A century of innovation in vaccines

Surveying a century of vaccinology, the author sifts through three discrete eras and briefly examines some of the major factors accelerating and constraining the process of innovation. From the 1890 s through the 1930 s, most of the expectations generated by the scientific networks of the late nineteenth century were unfulfilled. During the next forty years, however, vaccinology experienced an astonishing era of innovation in vaccine discovery, development, and distribution. This golden age was followed, however, by the great paradox of our times: while the scientific opportunities have never been greater, there have been and continue to be serious threats to the viability of the three sets of institutions in the networks sustaining vaccine innovation.     

Perspectives on advancing preventative medicine through vaccinology at the comparative veterinary, human and conservation medicine interface: not missing the opportunities

Vaccination has historically and remains one of the most cost-effective and safest forms of medicine today. Along with basic understanding of germ theory and sanitation, vaccination, over the past 50 years, has transformed lives and economies in both rich and poor countries by its direct impact on human and animal life--resulting in the eradication of small pox, huge reductions in the burden of previously common human and animal diseases such as polio, typhoid, measles in human medicine and contagious bovine pleuropneumonia, foot-and-mouth disease, screwworm and hog cholera and the verge of eradicating brucellosis, tuberculosis, and pseudorabies in veterinary medicine. In addition vaccination along with other animal production changes has provided the ability to produce otherwise unaffordable animal protein and animal health worldwide. The landscape however on which vaccinology was discovered and applied over the past 200 years, even in the past 10 years has and is undergoing continuous change. For vaccination as a public health tool to have its greatest impacts in human and veterinary medicine, these great medical sciences will have to come together, policy-relevant science for sustainable conservation in developing and developed countries needs to become the norm and address poverty (including lack of basic health care) in communities affected by conservation, and to consider costs and benefits (perceived or not) affecting the well-being of all stakeholders, from the local to the multinational. The need to return to and/or develop new education-based models for turning the tide from the heavily return-on-investment therapeutic era of the last century into one where the investment into the preventative sciences and medicine lead to sustainable cultural and cost-effective public health and economic changes of the future is never more evident than today. The new complex problems of the new millennium will require new educational models that train para- and professional people for thinking and solving complex inter-related biological, ecological, public-, political/economic problems. The single profession that is best positioned to impact vaccinology is Veterinary Medicine. It's melding with human medicine and their role in future comparative and conservation-based programs will be critical to the successful application of vaccines into the 21st century.     

Lessons learned in the analysis of high-dimensional data in vaccinomics

The field of vaccinology is increasingly moving toward the generation, analysis, and modeling of extremely large and complex high-dimensional datasets. We have used data such as these in the development and advancement of the field of vaccinomics to enable prediction of vaccine responses and to develop new vaccine candidates. However, the application of systems biology to what has been termed “big data,” or “high-dimensional data,” is not without significant challenges—chief among them a paucity of gold standard analysis and modeling paradigms with which to interpret the data. In this article, we relate some of the lessons we have learned over the last decade of working with high-dimensional, high-throughput data as applied to the field of vaccinomics. The value of such efforts, however, is ultimately to better understand the immune mechanisms by which protective and non-protective responses to vaccines are generated, and to use this information to support a personalized vaccinology approach in creating better, and safer, vaccines for the public health.     

Systems vaccinology: Enabling rational vaccine design with systems biological approaches

Vaccines have drastically reduced the mortality and morbidity of many diseases. However, vaccines have historically been developed empirically, and recent development of vaccines against current pandemics such as HIV and malaria has been met with difficulty. The advent of high-throughput technologies, coupled with systems biological methods of data analysis, has enabled researchers to interrogate the entire complement of a variety of molecular components within cells, and characterize the myriad interactions among them in order to model and understand the behavior of the system as a whole. In the context of vaccinology, these tools permit exploration of the molecular mechanisms by which vaccines induce protective immune responses. Here we review the recent advances, challenges, and potential of systems biological approaches in vaccinology. If the challenges facing this developing field can be overcome, systems vaccinology promises to empower the identification of early predictive signatures of vaccine response, as well as novel and robust correlates of protection from infection. Such discoveries, along with the improved understanding of immune responses to vaccination they impart, will play an instrumental role in development of the next generation of rationally designed vaccines.     

Human vaccine research in the European Union

The use of vaccines is saving millions of lives every year across the globe, but a number of important diseases such as HIV/AIDS, malaria, TB and hepatitis C continue to frustrate attempts to produce effective vaccines against them. Confronting these challenges will require new approaches and increased research efforts by the scientific community. The Sixth Framework Programme (FP6; 2002–2006) of the European Commission (EC) has been an important catalyst in this direction by allocating a financial contribution of more than EUR 210 million to a wide variety of vaccine research activities, ranging from basic vaccinology, translational research to clinical application of vaccines. Taken together, around 581 research groups from 52 countries are participating in the vaccine activities of FP6. This impressive number signals a new spirit of collaborative research, which will facilitate the exploitation of the immense possibilities in modern vaccinology.     

The Second International Scientific Symposium on Tea & Human Health, September 14th, 1998

It is fascinating to reflect that tea, the world's most widely consumed beverage next to water, began in Chinese antiquity not as a beverage but as a medicine. Several millennia later, modern scientific research is confirming that such ancient intuition has relevance to contemporary health concerns including cancer, heart disease, and antibiotic-resistant bacteria. The timeliness of this message as the 20th century concludes could not be better. The importance of a balanced diet has been recognized and studied throughout this century. The concept that we are what we eat has become a part of popular culture. If tea's health message, which future scientific research will continue to articulate, is creatively presented and embraces the romantic image that tea affords the industry, there is every reason to expect a rebirth and reinvigoration of this ancient beverage as a new millennium commences.     

Why is evidence-based medicine so harsh on vaccines? An exploration of the method and its natural biases

Vaccines have been hailed as one of the greatest success stories of public health in the 20th century. The 20th century also produced a call for evidence-based medicine (EBM) with applications inclusive of preventive health. Since then, several major EBM analyses have called into question vaccine practices well-accepted by physicians, public health officials, and even the lay public. For example, while counter to existing studies and policies, EBM analyses have concluded that data are lacking to support influenza vaccination of healthcare workers to prevent flu complications among the elderly. In this review, we examine the criticisms and consider the shortcomings in the field of vaccinology as well as in the methodology of evidence-based medicine.     

Centenary of the Health Council of the Netherlands. IV. Infectious diseases

Many advisory reports of the Health Council of the Netherlands in the past century have dealt, directly or indirectly, with infectious diseases. One example is vaccination against smallpox. At the start of the last century, advice on this subject was important: initially, vaccination was compulsory by law, but people became increasingly aware of the associated side effects. A second example is immunisation against acute anterior poliomyelitis, which became a reality during the fifties. The advice also contained a discussion of which vaccine should be chosen: the inactivated 'dead' (Salk) form or the attenuated 'live' form (Sabin). Due to sound national organisation and associated logistics, a high level of vaccination was (and still is) achieved and the clinical disease known as polio disappeared from the Netherlands. Food-borne infections form the third example. The effect of the advice published by the Council on this subject (from 1960 onwards) has been limited, for a large part due to the significant economic consequences of the proposals for beef farming. The developments in the field of infectious diseases, immunology and vaccinology, together with social developments make it likely that in the coming years the Council will also frequently be asked for advice in the field of infectious diseases and the fight against them.     

Vaccines in historic evolution and perspective: a narrative of vaccine discoveries

The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early twentieth centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and Rickettsiae in vitro for vaccines. Modern era vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology and immunology, which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine.The present paper was presented as a lecture given(1) on August 30, 1999 and recounts, by invitation, more than five-and-half decades of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references [Hilleman MR. Six decades of vaccine development - a personal history. Nat. Med. 1998;4 (Vaccine Suppl.): 507-14] and [Hilleman MR. Personal historical chronicle of six decades of basic and applied research in virology, immunology and vaccinology. Immunol. Rev. (in press)]. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.     

Vaccinology: past achievements,present roadblocks and future promises

Of all the branches of modern medicine, vaccinology can claim to be the one that has contributed most to the relief of human misery and the spectacular increase in life expectancy in the last two centuries. It is the only science that has eradicated an infectious disease-smallpox-responsible for 8-20% of all deaths in several European countries in the 18th century. Other disabling and lethal diseases, like poliomyelitis and measles, are targeted for eradication. Currently, it is estimated that immunization saves the lives of 3 million children a year but 2 million more lives could be saved by existing vaccines. The success of vaccines in controlling and eliminating diseases has, paradoxically, been the cause of a revival of the anti-vaccination movement which in the absence, in developed countries, of many erstwhile common infectious diseases such as diphtheria, tetanus, polio, pertussis, measles, rubella and mumps has come to believe that vaccination is not only no longer necessary but is even dangerous. This is because it accepts, as "reactions", any untoward health event that occurs after administration of a vaccine. Most vaccine "reactions", therefore, appear to be more frequent than vaccine-preventable diseases. Public Health Authorities, aware of the great value of vaccines to society, are facing an uphill battle to get them accepted by a growing proportion of so-called educated minorities, thus endangering disease elimination. Other developments, in the last two decades, that have hampered vaccine usage have been the exploding costs of research, development and manufacture of new vaccines and the emphasis still placed on therapy in preference to prevention in medicine. This has led to the erroneous perception that vaccines are expensive although they are, in most cases, more cost-effective than the popular wait-see-treat approach. A favorable trend for vaccinology has been fueled by recent major breakthroughs in the sciences of immunology, molecular biology, genomics, proteomics, physico-chemistry and computers that promise a bright future for prevention, not only of acute infectious diseases, but also treatment of conditions like chronic infections, allergy, auto-immune diseases and cancer where some malfunctioning of the immune system is thought to play a part. Vaccines are being made more user-friendly by the development of combined vaccines and less painful and invasive inoculation techniques than the traditional syringe and needle. Recent new initiatives, like the Global Alliance on Vaccines and Immunization (GAVI),which are gathering new sources of funding for vaccination, should be beneficial for vaccinology.     

Development, dissemination and effectiveness of eugenic (racial public health) ideas in the abuse of the prevention concept in medicine

The scientific social hygiene and the eugenics (racial hygiene) based on biologistical concepts nearly simultaneously developed by the turn from 19th to 20th century. Whereas the prophylaxis has been a centralized social-hygienic request, the eugenics has been orientated on the transfer of the principle of selection and the regulations of the human procreation. The intermixture of partial aspects of both these concepts by uptake of eugenic ideas into social-hygienic samples and the declaration of the eugenics to be the "generative prophylaxis" or "hygiene of procreation" during the first third of the 20th century caused a temporary abuse of the term prophylaxis in the medicine. The modern efforts at a genetic prophylaxis differ by their exact and individual performance and the principle of an absolute voluntariness from eugenic conceptions of any provenance. There term eugenics has for objective, ethical and historical reasons no longer its basis of existence to characterize this purpose of the medicine.     

Rehabilitation of the concept of neurosis

The use of the term "neurosis" has been gradually pushed out form the medical literature and from the everyday practice since the eighties of the last century. Instead, the categories of DSM-III, and its new versions, and those of the ICD-10 have become commonly used. The author analyses the advantages and drawbacks of this radical change. He points out that it is not merely the problem of the medical profession. Transformation of the way of diagnostic thinking has been put into a broader social and cultural context. The expression "deconstruction" describes appropriately the process when comprehensive, entire categories resign to small sliced parts of reality. The deconstruction recalls the "Universalia-dispute" of the Middle Ages, namely the question whether the general concepts have real existence, and to what extent. The term "neurosis" as a comprehensive category, which is characteristic of many patients, it has a heuristic value if it is filled up with new contents (anthropology, ontology).     

Advanced vaccinology training globally: Update and impact of the COVID-19 crisis

The rapid development of innovations and new technologies, the focus on the life-course approach to immunization and equity, and the prevalent hesitancy towards vaccines requires immunization staff to be well-trained and updated regularly in order to deliver quality immunization services to the public. The need for advanced vaccinology training is therefore paramount. In preparation for a second Global Workshop on Advanced Vaccinology Training that took place in March 2022, this paper presents the results of a survey aiming to provide a thorough update of a landscape analysis on advanced vaccinology courses conducted in 2018 and a look at the impact of the COVID-19 crisis. Thirty-three course organizers responded to a survey to provide information on their respective course. Of those, 17 courses are short courses, 11 post-graduate courses and 5 are Master level courses. Most courses are organized on an annual basis. Even though some courses were not sustained overtime, the number of courses has been increasing during the last few years, and at least one vaccinology course is now being offered in each WHO region. Although the training capacity has increased tremendously, the need still exceeds the capacity and many courses have way more applicants than they can select. The most frequent challenges reported included sustainable funding and identifying faculty. The COVID-19 pandemic impacted the delivery of several vaccinology courses, which have been postponed or reformatted to an online or hybrid training event. An e-portal of the global collaboration has been established to facilitate communication between the different courses and to assist future course participants to identify the most suitable course for their needs.     

The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens

Neisseria meningitidis is a major cause of endemic cases and epidemics of meningitis and devastating septicemia. Although effective vaccines exist for several serogroups of pathogenic N. meningitidis, conventional vaccinology approaches have failed to provide a universal solution for serogroup B (MenB) which consequently remains an important burden of disease worldwide. The advent of whole-genome sequencing changed the approach to vaccine development, enabling the identification of potential vaccine candidates starting directly with the genomic information, with a process named reverse vaccinology. The application of reverse vaccinology to MenB allowed the identification of new protein antigens able to induce bactericidal antibodies. Three highly immunogenic antigens (fHbp, NadA and NHBA) were combined with outer membrane vesicles and formulated for human use in a multicomponent vaccine, named 4CMenB. This is the first MenB vaccine based on recombinant proteins able to elicit a robust bactericidal immune response in adults, adolescents and infants against a broad range of serogroup B isolates. This review describes the successful story of the development of the 4CMenB vaccine, with particular emphasis on the functional, immunological and structural characterization of the protein antigens included in the vaccine.     

Psychology and health: contributions of psychology to the improvement of health and health care

Psychology as both a science and a profession has been closely identified with other disciplines in the broad field of health since the turn of the present century. Recent advances in health care have reinforced the growing belief that the promotion of health and the prevention and treatment of illness can be greatly enhanced by incorporating the scientific findings and modern techniques of psychology into everyday practices. This review outlines the contributions of psychology to health care throughout the world; only some of the most timely and relevant issues are mentioned, together with examples of current work in the field. After an introductory overview, special attention is given to each of the major areas within the broad field of health care where psychological applications have been particularly useful.     

媒介生物学和防治研究展望

媒介生物学和防治研究作为预防医学的一个重要组成部分,近十年来国内外都有较大进展。展望九十年代,媒介防治将发展为城市建设的内容之一。清除蚊、蝇、鼠等媒介已成为文明城市标志之一。媒介生物学和防治也正发展为以医学昆虫学为基础,与流行病学、微生物学、寄生虫学、动物生态学密切结合的综合学科。随着防治理论和方法的提高,媒介生态学研究更需深化。这方面的重点将是媒介种群动态的研究,利用现代计算技术,以数学模型模拟这种动态,作为虫媒病流行和媒介发生的监测和预测预报的依据。同时,组成综合媒介治理的各项手段,也将由于对它们认识的提高而得以进一步发挥其作用。我们可以期望,到本世纪末,我国一些重要媒介的生态学研究将赶上国际八十年代的水平,而在媒介防治实施方面,则可处于更先进的地位。