A "Pure" Organic Chemists Downward Path: Chapter 2-The Years at P. and S.

Heidelberger, Michael

doi:10.1146/annurev.bi.48.070179.000245

Cited by 17 publications

(6 citation statements)

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“…From 1942 to 1945, Heidelberger and Colin M. MacLeod (1909–1972) took advantage of the preceding developments in polysaccharide technology to develop and test a pneumococcal polysaccharide vaccine at the US Army Air Force Technical School, Sioux Falls, South Dakota [53,56,57]. In this institutional setting with a high incidence rate of pneumococcal infections, they tested capsular polysaccharides against pneumococcal serotypes 1, 2, 5 and 7.…”

Section: Wartime Urgencies Revisitedmentioning

confidence: 99%

A century of pneumococcal vaccination research in humans

Grabenstein

Klugman

2012

Clinical Microbiology and Infection

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Sir Almroth Wright coordinated the first trial of a whole-cell pneumococcal vaccine in South Africa from 1911 to 1912. Wright started a chain of events that delivered pneumococcal vaccines of increasing clinical and public-health value, as medicine advanced from a vague understanding of the germ theory of disease to today's rational vaccine design. Early whole-cell pneumococcal vaccines mimicked early typhoid vaccines, as early pneumococcal antisera mimicked the first diphtheria antitoxins. Pneumococcal typing systems developed by Franz Neufeld and others led to serotype-specific whole-cell vaccines. Pivotally, Alphonse Dochez and Oswald Avery isolated pneumococcal capsular polysaccharides in 1916-17. Serial refinements permitted Colin MacLeod and Michael Heidelberger to conduct a 1944-45 clinical trial of quadrivalent pneumococcal polysaccharide vaccine (PPV), demonstrating a high degree of efficacy in soldiers against pneumococcal pneumonia. Two hexavalent PPVs were licensed in 1947, but were little used as clinicians preferred therapy with new antibiotics, rather than pneumococcal disease prevention. Robert Austrian's recognition of high pneumococcal case-fatality rates, even with antibiotic therapy, led to additional trials in South Africa, the USA and Papua New Guinea, with 14-valent and 23-valent PPVs licensed in 1977 and 1983 for adults and older children. Conjugation of polysaccharides to proteins led to several pneumococcal conjugate vaccines licensed since 2000, enabling immunization of infants and young children and resultant herd protection for all ages. Today, emergence of disease caused by pneumococcal serotypes not included in various vaccine formulations fuels research into conserved proteins or other means to maximize protection against more than 90 known pneumococcal serotypes.

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Section: Wartime Urgencies Revisitedmentioning

confidence: 99%

A century of pneumococcal vaccination research in humans

Grabenstein

Klugman

2012

Clinical Microbiology and Infection

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“…“This was all very well for antibodies to polysaccharides,” noted Heidelberger in a 1979 article, “but what about those elicited by the vast numbers of protein antigens?” ( 3 ). As 15 N had not yet been discovered, Heidelberger and Kendall instead used a colorful trick to distinguish antigen-derived nitrogen from antibody-derived nitrogen.…”

Section: An Eye For Colormentioning

confidence: 99%

Michael Heidelberger and the demystification of antibodies

Epps

2006

The Journal of Experimental Medicine

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“…The more they purified the reactive substance the less nitrogen it contained. When it was virtually nitrogen-free, recalled Heidelberger in a 1979 article, Avery ventured a guess: “Could it be a carbohydrate?” ( 2 ). Chemical analysis confirmed its sugary character, and subsequent studies of other pneumococcal serotypes revealed that each bacterial capsule had a distinct polysaccharide signature.…”

Section: All About Nitrogenmentioning

confidence: 99%

“…Heidelberger and Avery's discovery came at a time when antibodies were regarded—by those who believed they existed at all—as mysterious substances that floated around in serum. “It appeared to me that there was a crying need to determine the true nature of antibodies,” wrote Heidelberger in 1979, “and that until this was done there could be no end to the polemics and uncertainties that were plaguing immunology” ( 2 ). Heidelberger later purified the antibodies from his precipitin reactions and showed that they themselves were proteins.…”

Section: Antibodies Solidifiedmentioning

confidence: 99%