Vaccine Evolution and Its Application to Fight Modern Threats.

Before the development of the first vaccine, infectious diseases were a major cause of death around the globe with life expectancy estimated to be <50 years. Three measures have helped to drastically reduce the burden of infectious diseases but only vaccines have proven to be able to eradicate infectious agents. Herein, we describe new methodologies that have paved the way for what is currently known as modern vaccinology and the use of vaccines to tackle antimicrobial resistance, the biggest global threat of our time.

[About a note published in 1926 on a BCG vaccine trial in leprosy treatment]. / À propos d'une note de 1926 sur un essai du BCG dans le traitement de la lèpre.

By 1926, two French physicians working in Indochina, R. Pons and L. Chastel, have suggested to treat leprosy by subcutaneous injections of bacillus Calmette-Guerin. This treatment appeared efficient since the lepromatous lesions quickly regressed and the Hansen bacillus disappeared from the nasal mucus. These results were quickly confirmed by other authors. They were all more appreciated than, at this time, the Chaulmoogra oil and its products, the only available drugs, were poorly efficient against the disease. Nevertheless, although not a panacea, the BCG therapy allowed to relieve these unfortunate patients until the beginning of the 1950's when an effective treatment by sulfones was at length available.

Biomedical loopholes, distrusted state, and the politics of HIV/AIDS "cure" in Nigeria.

As socio-medical phenomena, epidemics are revealing of the cultures in which they are experienced. The HIV/AIDS epidemic in Africa exposes antecedent tensions between state and society, and, on a broader canvas, between the global north and south. As a contribution to the emerging literature on the social ramifications of HIV/AIDS, this article examines the saga of the Nigerian physician and immunologist, Dr Jeremiah Abalaka, who like other innovators in sub-Saharan Africa claims to have developed a curative HIV vaccine. Whilst articulating the social conditions that enabled Abalaka to thrive, the article explores the marked differences in the reaction to his "discovery" among state representatives, the scientific establishment, the general public, people living with HIV, and the media. Finally, the article valorizes the emergence of new actors in the African health sector, and the diversity of strategies used by ordinary people to achieve and maintain wellness.

An appreciation of Ralph Marvin Steinman (1943­2011).

Ralph Steinman, an editor at the Journal of Experimental Medicine since 1978, shared the 2011 Nobel Prize in Physiology or Medicine for his discovery of dendritic cells (DCs) and their role in immunity. Ralph never knew. He died of pancreatic cancer on September 30, 3 days before the Nobel announcement. Unaware of his death at the time of their announcement, the Nobel Committee made the unprecedented decision that his award would stand. Ralph was the consummate physician-scientist to the end. After his diagnosis, he actively participated in his 4.5 years of treatments, creating experimental therapies using his own DCs in conjunction with the therapies devised by his physicians, all the while traveling, lecturing, and most of all pursuing new investigations in his laboratory. For 38 years­from his discovery of DCs to his Nobel Prize­Ralph pioneered the criteria and methods used to identify, isolate, grow, and study DCs. He and his colleagues demonstrated that DCs are initiators of immunity and regulators of tolerance. In his most recent studies, Ralph was harnessing the specialized features of DCs to design improved vaccines. The following synopsis describes some of his seminal discoveries.

Unique human tumor antigens: immunobiology and use in clinical trials.

The individual, unique tumor Ags, which characterize each single tumor, were described 50 years ago in rodents but their molecular characterization was limited to few of them and obtained during the last 20 years. Here we summarize the evidence for the existence and the biological role of such Ags in human tumors, although such evidence was provided only during the last 10 years and by a limited number of studies, a fact leading to a misrepresentation of unique Ags in human tumor immunology. This was also due to the increasing knowledge on the shared, self-human tumor Ags, which have been extensively used as cancer vaccines. In this review, we highlight the biological and clinical importance of unique Ags and suggest how they could be used in clinical studies aimed at assessing their immunogenic and clinical potential both in active and adoptive immunotherapy of human tumors.

Vaccine therapy for HIV: a historical review of the treatment of infectious diseases by active specific immunization with microbe-derived antigens.

A review of the history of 'vaccine therapy' for infectious diseases is presented. The concept originated when Auzias-Turenne introduced 'syphilitic vaccination' or 'syphilization' as a treatment for syphilis in Paris in the mid-1800s; his clinical studies probably influenced Pasteur's successful rabies postexposure vaccine trials. Robert Koch in Berlin in the 1890s observed that inoculation of tuberculin into patients with tuberculosis induced an inflammatory response in affected tissues, and advocated 'tuberculin therapy'. Sir Almroth Wright in London in the early 20th century devised methods to measure changes in serum 'opsonizing' activity in response to therapeutic inoculations with microbe-derived vaccines. Since the advent of antibiotics, active specific immunization with microbe-derived antigens (vaccine therapy) has been largely forgotten as a strategy for treatment of infectious diseases. Advances in antigen production and in molecular immunology now permit new tactics to probe, analyse and selectively alter in vivo human immune responses to infectious microbes. Our recent demonstration that vaccine therapy can boost natural immunity to HIV in infected patients should rekindle interest in this approach.

Of postulates and peccadilloes: Robert Koch and vaccine (tuberculin) therapy for tuberculosis.

In August 1890, Robert Koch dramatically announced that he had discovered a cure for tuberculosis, and the world rejoiced. The miracle substance was subsequently revealed to be tuberculin, inoculated as a 'vaccine therapy'. However, within a matter of months his claims were disputed and debunked, and his reputation was grievously damaged. The nationalistic pressures, professional jealousies and pecuniary interests that drove Koch's premature announcement are reviewed here and discussed in a context relevant to the development of therapeutic vaccines for human immunodeficiency virus infections.