Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections.

Persistent viral infections causing serious diseases derive, primarily, from altered function of the immune system. Knowledge of the very complex composition and function of the innate and adaptive branches of the immune system is essential to understanding persistent infection. The best solution to the problem of persistent infection is by prevention using prophylactic vaccines.

Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus.

Viral hepatitis B is an enigmatic disease in which the host's own immune response to persistent viral infection may bring about host destruction through antiviral inflammatory responses which might otherwise present as a benign or inapparent disease. The simple solution to the hepatitis B problem is by immunoprophylaxis using the vaccine licensed in 1981, which prevents both infection and the late sequelae of liver cirrhosis and hepatocarcinoma. Immunotherapeutic vaccines against persistent hepatitis B infection have not been successful and new explorations are being directed to therapies which include antisense, ribozymes, gene silencing by RNA interference (RNAi) and aptamer approaches.

Personal reflections on twentieth century vaccinology.

The science of vaccinology was created in the late 18th and 19th centuries by "giants" of the time including Jenner, Pasteur, Koch, von Behring, Ehrlich and Lister. Relatively little technologic advance was made in the period leading to World War II except for yellow fever and influenza vaccines. Support for war efforts fueled developments which led to the modern era of vaccines of 1950 onwards.

Overview of the needs and realities for developing new and improved vaccines in the 21st century.

The science of present day vaccinology is based on the pioneering discoveries of the late 18th and late 19th centuries and the technologic breakthroughs of the past 60 years. The driving force for the development of new vaccines resides in technologic feasibility, public need and economic incentive for translating the basic knowledge into a product. Past efforts by government to define which particular vaccines to develop were mostly irrelevant to the realistic choices which were made.

Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.

Influenza A is a viral disease of global dimension, presenting with high morbidity and mortality in annual epidemics, and in pandemics which are of infrequent occurrence but which have very high attack rates. Influenza probes reveal a continuing battle for survival between host and parasite in which the host population updates the specificity of its pool of humoral immunity by contact with and response to infection with the most recent viruses which possess altered antigenic specificity in their hemagglutinin (HA) ligand. HA ligand binds the virus to the cell to bring about infection.

Overview: cause and prevention in biowarfare and bioterrorism.

Bioweaponry is rooted in the ancient past. It became a science in the early 20th century following the breakthrough discoveries in microbiology and immunology of the late 1800s. The 20th century, with its major and minor wars, saw the research and development of biological weapons capable of immense destruction of life, which were used both by nations in preparation for military warfare and by individuals who engage in asymmetric warfare.

Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications.

Measles is one of the most important diseases of mankind, which is so highly contagious and evokes such persistent immunity that the virus cannot be sustained in a population of less than about 500,000 persons. The first of the licensed live virus vaccines against measles was developed empirically and was approved in 1963. It provides high level and lasting immunity and is a paradigm for solving major medical problems without really understanding them.

Overview of the pathogenesis, prophylaxis and therapeusis of viral hepatitis B, with focus on reduction to practical applications.

Hepatitis B is the most important of several hepatitis viruses of man because of the number of cases of the disease and the frequent occurrence of persistent infection that may lead to cirrhosis and cancer of the liver. The pathology of hepatitis B infection results mainly from the self-destructive cytotoxic T cell response of the host. This may be modulated by soluble pre-core e antigen of the virus that induces immune tolerance and by cytokines elaborated by cytotoxic T cells, which suppress viral replication in the infected cell.

Overview of vaccinology with special reference to papillomavirus vaccines.

Viruses that belong to six different families are a significant cause for neoplasia in man and animals. Among them are the Papillomaviruses that cause uterine cervical cancer in women. Efforts to develop prophylactic vaccines against viruses that cause cancer are now a major research engagement.

Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines.

Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early twentieth centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and Rickettsiae in vitro for vaccines.

International biological standardization in historic and contemporary perspective.

Recounting the origination and development of the concepts and institutions to foster and control new and existing biological products is a fertile subject for historical review. It describes what was a necessary and functional activity that needed to be brought into being. The earliest examples of biologicals regulation were created by the eighteenth century inventors themselves and became progressively institutionalized by the creation of national control authorities which increased in number and sophistication during the past century.

Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology.

The sciences of vaccinology and of immunology were created just two centuries ago by Jenner's studies of prevention of smallpox by inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th and early 20th centuries biomedical sciences. The period from 1930 to 1950 was a transitional era with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines.

The business of science and the science of business in the quest for an AIDS vaccine.

This paper simplifies and encapsulates the past, present and future for developing vaccines, especially against AIDS. Needed technical information and how it can best be obtained are delineated. The views are my own and may not be shared by others.

Overview of viruses, cancer, and vaccines in concept and in reality.

Cancer is a consequence of malfunction of the replicative cell cycle caused by acquisition of independence from proliferative and restrictive controls in the process. Such alteration may be driven by unrepaired mutations in proto-oncogenes and anti-oncogenes or by genetic insults of environmental, infectious, or spontaneous origin. The consequence of mutations may be reflected at any of a number of locations in the transductive pathways from receptor to nucleus which upset normal homeostatic balance between the opposing forces for promotion or restraint of cell proliferation.

Vaccines, human experimentation, and ethics in evolutionary perspective.

Clinical testing of unlicensed biological products is woven into issues of ethics and technology that reflect the state of the art. Materials for human testing must be of best possible quality and content, and must be safe. Testing of vaccines demands fulfillment of three ethical principles established since World War II.

Discovery of simian virus 40 (SV40) and its relationship to poliomyelitis virus vaccines.

Simian Virus 40 (SV40) was discovered in 1959 as a covert contaminant of poliovirus vaccines prepared using Macacus monkey renal cell cultures. This inapparent polyoma virus of monkeys was detected using Cercopithecus renal cell cultures and was eliminated from poliovaccines. There has been no evidence to implicate SV40 virus of vaccine origin in long- or short-term consequences in human subjects.

A simplified vaccinologists' vaccinology and the pursuit of a vaccine against AIDS.

Vaccinology is the science and engineering of developing vaccines to prevent infectious diseases. Guidelines come from knowledge of pathogenesis and from successful past vaccines. The vaccine enterprise relies on the evolution of appropriate science and technology.

Overview: practical insights from comparative immunology and pathogenesis of AIDS, hepatitis B, and measles for developing an HIV vaccine.

Combined effects of viral mutation, beneficial and adverse host immune responses, and alterations in immune function strongly fashion the pathogenesis and outcome of HIV infection. Understanding HIV can be aided by understanding hepatitis B and measles. Clinical remission and exacerbation in persistent hepatitis B virus infection is determined by the triad of viral mutation, induction of anergy, and host immune responses.