{"id":1071,"date":"2023-11-19T18:46:07","date_gmt":"2023-11-19T23:46:07","guid":{"rendered":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/?p=1071"},"modified":"2023-11-19T18:46:07","modified_gmt":"2023-11-19T23:46:07","slug":"mrna-unpacking-the-research-that-led-to-the-covid-19-vaccines-and-the-2023-nobel-prize-in-medicine","status":"publish","type":"post","link":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/science\/mrna-unpacking-the-research-that-led-to-the-covid-19-vaccines-and-the-2023-nobel-prize-in-medicine\/","title":{"rendered":"mRNA: Unpacking the Research that led to the COVID-19 Vaccines and the 2023 Nobel Prize in Medicine"},"content":{"rendered":"

\u00a0 \u00a0 \u00a0 \u00a0 By 2023, 81.4% of the United States population have received at least one dose of the COVID-19 mRNA vaccine, and just about everyone has heard of these lifesaving shots (CDC, 2023). But how many of us actually know how they work? In general, vaccinations expose the body to a weakened strain of a virus that initiates an immune response so that the virus can be recognized, and quickly neutralized, in the future (Jain, 2021). This works because of the structure of our immune system, which is split up into innate immunity and adaptive immunity. Innate immunity is the immediate response that our bodies put up when exposed to a pathogen; it sends out macrophages to gobble up infected cells, creates an inflammatory response to kill off the infection, and uses a host of molecules and pathways to destroy the virus. Adaptive immunity involves the presence of B and T cells, which arise in a viral infection and create immunological memory through antibodies and memory cells so that a future infection of the same virus is immediately recognized and shut down. Vaccines work to stimulate this adaptive immunity, while minimizing innate immunity.<\/span><\/p>\n

\u00a0 \u00a0 \u00a0 \u00a0 mRNA vaccines use this same basic principle, but instead of injecting a weakened strain of the actual virus into someone, they instead inject a piece of mRNA, or messenger RNA, which codes for a viral protein that stimulates this immune response (Jain, 2021).<\/span><\/p>\n

\"\"<\/p>\n

Figure 1: The methodology of mRNA vaccines. Adapted from Jain, et. al., 2021<\/span><\/p>\n

mRNA vaccines are much easier to make than traditional vaccines because they don\u2019t require growing and inactivating a virus, and they don\u2019t carry the risk that live vaccines have of infecting the subject, but up until recently, they weren\u2019t even remotely possible because <\/span>in vitro<\/span><\/i> mRNA would create a huge inflammatory response when entering the body (Karik\u00f3, 2005). However, Hungarian biochemist Katalin Karik\u00f3 and her colleague Drew Weissman were undeterred, and their research to create mRNA without an inflammatory response paved the way for mRNA vaccines and won them the Nobel Prize in Medicine in 2023 (Karik\u00f3, 2005).<\/span><\/p>\n

\u00a0 \u00a0 \u00a0 \u00a0 Karik\u00f3 and Weissman\u2019s research focused on <\/span>in vitro<\/span><\/i> mRNA\u2019s stimulation of Toll-like receptors (TLRs), which recognize pathogens and activate signaling pathways leading to an inflammatory response (Karik\u00f3, 2005). They discovered that mammalian mRNA, which doesn\u2019t stimulate an immune response, contains many base pair modifications, whereas bacterial RNA, which is known to stimulate a response, has no modifications (Karik\u00f3, 2005). <\/span>In vitro<\/span><\/i> mRNA, grown in a lab rather than from mammalian cell cultures, also has no, or very few, modifications. This led the researchers to question whether base pair modifications were how cells distinguished between foreign and non-foreign RNA, and thus which pieces of RNA stimulate an immune response (Karik\u00f3, 2005). They discovered that <\/span>in vitro<\/span><\/i> RNA activates three main TLRs known for activating an inflammatory response, but that nucleoside modifications limit that activation. Most importantly, they discovered that the suppressed immune response is proportional to the number of nucleotide modifications, and that these modifications also increase the stability of <\/span>in vitro<\/span><\/i> mRNA in the body, another original roadblock in the usage of mRNA for vaccines. (Karik\u00f3, 2005).<\/span><\/p>\n

\"\"<\/p>\n

Figure 2: The use of base modifications to suppress inflammatory response of RNA. Adapted from Nobelprize.org<\/span><\/p>\n

\u00a0 \u00a0 \u00a0 \u00a0 <\/span>Combined with later research also by Karik\u00f3 and Weissman discovering that modified base-pairs also create increased protein production and other research designing more stable lipid carriers to deposit the mRNA into human cells, mRNA became a promising new vaccine technology, eventually allowing the COVID-19 vaccines to be produced in record times, shortening the pandemic and granting all of us our lives back. But the road to Karik\u00f3\u2019s research being recognized, and especially the road to the Nobel Prize, was not predetermined. Karik\u00f3\u2019s research was long overlooked, in part because of her identity as a Hungarian immigrant. She was \u201cdemoted four times\u201d at UPenn, being told that her research didn\u2019t measure up to their standards, but she continued to persevere, making her both a scientific success story, and a personal one (Shrikant, 2023). The COVID-19 vaccines created by Pfizer and Moderna were the first mRNA vaccines to be released, but future research is focusing on creating a universal flu vaccine and possibly even an HIV vaccine, all using mRNA technologies, which could drastically improve the landscape of viral infections, both in the US and across the globe.<\/span>\u00a0\u00a0<\/span><\/p>\n

 <\/p>\n

Literature Cited<\/b><\/p>\n

Karik\u00f3, K., Buckstein, M., Ni, H., & Weissman, D. (2005). Suppression of RNA Recognition by Toll-Like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. <\/span>Immunity<\/span><\/i>, <\/span>23<\/span><\/i>(2), 165\u2013175.<\/span> https:\/\/doi.org\/10.1016\/j.immuni.2005.06.008<\/span><\/a><\/p>\n

\u00a0<\/span>Karik\u00f3, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S., & Weissman, D. (2008). Incorporation of Pseudouridine into mRNA yields Superior Nonimmunogenic Vector with Increased Translational Capacity and Biological Stability. <\/span>Molecular Therapy<\/span><\/i>, <\/span>16<\/span><\/i>(11), 1833\u20131840.<\/span> https:\/\/doi.org\/10.1038\/mt.2008.200<\/span><\/a><\/p>\n

\u00a0<\/span>Jain, S., Venkataraman, A., Wechsler, M. E., & Peppas, N. A. (2021). Messenger RNA-Based Vaccines: Past, Present, and Future Directions in the Context of the COVID-19 Pandemic. <\/span>Advanced Drug Delivery Reviews<\/span><\/i>, <\/span>179<\/span><\/i>, 114000.<\/span> https:\/\/doi.org\/10.1016\/j.addr.2021.114000<\/span><\/a><\/p>\n

\u00a0<\/span>The Nobel Prize in Physiology or Medicine 2023<\/span><\/i>. (n.d.). NobelPrize.Org. Retrieved October 22, 2023, from<\/span> https:\/\/www.nobelprize.org\/prizes\/medicine\/2023\/press-release\/<\/span><\/a><\/p>\n

\u00a0<\/span>CDC. (2020, March 28). <\/span>Covid Data Tracker<\/span><\/i>. Centers for Disease Control and Prevention.<\/span> https:\/\/covid.cdc.gov\/covid-data-tracker<\/span><\/a><\/p>\n

Shrikant, A. (2023, October 6). <\/span>Nobel Prize Winner Katalin Karik\u00f3 was \u201cdemoted 4 times\u201d at her old job. How she persisted: \u201cYou have to focus on what\u2019s next.\u201d<\/span><\/i> CNBC. <\/span>https:\/\/www.cnbc.com\/2023\/10\/06\/nobel-prize-winner-katalin-karik-on-being-demoted-perseverance-.html<\/span><\/a>\u00a0<\/span><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

\u00a0 \u00a0 \u00a0 \u00a0 By 2023, 81.4% of the United States population have received at least one dose of the COVID-19 mRNA vaccine, and just about everyone has heard of these lifesaving shots (CDC, 2023). But how many of us actually know how they work? In general, vaccinations expose the body to a weakened strain […]<\/p>\n","protected":false},"author":680,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_genesis_hide_title":false,"_genesis_hide_breadcrumbs":false,"_genesis_hide_singular_image":false,"_genesis_hide_footer_widgets":false,"_genesis_custom_body_class":"","_genesis_custom_post_class":"","_genesis_layout":"","footnotes":""},"categories":[63,64,1],"tags":[],"class_list":{"0":"post-1071","1":"post","2":"type-post","3":"status-publish","4":"format-standard","6":"category-biology","7":"category-chem-biochem","8":"category-science","9":"entry","10":"has-post-thumbnail"},"featured_image_src":null,"featured_image_src_square":null,"author_info":{"display_name":"Maren Cooper '27","author_link":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/author\/mcooper5\/"},"_links":{"self":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts\/1071","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/users\/680"}],"replies":[{"embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/comments?post=1071"}],"version-history":[{"count":0,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/posts\/1071\/revisions"}],"wp:attachment":[{"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/media?parent=1071"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/categories?post=1071"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/students.bowdoin.edu\/bowdoin-science-journal\/wp-json\/wp\/v2\/tags?post=1071"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}