McLellan and his team designed a special form of the spike protein that makes it more likely to be effective as a vaccine antigen, a part of the virus that can be used to stimulate antibody production in advance, and thus help the body fight off infection.<\/p>\n \u201cIt is exciting to see the huge impact of this novel research by Jason and his colleagues,\u201d says Duane Compton, PhD, dean of the Geisel School of Medicine. \u201cIt is a good reminder of the importance of basic science research and its ability to save lives around the world.\u201d<\/p>\n Four years ago, McLellan and his team made their first major breakthrough at Dartmouth working with a human coronavirus known as HKU1, one of the causes of the common cold and closely related to more potent and deadly coronaviruses such as SARS (Severe Acute Respiratory Syndrome)-CoV and MERS (Middle East Respiratory Syndrome)-CoV.<\/p>\n \u201cOur goal was to determine the first three-dimensional structure of a coronavirus spike protein,\u201d recalls McLellan, now an associate professor of molecular biosciences at the University of Texas at Austin. \u201cWe wanted this information so we could do more structure-based vaccine design. This involved using these structures to do protein engineering and identify substitutions or mutations we could make in the proteins that would cause the spikes to be more stable.\u201d<\/p>\n Stability is important, he says, because it makes the antigen a better target for antibodies, molecules the body makes to fight infection. Vaccines work by training the immune system to make antibodies that can recognize and bind to the antigen, blocking its entry into host cells.<\/p>\n Mapping the structure of the HKU1 spike protein enabled the researchers to then design their antigen, while they were working on creating a coronavirus vaccine antigen for MERS. The stabilized antigen proved effective, not only for MERS but also many of the most dangerous and deadly coronaviruses, including now SARS-CoV-2 (the virus that causes COVID-19).<\/p>\n \u201cIt\u2019s hard to attribute the high efficacy rates seen so far in the vaccine just to the stabilizing mutations we added\u2014the companies have also developed some excellent platforms\u2014but we think the stabilizing mutations have helped,\u201d says McLellan. \u201cAnd I think the success of the prior research has allowed Pfizer\/BioNTech to have the confidence to rapidly choose their antigen and move quickly into manufacturing large quantities for clinical trials.\u201d<\/p>\n \u201cIt is very gratifying to see fundamental discoveries from the McLellan research team translated into a leading COVID-19 vaccine,\u201d says Charles Barlowe, PhD, chair of biochemistry and cell biology at Geisel. \u201cJason\u2019s contributions to vaccine development are also a wonderful testament to his insightful and collaborative approach to science.\u201d<\/p>\n![\"\"](\"https:\/\/geiselmed.dartmouth.edu\/news\/wp-content\/uploads\/sites\/2\/2020\/12\/McLellan_web-295x360.jpg\")
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