two pharmaceutic forms, for parenteral (intracutaneous) injection, and for suppositories. These inoculation routes allow to avoid allergic reactions given that anti-herpetic vaccines take multiple inoculations during infection. The immunogenicity of the developed vaccines is examined in lab animals. The herpesviral vaccines suggested for manufacture meet the criteria of the Global Vaccine Quality Programme and are free from the drawbacks typical for live herpesviral vaccines, and also they are safe to apply in persons with compromised immunity.
Background: Effective vaccines against yellow fever virus have been in use since 1937. The World Health Organization (WHO) currently recommends the use of a single dose of yellow fever vaccine for life and fractional doses in outbreak situations where vaccine doses are limited. Measles vaccines have also been in use for decades, yet sporadic epidemics are on the increase. In endemic regions, yellow fever and measles vaccines are given as part of the routine infant immunization programmes. There is a need to better understand factors that may affect the immune response when infant vaccine doses are used particularly when used concomitantly with other vaccines. Methods: Data from 393 infants (for yellow fever response) and 1,105 (for measles response) in Mali and Ghana who received MenAfriVac, measles and yellow fever vaccines concomitantly at 9 to 11 months of age was analysed. Neutralizing IgG antibody (Ab) titres/concentrations induced by yellow fever and measles vaccines were assessed with respect to nutritional status, sex, age, pre-existing antibody and season of vaccination. We also examined the seroconversion rates. Results: Seroconversion rates for yellow fever were significantly different between the 2 countries. Responses were largely unaffected by the covariates studied. Only 0.4% of infants had protective anti-measles Ab concentrations pre vaccination. Conclusion: Several factors may play a role in varying vaccine responses including vaccine formulations and genetics. Virtually all children were vulnerable to measles infection by 9 months of age which may suggest a need for earlier vaccination. Systematic studies are needed to optimize the use of yellow fever and measles vaccine in endemic settings.
Notoriously, that multiple myeloma (MM)-B-lymphoproliferative disease, occurs at the level of the germinal center of the lymph nodes, the main morphological substrate of which is plasma cells. Today, the early diagnosis, detection complications, target treatment of multiple myeloma and their consequences worry us all. Multiple myeloma (MM)diagnosed on the basis of classical, standard criteria: plasma cells in a bone marrow puncture more than 10%, the presence of monoclonal protein and osteodestructive lesions, as well as are used the proposed characteristics classifications [1; 2; 3] and is evaluated damage target- organ by dint of diagnostic CRAB -criteria, according to the schemes proposed by studying myeloma International Myeloma Working Group[4,5]. Is considered MM, as an elderly disease, but in recent years it has a tendency to the rejuvenate the disease, found at a younger age. At the early diagnosis of multiple myeloma without signs of complications and timely standard targeted therapy (immunomodulatory drugs (UTIs) and proteasome inhibitors) give fairly long-term remissions, if necessary with spend by indication autotransplantation bone marrow. In the elderly age and in a young age, after achieving the remission of targeted therapy, with rare forms of immunoglobulin’s, recurrent or refractory multiple myeloma, if necessary, according to indications, if there is a compatible HLA-donor, spend allogenic transplantation (AlloT) hematopoietic stem cells transplantation. However, in multiple myeloma, cell therapy with closely related haploidentical transplantation (parent, brother, sister, child or placental blood) has a high percentage of compatibility and immunotherapy (on the basis vaccines dendritic cells) will give the best results and will find its use in the future. At the multiple myeloma refractory or recurring, or with rare forms of immunoglobulin’s and with early visits by patients to doctors, where the current of the disease to flow and in young and old, more malignant and aggressively. As authors [6,] describes, that the disease MM is often detected in the later stages, there are no criteria in changes the blood, which are markers of malignancy, especially in the early stages of its development, in this connection, it is necessary to study immunoglobulin’s for potential bone marrow donors for the content of free light chains with prophylactic purposes. The selection of a donor is necessary with a thorough collecting anamnesis and attentively examination. It is necessary to start donor from simple studies such as in the virus Epstein-Barr, cytomegalovirus, antibodies IgG to H. pylori infection to complex expensive HLA-genes. On the principle, do not harm neither the donor, neither the patient. [7,8]. As the authors note, during selection of an unrelated donor, it must be taken into account that the patient and the donor cannot match the alleles of the HLA-C gene. And recommends expanding the cohorts of HLA-A *, B *, C *, DRB1 *, DQB1 * of typed donors in bone marrow registers.. The aim of our study is on the based on comprehensive clinical-hematological, immunogenetic studies of patients multiple myeloma and donors hematopoietic stem cells, timely detection at the early stage of the disease and determine the medical-social, economic-legal status of donors hematopoietic stem cells.
Endotoxin is heat-stable lipopolysaccharide (LPS) present in outer membrane of cell wall of Gram negative bacteria. All parenteral preparations as well as tissue implants must be with no pyrogenic level of endotoxin or other related materials because of their associated health hazard and serious clinical effects. Accordingly, detection and limiting endotoxin in various pharmaceutical and biological products represent crucial issue. Rabbit pyrogen test (RPT) and Limulus Amebocyte Lysate (LAL) test are two methods used for endotoxin detection and quantification. Endotoxin detection is one of the most critical quality control tests required by Food and Drug Administration (FDA) for all parenteral drugs in their final stage. Both in vitro LAL test and in vivo RPT can complement and reinforce each other but in certain cases they are not interchangeable and they together provide a comprehensive picture of any potential contamination whether by endotoxin or any other pyrogenic matters.
In 2016/17 Nigeria conducted combined multi-indicator and national immunization cluster surveys with support of WHO and UNICEF considering the demographic characteristics which significantly affect vaccination coverage. Data expressed a gross decline in vaccination coverage comparative to 2006 and 2010 surveys which is an alarming sign for the whole immunization program in Nigeria. Measuring vaccination dropout rate, the principle indicator to assess the quality of the Immunization program for its access and utilization. Dropout rates greater than 10 percent indicate serious service quality problems which was more than 31% for most of antigens for Nigeria at national levels. Vaccine quality indicators were only computed as valid for children whose home-based records were available while the card retention was only 29 percent nationally. Crude national coverage was 53% while valid coverage only 26% depicted sensitivity levels of parents for card retention. Main reasons for non-vaccination were lack of knowledge and awareness as well as service access & delivery issues. In states where good vaccination coverage was noted , maternal and child health status was also better comparative to those states where immunization services were poor and vice versa. More epi centers in proportion to population size & geographical access with more human resources , timely logistic supplies, more effective monitoring and supervision, improved budgets, effective and sufficient social mobilization campaigns, education and economic well being are directly linked with vaccination coverage so political , economical and educational stability is the key to success among other factors and this is well proved from the survey data.
Interactive experiments to reach the best programs of vaccination and getting of the highest immune response. In first study two vaccines were prepared, Romanian sheep pox (RSP) and Ismailia lumpy skin disease (LSD) vaccines, they were evaluated and proved sterile and potent, and were used for vaccination of susceptible calves against lumpy skin disease for selection of the most appropriate one , depending on their protectively effect. The acquired humoral and cellular immunity were evaluated by neutralization test and lymphocyte blastogenesis assay, measured by XTT assay. The results proved that the second vaccinated group (with LSD vaccine) acquired a slight prominent immunity more than (RSP vaccine) .generally both of Romanian SP and Ismailia LS vaccines can protect the cattle from infection with lumpy skin disease. In addition the experiment was applied on groups of calves, each group were vaccinated with one of the following attenuated vaccines: Lumpy skin disease vaccine (LSD), Romanian sheep pox (RSP) vaccine, Held goat pox (HGP) vaccine and dual (bivalent) vaccine, of Romanian SP and Held GP experimental vaccine (as mixed with each others at the ratio of 1:1 (v: v) of equal titers (104.5 of SPV and GPV). Also vaccines were evaluated by estimating the cellular immunity using lymphocyte blastogenesis and humeral immunity using NI and ELISA tests of vaccinated calves. The NI coincided with the ELISA antibody results and corroborated the results of cell mediated immunity which demonstrated the capacity of LSD and dual vaccines to induce immune response higher than RSP vaccine and HGP vaccines. In conclusion, the study proved that the LSD and dual vaccines were highly immunogenic than the RSP and HGP vaccines, and dual vaccine could be safely used for vaccination of cattle against lumpy skin disease. Also the presence of various live attenuated vaccines have existed from time to time for capripox with varying degrees of protective efficacy in different countries and sometimes within the same country. An experiment applied on groups of susceptible calves, were individually inoculated intradermally (I/D) or subcutaneously (S/C); in the tail fold. In order to pinpoint the optimum program of vaccination against lumpy skin disease one of the alternative vaccination programs by using attenuated Lumpy skin disease (LSD) vaccine, attenuated Romanian sheep pox (RSP) vaccine and inactivated LSD vaccine (separate; simultaneous or successive); beside control isolated non vaccinated animals . Sera samples were collected before and weekly after vaccination from all animals. The humoral immunity was checked out by serum neutralization test (SNT) and enzyme linked immunosorbent assay (ELISA) for 6 months post inoculation, while the cell mediated immune response was performed by the hypersensitivity reaction at the inoculation site after I/D inoculation with 0.5 ml of attenuated LSD vaccine and its results corroborate the humoral results. The results of humoral and cellular immunity proved that successive vaccination of cattle with live attenuated RSP vaccine prior to the inactivated LSD vaccine create relative acquired immunity subsequent to the homologous live attenuated LSD vaccine and overcome the immunological effect of the other used vaccines. Our results nominate the homologous attenuated LSD vaccine and successive vaccination with attenuated RSP vaccine before inactivated LSD vaccine for absolute protection of cattle from LSD. It was concluded that the successive vaccination (with attenuated RSP vaccine before inactivated LSD vaccine) is considered safer and avoid viral reversion and transmission of the virus by the blood feeding arthropods. Keywords: LSD, SP, successive vaccination, capripox, inactivated, cattle.
There is an emerging interest in understanding how the cystic fibrosis (CF) bacterial pathogens interact and how they influence CF pathogenicity. This interest is influenced by the appreciation that, from a microbial ecological standpoint, microbes do not exist as individuals but function as a structured community. The microbe-host interactions, of the co-existing pathogens, appear to play an important role in the pathogenesis of polymicrobial infectious diseases like CF. It is therefore believed that a key to the discovery of a vaccine, for these infectious diseases, lies within these bacterial-host interactions. In this study, the differentially expressed proteomic profiles of mixed cultures of the three bacterial pathogens of interest, that is Burkholderia cepacia (B. cepacia), Pseudomonas aeruginosa (P. aeruginosa) and Staphyloloccus aureus (S. aureus), were determined and assessed. The aim was to identify the immunoresponsive antigens among those that are differentially expressed in mixed culture when compared to individual cultures. The study employed the use of TCA/Acetone for protein extraction. The extracted proteins in lysis buffer were resolved in triplicate on two dimensional SDS-PAGE using 7 cm, pH 3-10, immobilized pH gradient (IPG) strips. The immunoresponsive antigens were visualized on Western blots following treatment with CF positive sera. The differentially expressed vaccine antigenic candidates, detected in the secretome, that are immunoresponsive to CF patient sera, were identified and explored for use as vaccine candidates, in silico.