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Biomedical subjects

M R Hilleman

Publications and source records attributed to M R Hilleman.

At least 19 recordsLinked to original sources
PubMed1992

Impediments, imponderables and alternatives in the attempt to develop an effective vaccine against AIDS.

A personal view is presented that current successful vaccines against 'ordinary' viruses do not provide the guidelines needed for development of effective vaccines against the 'extraordinary' viruses that cause AIDS. Present 'candidate' AIDS vaccines fail to recognize the special attributes that are needed to make them successful. There is an urgent need for intensive studies of pathogenesis to seek and find the clues needed for vaccine attack that are at present unknown. Also needed is a targeted Research and Development organization comprising a cadre of capable scientists of requisite disciplines in adequate facilities, dedicated solely to the development of a vaccine against AIDS. The urgency imposed by the AIDS pandemic merits a new dedication to targeted basic research discovery and an effectively concentrated and coordinated applied research initiative.

AIDS Vaccines↗
PubMed1992

The dilemma of AIDS vaccine and therapy. Possible clues from comparative pathogenesis with measles.

AIDS viruses, because of their unique properties, are extraordinary. Past successes achieved with vaccines against ordinary viruses do not provide the guidelines needed to develop successful vaccines against HIV. Neither vaccines nor drugs can be relied upon to provide an answer to AIDS. AIDS is a disease of immune dysfunction and destruction, and an alternative to prevention of infection or cure might lie with elimination of the clinical consequences of infection. This might find a basis in precise definition of its pathogenesis. The enormity of possible pathogenetic changes in HIV infection invites simplification, and might be aided by a search for clues among ordinary viruses in which there is a less complicated biology and spontaneous recovery from infection. Measles virus infection presents analogies to AIDS, especially in the induction of anergy and increased mortality, in the long term, from diseases other than measles as observed in children infected during early life. This was demonstrated recently in increased deaths, all causes, during a three-year period among infants who were given live measles virus vaccine of high infectivity titer during early infancy, sometimes in the presence of maternal antibody. AIDS and measles may be diseases of similar pathogenesis, but with the difference that AIDS immunopathology is progressive while that for measles is regressive.

AIDS Vaccines↗
PubMed1990

History, precedent, and progress in the development of mammalian cell culture systems for preparing vaccines: safety considerations revisited.

The use of cell substrates to propagate viruses or recombinant plasmids for vaccine productions has been the subject of long evolutionary conflict, primarily from the standpoint of product safety, and especially from the viewpoint of cancer induction. The present concern is for safety of vaccines made using transformed or neoplastic mammalian cells that may contain endogenous contaminating viruses or integrated gene sequences from oncogenic viruses. There is also concern for use of plasmid vectors employing promoter elements from oncogenic viruses. The principal concern for safety lies with retention of residual DNA in the vaccine, especially since induction of cancer is a single-cell phenomenon, and a single functional unit of foreign DNA integrated into the host cell genome might serve to induce cell transformation as a single event or part of a series of multifactorial events. Current proposed standards for vaccines would permit contamination with up to 100 pg of heterologous DNA per dose. This is equivalent to about 10(8) "functional lengths" of DNA. Total safety would seem to require complete absence of DNA from the product. While preparation of biologicals used to treat serious disease might demand the use of mammalian cells, this is not the situation with vaccines that are given prophylactically to persons who might be given equally efficacious vaccines produced in bacterial cells or in yeast that have attributes for greater safety. Careful assessment of safety and risk vs. benefit of continuous mammalian cell-produced vaccines should be made by technically expert scientists in the relevant disciplines and a consensus needs to be evolved in the scientific community at large.

Animals↗
PubMed1988

Hepatitis B and AIDS and the promise for their control by vaccines.

Human hepatitis B virus and human immunodeficiency virus (HIV), that causes AIDS, share attributes and possible evolutionary relationships. The specific requirements for inducing effective immunity against hepatitis B and HIV are discussed. Lessons learned in studies of hepatitis B and its vaccine may find application in creating a vaccine against HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Haemophilus influenzae type b polysaccharide-protein conjugate vaccine.

An Haemophilus influenzae type b capsular polysaccharide-protein conjugate has been prepared. The polysaccharide was coupled to the serotype II protein of group B meningococcus through the spacer 6-aminocaproic acid using cyanogen bromide and water soluble carbodiimide. The conjugate can be shown to be reproducible and is stable and highly immunogenic in mice and African green monkeys. Clinical evaluation of this conjugate in children 3 months to 4 years of age showed that it elicited an antibody titer to the polysaccharide moiety greater than 1000 ng/ml in children 8 months of age or older.

Animals↗
PubMed1986

The science of vaccines in present and future perspective.

Vaccinology, while affording great opportunities in the prevention of infectious diseases, also poses the problem of stretching the possible beyond the practicable. Politics, economics, and technology all come together at the point of resource allocation. It is important to maintain a balance between expenditure for the development of vaccines and for the application of vaccines if maximal good is to be achieved in this new era of technical opportunity. A promising approach is to include in single "polytopic" vaccines the largest number of immunogenic epitopes for the greatest number of important diseases.

Antibodies, Monoclonal↗
PubMed1986

New findings in live, attenuated hepatitis A vaccine development.

Strain CR326F of hepatitis A virus, derived from a fecal specimen of Costa Rican patient 033-03, was passed 15 times in fetal rhesus monkey kidney (FRhK6) cell cultures plus eight times in human diploid lung (MRC5) cell cultures to yield variant F and 16 times in MRC5 cell cultures to yield variant F'. Both variants were purified by limit dilution passages. Virulence for marmosets was assessed at six different passage levels, including variants F and F'. There was a gradual loss of virulence with in vitro passage. Variant F retained slight virulence for marmosets; variant F' showed no evidence of virulence. Both variants induced hepatitis A antibody in most marmosets that received them, and the animals were immune to infection when challenged. Variants F and F' were also assessed in chimpanzees. As in marmosets, F retained slight virulence but F' did not. Experimental vaccines made from variants F and F' were then inoculated parenterally into adult human volunteers. A portion of recipients of variant F showed brief, low-order enzyme elevations; none was seen in recipients of F', although their occurrence could not be totally ruled out. As in the animal models, F' appeared more attenuated than F. Most persons developed hepatitis A antibody, indicating the feasibility of developing a live, attenuated hepatitis A vaccine for human beings.

Animals↗
PubMed1986

Vaccines made from recombinant yeast cells.

Production of polypeptide and protein antigens through recombinant DNA technology in prokaryotic and certain eukaryotic cells in culture is facilitating the development of new vaccines that are safe, efficacious, and economically feasible to manufacture. A current example is that of human hepatitis B vaccine that, to the present, has been produced commercially using hepatitis B viral surface antigen (HBsAg) purified from the plasma of human carriers chronically infected with the virus. Production of plasma-derived vaccine is limited by the available supply of suitable carrier plasma and by the need to apply highly technical procedures to purify the antigen as well as to ensure inactivation of all infectious agents that might be present in human plasma.

Animals↗
PubMed1986

Vaccinology in practical perspective.

The nearly two centuries of success and failure in vaccinology have been superceded by an era of new opportunity employing hybridoma, recombinant, directed genetic alteration, and synthetic chemical technologies. Vaccines against a large number of infectious disease agents are now possible and they may be made practically useful by incorporating many relevant epitopes in complex "polytopic" vaccines. Though the technologies are well laid, hurdles still remain and these involve the need for understanding immunity in molecular terms. Developed countries typically underutilize vaccines even though resources are adequate. In Third World countries, where the need is greatest, there is least use because of the lack of resources. In pursuing vaccinology for Third World application, a balance needs to be sought, in the practical sense, between the amount of funds allocated to research and development and the amount allocated to utilization, lest vaccines be wastefully created that can never be used. Inclusion of the greatest possible number of needed immunodeterminants in the fewest number of vaccines is critical to practical application in developed as well as in developing countries.

Developing Countries↗
PubMed1985

Newer directions in vaccine development and utilization.

The gradually evolving technology for vaccine development from Jenner to recombinant genetics has provided both solid accomplishment and possible bases for prophylactic control of essentially all the infectious diseases of humans. The present review gives a prospective view of future vaccines and the new biotechnology as illustrated mainly in the examples of vaccines for control of hepatitis and of herpesvirus infections. Although vaccines offer great benefit for human health, their use is restricted in developing countries by lack of funds and in developed countries such as the United States by failure of application, mainly in adults. Practical matters relating to vaccine use must be resolved if there is to be justification for vaccine development.

Adjuvants, Immunologic↗
PubMed1984

Live attenuated varicella virus vaccine. Efficacy trial in healthy children.

We conducted a double-blind, placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine among 956 children between the ages of 1 and 14 years, with a negative clinical history of varicella. Of the 914 children who were serologically confirmed to be susceptible to varicella, 468 received vaccine and 446 received placebo. The vaccine produced few clinical reactions and was well tolerated. There was no clinical evidence of viral spread from vaccinated children to sibling controls. Approximately eight weeks after vaccination, 94 per cent of the initially seronegative children who received vaccine had detectable antibody to varicella. During the nine-month surveillance period, 39 clinically diagnosed cases of varicella, 38 of which were confirmed by laboratory tests, occurred among study participants. All 39 cases occurred in placebo recipients; no child who received vaccine contracted varicella. The vaccine was 100 per cent efficacious in preventing varicella in this population of healthy children (P less than 10(-9).

Adolescent↗