Historical Advances in Structural and Molecular Biology and How They Impacted Vaccine Development.

Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major infectious diseases like polio, measles, mumps, and rubella, significantly blunted the impact of the COVID-19 pandemic, and prevented viral induced cancers such as cervical cancer caused by human papillomavirus. Recent technological advances, in genomics, structural biology, and human immunology have transformed vaccine development, enabling new technologies such as mRNA vaccines to greatly accelerate development of new and improved vaccines. In this review, we briefly highlight the history of vaccine development, and provide examples of where advances in genomics and structural biology, paved the way for development of vaccines for bacterial and viral diseases.

BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases.

First administered to a human subject as a tuberculosis (TB) vaccine on July 18, 1921, Bacillus Calmette-Guérin (BCG) has a long history of use for the prevention of TB and later the immunotherapy of bladder cancer. For TB prevention, BCG is given to infants born globally across over 180 countries and has been in use since the late 1920s. With about 352 million BCG doses procured annually and tens of billions of doses having been administered over the past century, it is estimated to be the most widely used vaccine in human history. While its roles for TB prevention and bladder cancer immunotherapy are widely appreciated, over the past century, BCG has been also studied for nontraditional purposes, which include (a) prevention of viral infections and nontuberculous mycobacterial infections, (b) cancer immunotherapy aside from bladder cancer, and (c) immunologic diseases, including multiple sclerosis, type 1 diabetes, and atopic diseases. The basis for these heterologous effects lies in the ability of BCG to alter immunologic set points via heterologous T cell immunity, as well as epigenetic and metabolomic changes in innate immune cells, a process called "trained immunity." In this Review, we provide an overview of what is known regarding the trained immunity mechanism of heterologous protection, and we describe the current knowledge base for these nontraditional uses of BCG.

A Narrative Review of Pediatric Nontraumatic Spinal Cord Dysfunction.

This article provides a narrative review of seven key issues relevant to pediatric onset of spinal cord damage not due to trauma, or spinal cord dysfunction (SCDys). The first topic discussed is terminology issues. There is no internationally accepted term for spinal cord damage not due to trauma. The implications of this terminology issue and an approach to addressing this are discussed. Second, a brief history of SCDys is presented, focusing on conditions relevant to pediatrics. Third, the classification of SCDys is outlined, based on the International Spinal Cord Injury Data Sets for Non-Traumatic Spinal Cord Injury. Following this, a summary is given of the epidemiology of pediatric SCDys, primarily focused on the incidence, prevalence, and etiology, with a comparison to traumatic spinal cord injury. Next, important clinical rehabilitation principles unique to children with SCDys are highlighted. Then important prevention opportunities for SCDys in children are discussed. Finally, trends, challenges, and opportunities regarding research in SCDys are mentioned.

Comprehensive real-time epidemiological data from respiratory infections in Finland between 2010 and 2014 obtained from an automated and multianalyte mariPOC® respiratory pathogen test.

Respiratory viruses cause seasonal epidemics every year. Several respiratory pathogens are circulating simultaneously and typical symptoms of different respiratory infections are alike, meaning it is challenging to identify and diagnose different respiratory pathogens based on symptoms alone. mariPOC® is an automated, multianalyte antigen test which allows the rapid detection of nine respiratory infection pathogens [influenza A and B viruses, respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, parainfluenza 1-3 viruses and pneumococci] from a single nasopharyngeal swab or aspirate samples, and, in addition, can be linked to laboratory information systems. During the study period from November 2010 to June 2014, a total of 22,485 multianalyte respi tests were performed in the 14 participating laboratories in Finland and, in total, 6897 positive analyte results were recorded. Of the tested samples, 25 % were positive for one respiratory pathogen, with RSV (9.8 %) and influenza A virus (7.2 %) being the most common findings, and 0.65 % of the samples were multivirus-positive. Only small geographical variations in seasonal epidemics occurred. Our results show that the mariPOC® multianalyte respi test allows simultaneous detection of several respiratory pathogens in real time. The results are reliable and give the clinician a picture of the current epidemiological situation, thus minimising guesswork.

[Sixty years ago, cell cultures finally permitted the poliomyelitis virus to multiply easily]. / Il y a 60 ans (1949), les cultures cellulaires permettaient enfin de multiplier aisément les virus de la poliomyélite.

In 1949, three American virologists, John F. Enders, Thomas H. Weller and Frederick C. Robbins, from the Harvard Medical Scholl and working at the Children's Medical Centre, Boston, Mass., have provoked a true revolution in Virology. Here, they have succeeded in readily multiplying the three poliomyelitis viruses in vitro, in non-nervous cells cultures. A few years afterwards (1954), they were collectively honoured by the Nobel Prize of Physiology and Medicine. This discovery not only has quickly led to the production of efficient poliomyelitis vaccines (J. E. Salk, 1953; A. B. Sabin, 1955) but also has permitted to easily isolate a number of already known viruses (measles, rubella, mumps, herpes simplex and herpes zoster) or until then totally unknown viruses (adenovirus, echovirus, cytomegalovirus). These progresses have significantly contributed to improve diagnosis, sanitary surveillance and vaccinal prophylaxis of human and animal viral diseases. Moreover, the cells cultures techniques have also benefited to other domains of fundamental Biology, such as cellular biology, genetics, cancerology, biology of the reproduction and regenerative medicine as well.

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.

100 years of virology: from vitalism via molecular biology to genetic engineering.

The identification of the causative agent of tobacco mosaic disease as a novel pathogen by the Dutch microbiologist Beijerinck is now acknowledged as being the foundation of virology as a discipline distinct from bacteriology. However, as this was contrary to the prevailing theories of the time, it took many years for virology to become firmly established as a separate discipline. The history of virology illustrates how accepted concepts in science evolve by trial and error and the need for a balanced approach when manipulating natural systems.

Viral diseases and human evolution

The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effects on human progress. Recently emerged diseases causing massive pandemics (e.g., HIV-1 and HCV, dengue, etc.) are becoming formidable challenges, which may have a direct impact on the fate of our species