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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↗
PubMed1979

High-resolution flow-zonal centrifuge system.

A modified CF-32 Beckman flow centrifuge rotor has been developed that provides a long sedimentation path length with high gravitational force at the gradient sample interface. The modified rotor exhibits excellent separative capability and extraction efficiency when applied to purification of human influenza B and herpes simplex viruses.

Centrifugation, Zonal↗
PubMed1979

Enzyme-linked immunosorbent assay for measurement of antibodies against pneumococcal polysaccharide antigens: comparison with radioimmunoassay.

An enzyme-linked immunosorbent assay (ELISA) for measuring antibodies against each of 14 polysaccharides in contemporary pneumococcal vaccine is described, and the findings of tests of paired sera from vaccinated human subjects are compared with those obtained by radioimmunoassay. The findings were in very poor agreement, and this appears to be due to the lesser ability of the ELISA procedure to measure antibody of low avidity. The ELISA procedure described here is not considered to be a satisfactory substitute for radioimmunoassay for measuring antibody responses to pneumococcal vaccine.

Antibodies, Bacterial↗