Biological challenges to effective vaccines: learning from variation in vaccine immunogenicity and efficacy

Professor Mulholland is an Australian paediatrician with extensive experience in research leading to or evaluating the introduction of new vaccines in the developing world. Between 1989 and 1995 he lead the Hib vaccine research program in the Gambia, which involved three Phase 2 trials of Hib vaccine, a maternal immunisation study and a large Phase 3 trial. The latter study formed the prototype for future pneumococcal vaccine trials. Between 1995 and 2000 he worked at WHO Geneva, where his work included assistance with the design and oversight of the Gambian and South African pneumococcal trials. He also established the pneumonia trialists group that established standardised methods and definitions for pneumococcal carriage and radiological pneumonia in vaccine trials. Since 2000 he has worked in academic institutions in the UK (London School of Hygiene and tropical Medicine) and Australia (Menzies School of Health Research, Darwin and Murdoch Childrens Research Institute, Melbourne). During that time he has established pneumococcal research programs in Fiji and Vietnam. He currently leads the Gates funded PneuCarriage Research Project, based at MCRI, as well as field studies in Fiji (PCV10 impact study), Mongolia (PCV13 impact/effectiveness study), Laos (PCV13 impact study), Indonesia (PATH funded pneumococcal Whole Cell Vaccine evaluation) and Vietnam (PCV10/PCV13 schedules study). In addition he remains involved in Hib and PCV impact studies in the Gambia.

Paul Fine trained in veterinary medicine in the US, and in epidemiology in the UK, worked in the smallpox eradication program in India and spent a year at University of California, Berkeley working on arboviruses, before joining the staff of the London School of Hygiene and Tropical Medicine in 1976. His major research interests have been in infection dynamics, family studies, genetics, and in the evaluation of vaccine efficacy, effectiveness, adverse reactions and impact, applied to a variety of infections. He directed a large epidemiological research programme (the "Karonga Prevention Study") in Malawi from 1978-2006, which included a trial of vaccines against leprosy and tuberculosis. Recent interests in vaccines have included the implications of the transmissibility of oral polio vaccine virus for the global polio eradication programme, the assessment and implications of “non-specific effects” of vaccines, evaluation of veterinary vaccines, and procedures for the optimization of vaccination schedules in developing countries.

Dr Parashar is the Lead of the Enteric Viruses Epidemiology Team in the Division of Viral Diseases at the US Centers for Disease Control and Prevention (CDC).  Dr Parashar completed medical school in India and then completed postgraduate training in Public Health and Preventive Medicine in the United States. He joined the CDC as an Epidemic Intelligence Service Officer in 1996 and has spent more than 17 years at CDC researching the epidemiology of viral gastroenteritis and methods for its prevention and control, including vaccination strategies against rotavirus gastroenteritis. He was the CDC co-lead of the working group that developed the recommendations for use of the new rotavirus vaccines in the United States. The CDC Enteric Viruses Team also leads the Disease Burden and Surveillance Activities of the Rotavirus Vaccine Program (RVP), a partnership between the CDC, World Health Organization, and Program for Applied Technology in Health that is supported by the Global Alliance for Vaccines for Immunization. The RVP conducted activities to accelerate introduction of rotavirus vaccines in developing countries with the greatest burden of rotavirus disease. Dr Parashar has published more than 250 scientific papers and book chapters and has given numerous peer-reviewed and invited presentations and scientific conferences. He has also served as guest editor on 4 supplements for leading scientific journals and on advisory committees to the World Health Organization. He has received several awards, including the Oswald Avery Award for Early Achievement from the Infectious Disease Society of America, the Shepard Award for Best Scientific Paper in the Prevention and Control Category from the CDC in 2009, and six awards for Distinguished Service from the Secretary of the US Department of Health and Human Services.

Adrian Hill trained at Trinity College Dublin and Oxford is now Professor of Human Genetics and Director of the Jenner Institute at Oxford University. He leads research programmes in genetic susceptibility to tropical infectious diseases and in vaccine design and development.

As a founder member of the Wellcome Trust Centre for Human Genetics since 1994 his research group has studied multiple genetic factors associated with or genetically linked to resistance to malaria, tuberculosis, bacterial pneumonia, and viral infections such as hepatitis B and C and HIV. His group has pioneered genome-wide linkage and association analyses of genetic susceptibility to common human infectious diseases, particularly tuberculosis, more recently as part of the Wellcome Trust case control consortium. Data on immunogenetic susceptibility factors have provided new insights into the impact of infections on human genomic diversity. 

He has published over 350 research papers, is a Fellow of the UK Academy of Medical Sciences and the Royal College of Physicians, and a NIHR Senior Investigator.

Andrew J Pollard, FRCPCH PhD, is Professor of Paediatric Infection and Immunity at the University of Oxford, Director of the Oxford Vaccine Group, James Martin Senior Fellow, Jenner Institute Investigator, Fellow of the Infectious Disease Society of America, Fellow of St Cross College and Honorary Consultant Paediatrician at the Children’s Hospital, Oxford, UK. He obtained his medical degree at St Bartholomew’s Hospital Medical School, University of London in 1989 and trained in Paediatrics at Birmingham Children’s Hospital, UK, specialising in Paediatric Infectious Diseases at St Mary’s Hospital, London, UK and at British Columbia Children’s Hospital, Vancouver, Canada. He obtained his PhD at St Mary’s Hospital, London, UK in 1999 studying immunity to Neisseria meningitidis in children and proceeded to work on anti-bacterial innate immune responses in children in Canada before returning to his current position at the University of Oxford, UK in 2001. He chaired the UK’s NICE meningitis guidelines development group, the NICE topic expert group developing quality standards for management of meningitis and meningococcal septicaemia. He received the 2013 Bill Marshall Award of the European Society for Paediatric Infectious Disease. He chairs the Department of Health’s Joint Committee on Vaccination and Immunisation and the European Medicines Agency scientific advisory group on vaccines. He runs one of the largest research groups in the UK that undertakes clinical trials in children and adults with 70 staff. Current research activities include clinical trials of new and improved vaccines for children and adults, surveillance of invasive bacterial diseases and impact of pneumococcal vaccines in children in Nepal, studies of cellular and humoral immune responses to glycoconjugate, RSV and typhoid vaccines, development of serogroup B meningococcal vaccines and research on a human challenge model of typhoid and paratyphoid. His publications include over 200 manuscripts and books on various topics in paediatrics, infectious diseases, and high altitude medicine.

Dr Chrissie Jones is an Associate Professor in Paediatric Infectious Diseases at the University of Southampton. Her research interests include interventions in pregnancy to prevent infection in early life. She has particular expertise in the field of maternal vaccination and leads pertussis and RSV clinical trials in pregnancy. She serves on the executive committee of GAIA (http://gaia-consortium.net), a large international consortium. As part of this initiative, Dr Jones has authored international guidelines to provide a standard for data collection in clinical trials of vaccines in pregnancy, which are recommended by the WHO. 

Dr Jones is the chief investigator of RACE-FIT, a NIHR-funded feasibility study to assess an educational intervention to reduce the risk of CMV acquisition in pregnancy. 

With postgraduate training in medical education, Dr Jones is involved with multiple initiatives to train and equip others in paediatric infectious diseases.

Mihai Netea was born and studied medicine in Cluj-Napoca, Romania. He completed his PhD at the Radboud University Nijmegen, The Netherlands, on studies investigating the cytokine network in sepsis. After working as a post-doc at the University of Colorado, he returned to Nijmegen where he finished his clinical training as an infectious diseases specialist, and where he currently heads the division of Experimental Medicine, Department of Internal Medicine, Nijmegen University Nijmegen Medical Center. His main research interests are pattern recognition of fungal pathogens and the induction of antifungal immunity, primary immunodeficiencies in innate immune system, and the study of the memory traits of innate immunity.

Professor Nicholas Grassly is an infectious disease epidemiologist with a background in biology and mathematics. Grassly heads the Vaccine Epidemiology Research Group in the Department of Infectious Disease Epidemiology, which focuses on characterizing the immunogenicity and effectiveness of vaccines at the individual and population level, with a particular interest in poliovirus. In collaboration with researchers in Asia and Africa, Grassly is carrying out epidemiological studies and clinical trials to characterize the immune response to oral vaccines. A major current interest is the interaction between the intestinal microbiota and the immune response to vaccines against poliovirus and rotavirus. Grassly's group also works closely with the Global Polio Eradication Initiative to ensure eradication activities are aligned with the best possible epidemiological evidence. This work was recognized in 2013 by designation as the WHO collaborating institute for polio data analysis and modelling.

Dr Shamez Ladhani completed his medical training at the United Medical and Dental Schools of Guy’s and St. Thomas’s Hospitals, London, and subsequently specialised in paediatrics. In 2000, he worked in Kenya as a paediatric registrar in a district hospital and then went on to complete a PhD in genetic epidemiology of vaccine preventable infections. During 2007-09, he completed the two-year national grid training programme in paediatric infectious diseases at St. George’s Hospital in South London. Currently, he works as a paediatric infectious disease consultant at St. George’s Hospital, clinical lecturer at St. George’s University of London and clinical epidemiologist at Public Health England. He is the clinical lead for enhanced national surveillance of a number of vaccine-preventable infections, including Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis and Rotavirus. He is also involved with conducting clinical trials on behalf of the Department of Health to inform national immunisation policy.

Dr Maldonado is Professor, Departments of Pediatrics and of Health Research and Policy; Chief, Division of Infectious Diseases; and Senior Associate Dean of Faculty Development and Diversity at Stanford University School of Medicine, USA.  Dr Maldonado’s research interests are the epidemiology and prevention of viral vaccine preventable infections, such as measles, polio, rotavirus, conducted internationally in Zimbabwe, Mexico, as well as in the US. She is a Fellow of the American Academy of Pediatrics and the Infectious Disease Society of America, a member of the Society for Pediatric Research, the Pediatric Infectious Disease Society and the American Public Health Association.

Dr Thomas Scriba is Associate Professor at the University of Cape Town and Deputy Director, Immunology, at the South African TB Vaccine Initiative (SATVI), a large research group focusing on development of new tuberculosis vaccines. He leads a clinical immunopathogenesis of TB laboratory and has led the immunology analysis for more than 10 clinical trials of novel TB vaccines, conducted in a setting highly endemic for TB.

Scriba is member of several international working groups on biomarkers and vaccine immunology and is actively involved in postgraduate training. He received bachelors and masters degrees from the University of Stellenbosch and a DPhil from Oxford University, and trained in pediatric and clinical immunology in tuberculosis and vaccinology at SATVI in Cape Town as a postdoctoral fellow.

Dr Kollmann completed his MD and PhD at the Albert of Einstein College of Medicine, Bronx NY, followed by a residency in paediatrics and fellowship in infectious diseases at the University of Washington, Seattle, WA. He now is consulting physician in paediatric infectious disease at BC Children’s Hospital, where he directs the training programme in Global Pediatric Infectious Diseases (GpID) and the Vancouver Immune and Vaccine Analysis Research Center (VIVArc). Dr Kollmann focuses on the development of the immune system, with a special focus on infections and vaccines for early life.

Allan Saul has been the Director of the Novartis Vaccines Institute for Global Health since its creation in 2007. This Institute, located in Siena Italy, has a mission to develop effective and affordable vaccines for neglected diseases of impoverished countries and its role is the translational research required to take vaccines specifically designed for the third world from laboratory concept though pilot scale production to proof of concept in humans.

He held previous appointments at the National Institutes of Health, USA where he was the co-branch chief of the Malaria Vaccine Development Branch and at the Queensland Institute of Medical Research, Brisbane, Australia.

NVGH currently has vaccines in pre-clinical or clinical development for Typhoid and Paratyphoid Fever, Shigellosis, invasive Nontyphoidal Salmonellosis in Africa and a vaccine for meningococcal meningitis also for Africa. NVGH has other vaccines at an earlier stage of development.

Gagandeep Kang received her training in medicine and microbiology at the Christian Medical College, Vellore in southern India and is currently a Professor in the Division of Gastrointestinal Sciences. She works on enteric infections in children, particularly on transmission and immune responses, in order to design effective interventions. Current studies include active hospital and community based surveillance and clinical trials of new and existing vaccines, with the use of molecular based assays to study the diversity of pathogens and the immune response of children with viral and parasitic enteric infections.

Professor Beate Kampmann holds a Chair in Paediatric Infection & Immunity at Imperial College, London and was appointed as the Scientific Director (Theme Leader) for Vaccinology research at the MRC Unit-The Gambia in July 2010. She leads a comprehensive childhood infection research program both in the UK and sub-saharan Africa, where she spends a third of her time. She has extensive practical and research experience in childhood infection for over 15 years and brings an established funding track record as PI and co-applicant from major international funders for the conduct of laboratory-based and programmatic research in TB and Vaccinology in both resource-poor and resource rich settings. At the MRC Unit in The Gambia, she directs all research activity in infant immunology, ranging from basic research of innate and acquired immune responses to infection and vaccination to clinical trials of novel vaccines and their adjuvants.

Professor Nicholas Grassly is an infectious disease epidemiologist with a background in biology and mathematics. Grassly heads the Vaccine Epidemiology Research Group in the Department of Infectious Disease Epidemiology, which focuses on characterizing the immunogenicity and effectiveness of vaccines at the individual and population level, with a particular interest in poliovirus. In collaboration with researchers in Asia and Africa, Grassly is carrying out epidemiological studies and clinical trials to characterize the immune response to oral vaccines. A major current interest is the interaction between the intestinal microbiota and the immune response to vaccines against poliovirus and rotavirus. Grassly's group also works closely with the Global Polio Eradication Initiative to ensure eradication activities are aligned with the best possible epidemiological evidence. This work was recognized in 2013 by designation as the WHO collaborating institute for polio data analysis and modelling.

Andrew J Pollard, FRCPCH PhD, is Professor of Paediatric Infection and Immunity at the University of Oxford, Director of the Oxford Vaccine Group, James Martin Senior Fellow, Jenner Institute Investigator, Fellow of the Infectious Disease Society of America, Fellow of St Cross College and Honorary Consultant Paediatrician at the Children’s Hospital, Oxford, UK. He obtained his medical degree at St Bartholomew’s Hospital Medical School, University of London in 1989 and trained in Paediatrics at Birmingham Children’s Hospital, UK, specialising in Paediatric Infectious Diseases at St Mary’s Hospital, London, UK and at British Columbia Children’s Hospital, Vancouver, Canada. He obtained his PhD at St Mary’s Hospital, London, UK in 1999 studying immunity to Neisseria meningitidis in children and proceeded to work on anti-bacterial innate immune responses in children in Canada before returning to his current position at the University of Oxford, UK in 2001. He chaired the UK’s NICE meningitis guidelines development group, the NICE topic expert group developing quality standards for management of meningitis and meningococcal septicaemia. He received the 2013 Bill Marshall Award of the European Society for Paediatric Infectious Disease. He chairs the Department of Health’s Joint Committee on Vaccination and Immunisation and the European Medicines Agency scientific advisory group on vaccines. He runs one of the largest research groups in the UK that undertakes clinical trials in children and adults with 70 staff. Current research activities include clinical trials of new and improved vaccines for children and adults, surveillance of invasive bacterial diseases and impact of pneumococcal vaccines in children in Nepal, studies of cellular and humoral immune responses to glycoconjugate, RSV and typhoid vaccines, development of serogroup B meningococcal vaccines and research on a human challenge model of typhoid and paratyphoid. His publications include over 200 manuscripts and books on various topics in paediatrics, infectious diseases, and high altitude medicine.

Adrian Hill trained at Trinity College Dublin and Oxford is now Professor of Human Genetics and Director of the Jenner Institute at Oxford University. He leads research programmes in genetic susceptibility to tropical infectious diseases and in vaccine design and development.

As a founder member of the Wellcome Trust Centre for Human Genetics since 1994 his research group has studied multiple genetic factors associated with or genetically linked to resistance to malaria, tuberculosis, bacterial pneumonia, and viral infections such as hepatitis B and C and HIV. His group has pioneered genome-wide linkage and association analyses of genetic susceptibility to common human infectious diseases, particularly tuberculosis, more recently as part of the Wellcome Trust case control consortium. Data on immunogenetic susceptibility factors have provided new insights into the impact of infections on human genomic diversity. 

He has published over 350 research papers, is a Fellow of the UK Academy of Medical Sciences and the Royal College of Physicians, and a NIHR Senior Investigator.