109 results match your criteria: "Merck Institute for Therapeutic Research[Affiliation]"

Overview of vaccinology with special reference to papillomavirus vaccines.

J Clin Virol

October 2000

Merck Institute for Therapeutic Research, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA.

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.

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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.

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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.

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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.

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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.

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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.

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

Recent Results Cancer Res

March 1999

Merck Institute for Therapeutic Research, Merck Research Laboratories, West Point, PA 19486, USA.

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.

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Vaccines, human experimentation, and ethics in evolutionary perspective.

Dev Biol Stand

March 1999

Merck Institute for Therapeutic Research, Merck Research Laboratories, West Point, PA 19486, USA.

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.

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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.

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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.

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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.

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DNA vectors. Precedents and safety.

Ann N Y Acad Sci

November 1995

Merck Institute for Therapeutic Research, Merck Research Laboratories (WP 53C-350), West Point, Pennsylvania 19486, USA.

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Comparative biology and pathogenesis of AIDS and hepatitis B viruses: related but different.

AIDS Res Hum Retroviruses

November 1994

Merck Institute for Therapeutic Research, Merck Research Laboratories, West Point, Pennsylvania 19486.

AIDS (HIV) and hepatitis B viruses are remarkably similar in their sharing of reverse transcription, in their ancestral origins and common genetic elements, and in their modes of transmission. Both are hypermutable and exist as quasispecies due primarily to errors in reverse transcription, though there is severe restriction in the replicative competence of most hepatitis B mutants. They differ in the lack of an integrase in hepatitis B virus and in their pathogenesis in the infected host.

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Current approaches to the prevention and control of AIDS by vaccines and by chemotherapy have failed to provide satisfactory solutions to this important medical problem and have failed, in addition, to provide definitive guidelines for future research endeavor. Vaccine research must and will continue but it is possible that a safe and effective vaccine may never be developed and it may be timely to explore, in addition, alternative means for immunological intervention in AIDS. Both immunoprophylactic and immunotherapeutic efforts might be assisted by manipulating the T helper 1 (Th1) and T helper 2 (Th2) subsets of CD4+ T helper cells, which is therefore worthy of exploration.

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Recombinant vector vaccines in vaccinology.

Dev Biol Stand

December 1994

Merck Institute for Therapeutic Research, Merck Research Laboratories, West Point, PA.

The development of recombinant vector vaccines will be guided by nearly two centuries of research in vaccinology and immunology. Experimental vector vaccines may be of viral, bacterial or genetic composition and their acceptability will depend on safety, efficacy, and practicality as seen by the user, the developer, and the licensing authority. Recombinant vector vaccines will need to compete with alternative vaccine approaches and may find special use for non-propagable agents, immunization in early life, fertility control, and emerging infectious agents.

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Human hepatitis has been recognized since the dawn of recorded history, but proof of infectious etiology and delineation of hepatitis A (infectious hepatitis) from hepatitis B (serum hepatitis) were not established until the first half of the present century. Development of the present killed hepatitis A vaccine depended on a series of breakthrough discoveries made during the last 25 years. These were marmoset propagation (1967); definition of virus attributes (1974-1975); development of diagnostic tests and seroepidemiology (1974-1975); and the preparation and proof of efficacy of a prototype killed hepatitis A vaccine (1976).

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The interaction of iberiotoxin (IbTX) with the large-conductance calcium-activated potassium (maxi-K) channel was examined by measuring single-channel currents from maxi-K channels incorporated into planar lipid bilayers. Addition of nanomolar concentrations of IbTX to the external side of the channel produced long nonconducting silent periods, which were interrupted by periods of normal channel activity. The distributions of durations of blocked and unblocked periods were both described by single exponentials.

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