Despite the overwhelming global response to the crisis and the rapid mobilisation of candidate vaccines through trials, little could be done to control the spread of disease at the time. The Coalition for Epidemic Preparedness Innovations CEPI was established in the wake of this epidemic to fund the research and development of diagnostics, therapies and vaccines for epidemic infectious diseases EIDs to prevent a repeat of such a catastrophe Its priorities include pathogens associated with recent outbreaks such as severe acute respiratory syndrome SARS coronavirus, Ebola and Zika virus, and several other emerging pathogens and neglected tropical diseases NTDs.
The UK Vaccine Network focuses on the development of vaccines against prioritised diseases through the cooperation of academic institutions, the National Health Service NHS and pharmaceutical companies Collaborative efforts between scientists and between academia and industry will be vital for tackling future epidemics.
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There is much research to be done on known pathogens which represent possible threats and have not been as extensively characterised as those which have attracted the most funding in the past. This disparity can only be resolved by incentivising investment in research and development.
On the other hand, the next threats to global health may be totally unknown. Recent outbreaks have increased awareness of the importance of scientific surveillance and potential pandemic control measures. Improving preparedness for the emergence of novel pathogens will rely more heavily on the mandatory reporting of surveillance data, the international flow of information to provide rapid and effective control, and the development of platform technologies into which components of new pathogens can be inserted in the rapid development of new vaccines.
There are several diseases of varying prevalence and severity which represent a significant burden to health care systems in many countries and for which no licensed vaccine currently exists. As the leading cause of infant hospitalisation worldwide, respiratory syncytial virus RSV warrants particular attention.
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RSV is a significant cause of morbidity and mortality in infants worldwide and, considering its burden, is the most important infant disease which can be prevented by a vaccine for which no licensed vaccine exists The virus causes respiratory tract infections RTIs which range from mild upper RTIs to severe lower RTIs, with up to half of children suffering from the latter developing recurrent wheezing or asthma After malaria, RSV is the leading cause of infectious death in infants worldwide and is responsible for approximately 6.
At the time of writing June there were 59 vaccine candidates in various stages of development, 16 of which were undergoing clinical evaluation Maternal immunisation is being considered as a possible strategy for the prevention of RSV infection in early infancy, a time at which direct vaccination may be poorly effective Indeed, one candidate has been demonstrated safe and immunogenic in pregnant women and a Phase III clinical trial has been initiated to determine its efficacy Maternal immunisation has become an important approach to providing early protection in neonates and simultaneously offering a level of protection to pregnant women.
During the natural course of a pregnancy, IgG antibodies are transferred from the mother to the developing foetus across the placental barrier via the neonatal Fc receptor FcRn present on syncytiotrophoblast cells, conferring passive immunity For diseases such as pertussis which have peak incidence in the first months of life, maternal immunisation could provide protection for babies prior to receiving active routine immunisation in early infancy. A GBS candidate vaccine has also recently been shown to be safe and immunogenic in pregnant women The global availability of an effective vaccine against GBS would relieve the burden of perinatal disease associated with this pathogen.
Congenital CMV infection affects 0. The challenge to create a vaccine which could provide protection in utero is ongoing and deployment of such a vaccine prior to conception will likely require programmes aimed at childhood, and possibly prior to primary infection, i. Group A streptococcus is another very common pathogen which has a diverse range of clinical manifestations, is associated with a significant global burden and disproportionately affects children of indigenous communities such as in Australia and New Zealand Several vaccines are under development and data on efficacy are eagerly awaited Another challenge is the growing problem of infection acquired in the hospital setting.
HCAIs are responsible for extended hospitalisation at a significant cost to both patient and health systems. A comprehensive report published by the WHO in outlines in detail the global health burden caused by endemic HCAIs and makes a strong case for vaccine interventions The WHO recently published a list of a dozen families of bacteria which represent a serious threat to public health as a result of their acquisition of resistance genes Among these pathogens, Acinetobacter baumannii , Pseudomonas aeruginosa and Enterobacteriaceae were cited as being of highest priority.
Research into developing vaccines against several of these bacteria is ongoing but is hindered by the lack of known correlates of protection and animal challenge models in which these can be demonstrated.
There are a number of challenges in vaccine development that have hampered development of vaccines against important pathogens such as HIV, malaria and tuberculosis TB. These challenges arise largely because of the ability of these difficult pathogens to evade and manipulate the host immune response. In the case of HIV and HCV it is the considerable variability of protein sequence which develops during infection, which makes development of an inactivated vaccine based on a single sequence ineffective.
Further understanding of the immune response to HIV may eventually provide the solution. For these reasons, a preventive vaccine would be the most effective means of reducing the global burden of chronic liver disease associated with the virus. In addition to the antigenic variation of Plasmodium falciparum, the complexity of the parasite's life cycle presents a unique challenge to the identification of what constitutes a protective immune responses against the pathogen.
To this end, challenge studies have been particularly informative for malaria vaccine development and had an important role to play in the optimisation of the malaria RTS,S vaccine The establishment of phase I trials and human challenge studies in endemic regions is enhancing optimisation of malaria vaccines for target populations.
TB vaccine development would benefit greatly from the identification of new correlates of protection and animal models which more accurately reflect the progression of human TB.
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The importance of basic immunology research in vaccine development is highlighted when prevailing hypotheses are rejected following failure in vaccine efficacy studies. This type of research is essential for addressing the knowledge gaps which continue to hinder vaccine development for difficult pathogens and for the formation of new scientific paradigms which will inform the development of the next generation of vaccines.
These changes are described as immunosenescence and represent an issue of growing global concern for the maintenance of a healthy aging population. The current thinking is that in advanced age, the differentiation of haematopoietic stem cells into lymphoid and myeloid precursors skews in the direction of the latter, leading to fewer lymphocytes in the circulation, the causes of which are reviewed elsewhere The result is an immune system that is more vulnerable to infection with certain pathogens but which is also less responsive to immunisation.
As mentioned earlier, the immunisation programme in the UK currently includes three vaccines for those aged 65 years and above. Several other vaccines from the immunisation schedule have been studied in this age group but of these, only the TDaP vaccine induces a protective immune response comparable to that induced when it is administered earlier in life While the trivalent influenza vaccine, pneumococcal conjugate vaccine and herpes zoster vaccine are capable of mitigating their respective diseases to varying degrees, they do not induce a satisfactory immune response in the majority of the elderly population.
Some success has been achieved, for example, the zoster glycoprotein vaccine incorporating the AS01 B adjuvant system was recently shown to reduce the risk of herpes zoster infection in adults greater than 70 years of age in a Phase III clinical trial Greater understanding of the immunological factors that underlie the ageing adaptive response at the molecular and cellular level will be imperative to the development of restorative interventions that promote functional response to vaccination. Immunisation rates have been steadily rising over the last two decades, and global infant mortality appears to be on a steady decline.
With the considerable expense of new vaccines such as the human papillomavirus and pneumococcal vaccines, the disparity of access between socioeconomic regions will take considerably more funding to overcome, especially as more countries graduate from Gavi eligibility. Some of the current challenges to vaccine development have been summarised in this review, but rapid advances in the immunology that underpins vaccinology promises continuing progress in the development of novel, effective and safe vaccines.
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There are many new vaccines under development which target infections for which no vaccine currently exists and research into suitable antigens, live vectors and improved adjuvants continues to advance. The infrastructure put in place by these projects will create platforms for further research and development, ensuring that global health will continue to improve over future decades.
Volume 47 , Issue The full text of this article hosted at iucr. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username. European Journal of Immunology Volume 47, Issue Review Clinical Free Access.
Dylan Sheerin Corresponding Author E-mail address: dylan. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Introduction According to World Health Organisation WHO estimates, between 2 and 3 million deaths are averted worldwide on an annual basis as a result of childhood vaccination 1.
Figure 1 Open in figure viewer PowerPoint. Decline in infant mortality rate per live births between and A Decline in infant mortality in the UK. Regulatory approval and implementation policy Bringing a vaccine from discovery, through research and development to a licensed product is a lengthy and expensive process, taking an average of Figure 2 Open in figure viewer PowerPoint.
Summary of the steps required to take a vaccine to licensure. Once a vaccine fulfils the criteria required of it at the preclinical stage of development it must then pass through three phases of clinical trials before it acquires regulatory approval. A Phase IV clinical trial can be conducted after licensure to assess the impact that the vaccine has had on a population.
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The purpose of this collection is to review the past, understand the present, and look to the future of this field and the sociopolitical issues surrounding vaccinology and infectious disease. Through the publication of this collection, reflecting on both achievements and failures, Public Health Reviews aims to help students and teachers of public health to achieve a greater understanding of one of the most dynamic fields in public health and its future.
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