Inactivation of SAM-methyltransferase is the mechanism of attenuation of a historic louse borne typhus vaccine strain

Louse borne typhus (also called epidemic typhus) was one of man's major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. The fear of a bioterrorist attack using the etiologic agent of typhus, Rickettsia prowazekii, was a reality. An attenuated typhus vaccine, R. prowazekii Madrid E strain, was observed to revert to virulence as demonstrated by isolation of the virulent revertant Evir strain from animals which were inoculated with Madrid E strain. The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. We sequenced the genome of the virulent revertant Evir strain and compared its genome sequence with the genome sequences of its parental strain, Madrid E. We found that only a single nucleotide in the entire genome was different between the vaccine strain Madrid E and its virulent revertant strain Evir. The mutation is a single nucleotide insertion in the methyltransferase gene (also known as PR028) in the vaccine strain that inactivated the gene. We also confirmed that the vaccine strain E did not cause fever in guinea pigs and the virulent revertant strain Evir caused fever in guinea pigs. We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. This suggested that an irreversible insertion or deletion mutation in the methyl transferase gene of R. prowazekii is required for Madrid E to be considered a safe vaccine

Macaque models of human infectious disease.

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease

Wanted, an Anthrax vaccine: Dead or Alive?

It has been more than 100 years since the realization that microbes are capable of causing disease. In that time, we have learned a great deal as to how each organism has adapted to the immune system so as to avoid elimination. As well, we have also learned an immense amount since Louis Pasteur first proposed that the solution to infectious diseases was to culture the microbes and attenuate their virulence, so as to use them as vaccines. From the optimism and promise of the 19(th )century and immunization as the ultimate answer to the invasion by the microbial world, to the scientific realities of the 21(st )century, it is of interest to retrace the steps of the earliest microbiologists cum immunologists, to realize how far we've come, as well as how far we yet have to go. This editorial focuses on the history of anthrax as a microbial disease, and the earliest efforts at producing a vaccine for its prevention

Post vaccinal temporary sensorineural hearing loss

In our systematic research we identified four studies concerning the onset of neurological adverse events following vaccination and two excluding this association. A 33-year-old Italian man, belonging to the Italian Army was hospitalized because he suffered from vertigo, nausea and sudden right hearing loss not classified (NDD), that set in 24 h after the administration of tetanus-diphtheria and meningococcal vaccines. Some neurological events arising after vaccination are very difficult to treat. In our case, the functional recovery on low and medium frequencies was possible about 6 months after the morbid event

Immunization against infectious disease 1968

This edition of Immunization Against Infectious Disease is a review of the status of infectious diseases important to the United States and for which there are effective immunizing agents. The depth of analysis, scope of coverage, and general level of detail will undoubtedly change with added insights and new sources of information. This edition, primarily covering data summarized through the 1968 calendar year, is addressed to the students of public health and medicine; it assesses for them not only achievements in control but also their obligations toward maintaining alertness to present and future needs.196

The Role of Scientific Discovery in the Establishment of the First Biological Weapons Programmes

YesThis report addresses the scientific and technological discoveries in the biological sciences that enabled the early interest in biological warfare to move from hurling infected corpses into enemy cities in ancient times, through use of small cultures of animal pathogens to sabotage enemy livestock in World War I, to the origins of organised military biological weapons (BW) programmes directed at humans, animals, and plants in the inter-war period. It builds on Dando¿s 1999 paper: The Impact of the Development of Modern Biology and Medicine on the Evolution of Offensive Biological Warfare Programs in the Twentieth Century.1 For the historical aspects of biological warfare programmes this report primarily draws from the Stockholm International Peace Research Institute volume: Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945.