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NOVARTIS
IMPROVING POTENCY OF SUGAR VACCINES IMMUNOLOGY: Efficacy of glycoconjugate vaccines depends on locations of sugar-protein links
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LYCOCONJUGATE VACCINES can spur the
body’s immune system to seek out and attack pathogens or cancer cells on the basis of which specific sugar chains decorate those targets. Approved vaccines for conditions such as meningitis and pneumonia work through such sugar-based antigens. To make glycoconjugate vaccines, scientists nearly always attach the sugars randomly to amino acids in carrier proteins to enhance the carbohydrates’ ability to elicit an immune response. Now, researchers have used several reactions to link sugars to specific amino acids in a carrier protein and have found that where they attached the carbohydrates affected the level of responses to the vaccine (Angew. Chem. Int. Ed. 2015, DOI: 10.1002/ anie.201506112). The work shows that better control over attachment points used in the conjugation process could aid the development of better characterized vaccines with improved efficacy and more consistent molecular properties. The investigators—Qi-Ying Hu of Novartis Institutes for BioMedical Research, in Cambridge, Mass.; Francesca Micoli of Sclavo Behring Vaccines Institute for Global Health, in Siena, Italy; and coworkers— note that this is the first comparative study of the immune effects of different sugar conjugation sites. The sugar, or glycan, in the study is a lipopolysaccharide antigen from Salmonella enterica serovar
Typhimurium, which causes a form of food poisoning that can be fatal, especially in immunocompromised patients. There are no current vaccines for this pathogen. The research team used several site-selective conjugation methods, including two they developed, to attach the antigen via a linker to specific cysteines, lysines, tyrosines, glutamates, and aspartates in a carrier protein called CRM197. When they injected the vaccines into mice, the amount of antibacterial antibodies generated varied significantly depending on the conjugation site—as much as an order of magnitude. Attaching a single sugar to both cysteines of a disulfide bond produced one of the more productive glycoconjugates. The conjugate was as active as ones with multiple sugars. This demonstrates how picking a specific sugar-linkage site can help optimize glycoconjugate potency, Micoli says, because a conjugate with multiple sugars is often more effective than a conjugate with just one. Gonçalo Bernardes, an expert on site-selective protein modification at the University of Cambridge and the University of Lisbon, comments that this is the first structure-activity relationship study that clearly shows that attachment site can play a key role in immune responses to glycoconjugates. Conjugation site should be taken into consideration in the design of future carbohydrate-based vaccines, he says. However, Bernardes notes that scientists will also need to assess the effects on vaccine efficacy of the lengths of chemical linkers used to attach carbohydrate antigens to amino acids.—STU
This model of a glycoconjugate shows a linker connecting a glycan antigen (purple and orange) to cysteines from a disulfide bond (yellow) on the carrier protein CRM197 (gray). The synthetic method is specific, attaching the sugar at one of the protein’s disulfides but not the other (lower left).
BORMAN
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Yb
PERIODIC TABLE Ytterbium loses weight Ytterbium is a bit lighter than previously thought: Its standard atomic weight is now 173.045, down from 173.054, as approved by the International Union of Pure & Applied Chemistry (IUPAC) in August. The IUPAC Commission on Isotopic Abundances & Atomic Weights evaluates atomic weights every two years. Which elements it tackles depends on what new data are available. This year, only ytterbium made the docket, based on mass spectrometric analysis carried out by China’s National Institute of Metrology
(J. Anal. At. Spectrom. 2015, atomic weight is calculated ytterbium DOI: 10.1039/c5ja00054h). as a weighted average of 173.045 On average, the atomic seven isotopes, based on weights of individual elements quantifying their natural get updated about every 14 years, says the abundances on Earth. IUPAC revised the commission’s chair, Juris Meija of the Naweight to 173.04 in 1934 based on chemitional Research Council of Canada. Some cal analysis that was later confirmed last longer than others—lead’s was last by mass spectrometry. The union then set in 1969, for example—not necessarily adjusted the value to 173.054 in 2007 because the numbers are solid but beon the basis of additional mass spectrocause the experiments require expensive, metric work that was combined with the isotopically enriched samples, Meija says. latest results for this year’s update, Meija In ytterbium’s case, its standard says.—JYLLIAN KEMSLEY
CEN.ACS.ORG
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SEPTEMBER 21, 2015
