Smallpox vaccines: Past, present, and future

The global eradication of smallpox was a tremendous achievement made possible by the development of an effective vaccine. Routine vaccination of the general population is no longer recommended. However, stocks of variola virus, the causative agent of smallpox, still exist in 2 secure laboratories, and permanent disposal has been controversial. In addition, there is speculation that variola virus may exist outside of these 2 facilities, and there is a concern that the threat of smallpox will be used as a bioterrorist weapon. In 2002, this concern led to a vaccination campaign in US military and civilian healthcare workers and first responders. Although the historical live virus vaccine has proven efficacy, it also is associated with serious adverse events and rare fatal reactions, particularly in the setting of immunodeficiency and atopic eczema. In addition, this vaccine was historically produced using animal intermediaries in a process that was prone to contamination and not acceptable for current manufacturing standards. Development of alternative poxvirus vaccines is focused on replication-defective viruses, gene-based vectors, and subunit approaches to improve safety and immunogenicity. The conundrum is that in the absence of an intentional release of variola, efficacy evaluation of new candidate vaccines will be limited to animal model testing, which creates new challenges for the vaccine licensure process. Although motivated by the threat of bioterrorism, the hope is for new poxvirus vaccines to have their greatest utility against other pathogenic orthopoxviruses such as monkeypox and for the development of recombinant poxvirus-based vectors to treat and prevent other diseases.     

Molecular Diagnostics: Past,present, and future

Molecular diagnostics (MDx) is currently a clinical reality that has its roots deep in the study of gene function, structure, and regulation. The multitude of human mutations identified in the various genetic diseases can now he assayed in the clinical molecular diagnostics laboratory. The polymerase chain reaction (PCR) has facilitated the transition from the research to the clinical laboratory, however, many methods which scan and identify known mutations may not be applicable in a clinical environment. A few of these methods are discussed and one technology that is well suited for clinical use is suggested. Well-trained personnel, regulation of MDx laboratories, and automation are a few of the requirements that will carry us into the promising future of molecular diagnosis. © 1993 Wiley-Liss, Inc.     

Amyloid imaging: Past,present and future perspectives

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised by the gradual onset of dementia. The pathological hallmarks of the disease are Aβ amyloid plaques, and tau neurofibrillary tangles, along dendritic and synaptic loss and reactive gliosis.Functional and molecular neuroimaging techniques such as positron emission tomography (PET) using functional and molecular tracers, in conjuction with other Aβ and tau biomarkers in CSF, are proving valuable in the differential diagnosis of AD, as well as in establishing disease prognosis. With the advent of new therapeutic strategies, there has been an increasing application of these techniques for the determination of Aβ burden in vivo in the patient selection, evaluation of target engagement and assessment of the efficacy of therapeutic approaches aimed at reducing Aβ in the brain.     

Evolution of human lifespan: Past,future, and present

The only satisfactory general theory for understanding the biology of aging is that provided by evolutionary genetics. The central theoretical result of the evolutionary theory of aging is that aging is caused by a fall in the force of natural selection, beginning at the time of the onset of reproduction and continuing until the cessation of reproduction. This formal result has been tested using breeding experiments in which the force of natural selection is altered in replicated laboratory populations. As predicted by the evolutionary theory of aging, such experiments can readily postpone aging. A recent advance has been the discovery of late-life mortality plateaus in human and other populations. These can be predicted theoretically from the late-life plateau in the force of natural selection, when it remains at or near zero. It is virtually certain that human lifespan has substantially increased over its last few million years of evolution. Evolutionary theory can explain this increase in terms of decreased ecological vulnerability resulting from increased brain size. The immediate future of human evolution is unlikely to see extensive genetic increases in lifespan, given the experimental data on rates of change in lifespan with experimental populations. But, evolutionary research suggests that there are few fundamental biological barriers to the extension of human lifespan, only practical barriers. Am. J. Hum. Biol. 10:409–420, 1998. © 1998 Wiley-Liss, Inc.     

Past,present and future of cutaneous lymphomas

Primary cutaneous lymphomas represent a broad group of diseases with different clinical, histopathological, phenotypic, molecular, and prognostic features. All cutaneous lymphomas share the same tropism of neoplastic lymphocytes for the skin, but precise classification is paramount for proper management of the patients. Primary cutaneous lymphomas are classified according to the schemes proposed by the European Organization for Research and Treatment of Cancer (EORTC)-Cutaneous Lymphomas Task Force together with the World Health Organization (WHO) in 2005, and the WHO classification of 2008 with the 2016 update. The recognition of organ-based lymphomas, including cutaneous lymphomas, reflects a shift in the approach to lymphoproliferative disorders, and represents one of the major advances in the WHO classification of hematological tumors. Future studies should be aimed at shedding light on the many grey areas of cutaneous lymphomas (particularly the diagnosis and nomenclature of early mycosis fungoides and variants), and at gathering more data on the disorders that are still listed as provisional entities in the WHO classification.     

Vaccines and vaccine resistance: Past,present and future

BackgroundEdward Jenner, by any definition would be considered the father of vaccinology. His use of cow pox virus for vaccinating against small pox is the prime example of a live vaccine. Using a virus that has very low virulence for humans and therefore, fits the definition of attenuated. Hesitancy towards a vaccine of this type, much before the science of microbiology and immunology were established, would have been justifiable. In the first half of 20th century, large number of vaccines became available for childhood diseases with significant morbidity and mortality. Around the same time global travel and trade led to escalation in the widespread transmission of diseases caused by microbes.ObjectiveThe objective of this narrative is to offer a balanced view of science behind vaccines, their current status and advances expected in the near future. At the same time the various types of reactions from public at large towards vaccines over past decades are reviewed.ContentThis narrative provides a historical perspective of vaccine development, reviews mechanisms of vaccine induced protection, currently available vaccine technologies and vaccines. The focus is on newer vaccines including those utilizing viral vectors and gene based vaccines. Based on the times during which this narrative is being written, messenger RNA vaccines are discussed in detail.ConclusionThe content and review of literature offered in this review makes the impact of vaccines on human life clear. It is also to be accepted that resistance and hesitation towards vaccines is nothing new or limited to vaccines being used during the ongoing pandemic of Covid 19. The continued development of science and products of vaccinology is necessary for further impact on human life. The development of a strong public health infrastructure by nations around the world is the key to improve upon current efforts at public awareness, proactive interventions and appropriate vaccine utilization during all times. Preparedness for epidemics and pandemics would then become more and more efficient than currently in existence.     

Past,present, and future of anti-IgE biologics

About 20 years after the identification of immunoglobulin E (IgE) and its key role in allergic hypersensitivity reactions against normally harmless substances, scientists have started inventing strategies to block its pathophysiological activity in 1986. The initial concept of specific IgE targeting through the use of anti-IgE antibodies has gained a lot of momentum and within a few years independent research groups have reported successful generation of first murine monoclonal anti-IgE antibodies. Subsequent generation of optimized chimeric and humanized versions of these antibodies has paved the way for the development of therapeutic anti-IgE biologicals as we know them today. With omalizumab, there is currently still only one therapeutic anti-IgE antibody approved for the treatment of allergic conditions. Since its application is limited to the treatment of moderate-to-severe persistent asthma and chronic spontaneous urticaria, major efforts have been undertaken to develop alternative anti-IgE biologicals that could potentially be used in a broader spectrum of allergic diseases. Several new drug candidates have been generated and are currently assessed in pre-clinical studies or clinical trials. In this review, we highlight the molecular properties of past and present anti-IgE biologicals and suggest concepts that might improve treatment efficacy of future drug candidates.     

Past, present and future of the therapy of emphysema

Senile atrophic emphysema was for a long time a term used to describe the pulmonary structure of elderly people. Since emphysema occurs mostly in elderly people, it was understood as the premature occurrence of a more or less normal ageing process. Therefore, almost no therapy seemed to be possible. Later emphysema was thought to be the consequence of airway obstruction, where the narrowed bronchi behave as check valves, so that the trapped air leads to overinflation and rupture of the alveoli. Thus bronchodilators were tried in the prevention of emphysema. This concept was partially successful, but also without bronchial obstruction emphysema can develop and progress. Experiments by Gross suggested that emphysema is a self-digesting process in the course of inflammatory defence of the body. Thus the inflammatory process itself became the target of the therapy. Additional therapy was tried by teaching special types of breathing and by breathing exercises, but had rather small success. Today our interest is focused on the imbalance of oxidants and antioxidants as the main reason for the self-digesting process. We hope to correct this imbalance, but we must be careful not to block a useful defence mechanism of the body.     

High-frequency neural activity and human cognition: Past, present and possible future of intracranial EEG research

Human intracranial EEG (iEEG) recordings are primarily performed in epileptic patients for presurgical mapping. When patients perform cognitive tasks, iEEG signals reveal high-frequency neural activities (HFAs, between around 40Hz and 150Hz) with exquisite anatomical, functional and temporal specificity. Such HFAs were originally interpreted in the context of perceptual or motor binding, in line with animal studies on gamma-band ('40Hz') neural synchronization. Today, our understanding of HFA has evolved into a more general index of cortical processing: task-induced HFA reveals, with excellent spatial and time resolution, the participation of local neural ensembles in the task-at-hand, and perhaps the neural communication mechanisms allowing them to do so. This review promotes the claim that studying HFA with iEEG provides insights into the neural bases of cognition that cannot be derived as easily from other approaches, such as fMRI. We provide a series of examples supporting that claim, drawn from studies on memory, language and default-mode networks, and successful attempts of real-time functional mapping. These examples are followed by several guidelines for HFA research, intended for new groups interested by this approach. Overall, iEEG research on HFA should play an increasing role in cognitive neuroscience in humans, because it can be explicitly linked to basic research in animals. We conclude by discussing the future evolution of this field, which might expand that role even further, for instance through the use of multi-scale electrodes and the fusion of iEEG with MEG and fMRI.     

Past,present, and future of allergen immunotherapy vaccines

Allergen-specific immunotherapy (AIT) is an allergen-specific form of treatment for patients suffering from immunoglobulin E (IgE)-associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease-causing allergen with the goal to induce a protective immunity consisting of allergen-specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact. Major advantages of AIT over all other existing treatments for allergy are that AIT induces a long-lasting protection and prevents the progression of disease to severe manifestations. AIT is cost effective because it uses the patient´s own immune system for protection and potentially can be used as a preventive treatment. However, broad application of AIT is limited by mainly technical issues such as the quality of allergen preparations and the risk of inducing side effects which results in extremely cumbersome treatment schedules reducing patient´s compliance. In this article we review progress in AIT made from its beginning and provide an overview of the state of the art, the needs for further development, and possible technical solutions available through molecular allergology. Finally, we consider visions for AIT development towards prophylactic application.