[Bacterial lysates: history and availability]. / Storia e diffusione dei lisati batterici utilizzati come "vaccini".

The use of bacterial lysates (BLs) can be traced back to the end of the nineteenth century, and they are currently available in several countries across all continents. Over the last few decades, BLs have been used, both in pediatric patients and in adults, mainly for the prevention and treatment of bacterial infections of the respiratory tract. BLs are produced from bacterial cultures that undergo cell lysis with two different methods: mechanical lysis and chemical lysis. The in vivo mechanism of action is still not fully understood, and the main hypotheses focus on mucosal immunity modulation. We searched PubMed for relevant papers on the use of BLs for the prevention and treatment of chronic obstructive pulmonary disease and recurrent respiratory infections both in adult and in pediatric patients. We retrieved 169 articles and after screening and selection, we analyzed 13 RCTs focusing on adult patients and 8 on pediatric patients. The outcomes assessed were mainly about the efficacy of BLs on exacerbations, hospitalizations, antibiotic treatment, fever, number of episodes and days of absence from work or school. Many aspects of BLs are still not well understood and the quality of available studies is not satisfactory; in order to place BLs within the scope of Public Health, further good quality studies are needed, keeping in mind the necessity to respond to the needs of patients for whom no alternative effective treatments are available.

The remarkable Dr Robertson.

Muriel Robertson (1883-1973) was a pioneering protozoologist who made a staggering number of important contributions to the fields of parasitology, bacteriology and immunology during her career, which spanned nearly 60 years. These contributions were all the more remarkable given the scientific and social times in which she worked. While Muriel is perhaps best known for her work on the life cycle and transmission of the African trypanosome, Trypanosoma brucei, which she carried out in Uganda at the height of a major Sleeping Sickness epidemic, her work on the Clostridia during the First and Second World Wars made significant contributions to the understanding of anaerobes and to the development of anti-toxoid vaccines, and her work on the immunology of Trichomonas foetus infections in cattle, carried out in collaboration with the veterinarian W. R. Kerr, resulted in changes in farming practices that very quickly eradicated trichomoniasis from cattle herds in Northern Ireland. The significance of her work was recognized with the award of Fellow of the Royal Society in 1947 and an Honorary Doctorate of Law from the University of Glasgow, where she had earlier studied, in 1948.

Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation--technological development issues.

This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.

Antibacterial vaccine research in 21st century: from inoculation to genomics approaches.

Vaccination is one of the safest and most cost-effective public health interventions, which save millions of lives annually. Thanks to all the genius pioneers of the field, we have already developed many effective vaccines. On the other hand, there are still many pathogens for which we do not yet have an effective or optimal vaccine, including malaria, HIV, and tuberculosis. In the 21(st) century, biological sciences are at the edge of a growing and fruitful genomics era, which provide many opportunities for vaccine research to have a better understanding of host-pathogen interactions, immune responses, targets and thus allow the scientists to design better vaccines. After the publication of the first bacterial genome of a pathogen, Haemophilus influenza, genomics technology revolutionized the field and created novel vaccine discovery approaches like reverse vaccinology, antigenome technology, surfome analysis, immunoproteomics, and genetics vaccinology to discover novel immunogenic antigens. This review is an attempt to briefly explain these methodologies and the history of their development since the beginning of the century.

USDA regulatory guidelines and practices for veterinary Leptospira vaccine potency testing.

Batch-release potency testing of leptospiral vaccines licensed by the United States Department of Agriculture (USDA) historically was conducted through animal vaccination-challenge models. The hamster vaccination-challenge assay was Codified in 1974 for bacterins containing Leptospira pomona, Leptospira icterohaemorrhagiae, and Leptospira canicola, and in 1975 for bacterins containing Leptospira grippotyphosa. In brief, 10 hamsters are vaccinated with a specified dilution of bacterin. After a holding period, the vaccinated hamsters, as well as nonvaccinated controls, are challenged with virulent Leptospira and observed for mortality. Eighty percent of vaccinated hamsters must survive in the face of a valid challenge. The high cost of the Codified tests, in terms of monetary expense and animal welfare, prompted the Center for Veterinary Biologics (CVB) to develop ELISA alternatives for them. Potency tests for other serogroups, such as Leptospira hardjo-bovis, that do not have Codified requirements for potency testing continue to be examined on a case-by-case basis.

Efficacy of whole-cell killed bacterial vaccines in preventing pneumonia and death during the 1918 influenza pandemic.

BACKGROUND: Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia. METHODS: We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic. RESULTS: A meta-analysis of 6 civilian studies of mixed killed bacterial vaccines containing pneumococci identified significant heterogeneity among studies and estimated VE at 34% (95% confidence interval [CI], 19%-47%) in preventing pneumonia and 42% (95% CI, 18%-59%) in reducing case fatality rates among patients with influenza, using random-effects models. Using fixed-effect models, the pooled VE from 3 military studies was 59% (95% CI, 43%-70%) for pneumonia and 70% (95% CI, 50%-82%) for case fatality. Military studies showed less heterogeneity and may provide more accurate results than civilian studies, given the potential biases in the included studies. Findings of 1 military study using hemolytic streptococci also suggested that there was significant protection. CONCLUSIONS: Despite significant methodological problems, the systematic biases in these studies do not exclude the possibilities that whole-cell inactivated pneumococcal vaccines may confer cross-protection to multiple pneumococcal serotypes and that bacterial vaccines may play a role in preventing influenza-associated pneumonia.

Sir Arnold Theiler and the discovery of anaplasmosis: a centennial perspective.

Sir Arnold Theiler's research in 1908/09 led to the discovery of the first rickettsial pathogen, Anaplasma marginale, and set the stage for his development and implementation of an effective live vaccine based on a less virulent strain, A. marginale ss. centrale. His 1910 report, describing A. marginale, is among the classic monographs in infectious disease research, presenting not only observations in exacting detail but also highlighting the deductive reasoning leading to association of a new pathogen with a specific disease. With a centennial perspective and both conceptual frameworks and molecular tools unimaginable in Theiler's time, the significance of several observations in the original report--cyclic bacteremia, strain superinfection, and taxonomic position--is now clear and highlight the broad applicability of key principles of pathogen biology.

Vaccines: the fourth century.

Vaccine development, which began with Edward Jenner's observations in the late 18th century, has entered its 4th century. From its beginnings, with the use of whole organisms that had been weakened or inactivated, to the modern-day use of genetic engineering, it has taken advantage of the tools discovered in other branches of microbiology. Numerous successful vaccines are in use, but the list of diseases for which vaccines do not exist is long. However, the multiplicity of strategies now available, discussed in this article, portends even more successful development of vaccines.

Chlamydia vaccine candidates and tools for chlamydial antigen discovery.

The failure of the inactivated Chlamydia-based vaccine trials in the 1960s has led researchers studying Chlamydia to take cautious and rational approaches to develop safe and effective chlamydial vaccines. Subsequent research efforts focused on three areas. The first is the analysis of the immunobiology of chlamydial infection in animal models, with supporting clinical studies, to identify the immune correlates of both protective immunity and pathological responses. Second, recent radical improvements in genomics, proteomics and associated technologies have assisted in the implementation of creative approaches to search for suitable vaccine candidates. Third, progress in the analysis of host response and adjuvanticity regulating both innate and adaptive immunity at the mucosal site of infection has led to progress in the design of optimal delivery and adjuvant systems for enhancing protective immunity. Considerable progress has been made in the first two areas but research efforts to better define the factors that regulate immunity at mucosal sites of infection and to develop strategies to boost protective immunity via immunomodulation, effective delivery systems and potent adjuvants, have remained elusive. In this article, we will summarize progress in these areas with a focus on chlamydial vaccine antigen discovery, and discuss future directions towards the development of a safe and effective chlamydial vaccine.

From rabbits to humans: the contributions of Dr. Theodore E. Woodward to tularemia research.

Tularemia is an endemic zoonotic infection caused by Francisella tularensis, which primarily causes infection in humans who have handled contaminated animal tissue or have been bitten by infected arthropods. Because of its ease of dispersion and transmission and its high degree of infectivity, F. tularensis is also considered to be a bioterrorism agent. Consequently, there is renewed interest in the development of safe, effective measures, such as vaccines, to prevent the morbidity and mortality associated with aerosol exposure to F. tularensis. Current efforts, however, are hampered by the lack of an animal model that faithfully reproduces human infection. Employing a model of "induced human infection" with aerosol administration of F. tularensis, Dr. Theodore E. Woodward and colleagues pioneered the clinical studies of tularemia vaccines that form the basis for current tularemia vaccine research.