&nbsp;Researchers from the <a href="https://www.uchicagomedicine.org/" target="_blank" rel="noopener noreferrer">University of Chicago</a>, <a href="https://www.scripps.edu/" target="_blank" rel="noopener noreferrer">Scripps Research Institute</a>, and <a href="https://icahn.mssm.edu/" target="_blank" rel="noopener noreferrer">Icahn School of Medicine at Mount Sinai</a> report a new class of broadly neutralizing antibodies targeted against regions near the base of the influenza surface glycoprotein hemagglutinin (HA), which the authors named anchor antibodies in <a href="https://www.nature.com/articles/s41586-021-04356-8" target="_blank" rel="noopener noreferrer">Nature</a> Scientific Journal. The HA proteins on the surface of influenza virions are broken into two major domains, the HA-head and the HA-stalk. Antibodies that target the HA-head domain are critical components of immune protection against influenza infections, but the lack of conservation within these domains limits their protective capabilities to a narrow selection of influenza viruses. However, vaccines that target highly conserved portions of HA may provide immunity against a more diverse array of influenza viruses. The previously uncharacterized antibody class the authors identify provides a novel target for universal influenza vaccine design.&nbsp;<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/ab_6a78dc002f.jpg"></figure>&nbsp;<a href="https://www.cdc.gov/flu/about/burden/index.html" target="_blank" rel="noopener noreferrer">The Centers for Disease Control and Prevention (CDC)</a> estimate that between 9 million and 41 million influenza infections occur annually resulting in 12,000 to 52,000 deaths. Influenza vaccinations are a powerful disease prevention tool, but the high mutation rates and numerous influenza subtypes pose significant challenges. A universal vaccine that targets highly conserved regions of the virus, is effective against a wide range of influenza subtypes, and induces effective immunological memory would lessen the need to administer and update influenza vaccines annually.&nbsp;The authors generated 358 antibodies from the blood of individuals who were either infected with seasonal influenza, vaccinated against seasonal influenza, or part of a phase 1 universal vaccine clinical trial. The researchers found that nearly half of the antibodies tested targeted the conserved HA-stalk, and the majority (~80%) of those antibodies were directed to uncharacterized regions of the HA-stalk. The antibodies that are directed toward the uncharacterized stalk regions are referred to as “anchor-binding” antibodies, and were found to bind both a broad assortment of human H1N1 viruses and an H1N2 swine influenza virus. Additionally, a subset of the antibodies demonstrated neutralization activity toward an H2N2 virus, which suggests anchor-binding antibodies can also target non-H1 influenza viruses. Importantly, the antibodies were represented across many of the volunteers’ samples, which suggests they are common components of the immune antibody repertoire. Furthermore, anchor-binding antibodies were shown to have the ability to neutralize viruses carrying known immune evasion mutations, limiting the ability of viruses to develop into escape variants. The findings from the <a href="https://www.nature.com/articles/s41586-021-04356-8#citeas" target="_blank" rel="noopener noreferrer">Guthmiller et al. (2022)</a> study provides exciting insight on a previously undescribed class of antibodies and offers the next steps to developing universal influenza vaccines.<a href="https://www.nature.com/articles/s41586-021-04356-8" target="_blank" rel="noopener noreferrer">Guthmiller, J.J. et al. Broadly neutralizing antibodies target a hemagglutinin anchor epitope. Nature. https://doi.org/10.1038/s41586-021-04356-8. (2022).</a>

Publication Commentary

Influenza

CRIPT investigators labeled these antibodies, which target the base of the hemagglutinin (HA) protein of influenza, as ‘anchor antibodies’.&nbsp;

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CEIRR Researchers Reveal Novel Antibody Class Important for Future Universal Flu Vaccine Development

Researchers, including <a href="https://www.stjude.org/directory/s/stacey-schultz-cherry.html">Dr. Stacey Schultz-Cherry</a>, <a href="https://www.stjude.org/directory/t/paul-thomas.html">Dr. Paul Thomas</a>, and <a href="https://www.stjude.org/research/labs/mcgargill-lab.html">Dr. Maureen McGargill</a>, from the St. Jude Children’s Research Hospital Centers of Excellence for Influenza Research and Response (<a href="https://www.ceirr-network.org/centers/sjceirr">SJCEIRR</a>) addressed the important question of whether prior infection with coronaviruses, like the ones that cause common colds in humans, affects the level of disease caused by SARS-CoV-2. It is now well-established that SARS-CoV-2 infection causes diverse disease outcomes ranging from no symptoms to severe respiratory complications that can result in hospitalization and/or death. Although certain health conditions are known to increase risk of severe disease, the complete array of COVID-19 associated risk factors remains unknown.&nbsp;&nbsp;As of December 2022, more than 99 million <a href="https://covid.cdc.gov/covid-data-tracker/#datatracker-home">COVID-19 cases</a> and over one<img class="image-style-align-right" src="https://ceirr-public-website-static-prod.s3.amazonaws.com/CEIRR_Commentary_Lin_et_al_2021_image_31cdf109aa.jpg"> million deaths have been reported in the United States. To better understand the disease dynamics and susceptibility of the general population to SARS-CoV-2, it is vital to understand what variables contribute to disease severity. Currently, there are four common cold (non-SARS-CoV-2) coronaviruses in wide circulation across the globe that cause mild respiratory symptoms in humans. Dr. McGargill led a research team that investigated whether pre-existing immunity to common cold coronaviruses positively or negatively impacts SARS-CoV-2 immunity or COVID-19 clinical outcomes.&nbsp;Researchers collected a baseline blood sample from a cohort of St. Jude employees, who then underwent weekly nasal swabs to screen for SARS-CoV-2. Those who became infected with SARS-CoV-2 during the study provided post-infection blood samples, while those who did not test positive provided post-vaccination blood samples. Samples were assessed for antibodies against SARS-CoV-2 and the four common cold coronaviruses. The researchers found that nearly all participants had antibodies specific for the common cold coronaviruses. Interestingly, SARS-CoV-2 infection was associated with increased antibodies to the common cold viruses but did not provide protection against SARS-CoV-2. Rather, cross-reactive antibody levels correlated with higher SARS-CoV-2 specific antibodies, an indicator of more severe disease. The authors also speculate that pre-existing common cold antibodies may even delay production of SARS-CoV-2 specific antibodies. These findings suggest pre-existing common cold coronavirus antibodies that cross-react with SARS-CoV-2 may negatively impact COVID-19 clinical outcomes. The study provides important insight into the complex and difficult to characterize immune response to a novel virus when pre-existing immunity to a similar but distinct endemic virus is present.&nbsp;&nbsp;<a href="https://doi.org/10.1016/j.chom.2021.12.005">Lin, CY et al. (2022) Pre-existing humoral immunity to human common cold coronaviruses negatively impacts the protective SARS-CoV-2 antibody response. Cell Host and Microbe. 30(1): 83-96.e4</a>&nbsp;

SARS-CoV-2

Prior infection with common cold coronaviruses may delay SARS-CoV-2 specific antibody production, leading to worse COVID-19 clinical outcomes.

On left, blue SARS-CoV-2 virus with orange spike proteins protruding from surface. Behind & to right, scanning electron micrograph of cells-stained green that are infected by Omicron strain (blue). Image not to scale & all falsely colored

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CEIRR Researchers Find Immunity from Prior Common Cold Coronavirus Infections Inhibits the SARS-CoV-2 Antibody Response

<img class="image-style-align-left" src="https://ceirr-public-website-static-prod.s3.amazonaws.com/Peabody_Hotel1_small3_103436fd37.png">The 1st CEIRR Annual Network Meeting took place from August 14th-17th in Memphis, TN. Over 300 members of the CEIRR Network traveled to attend the in-person meeting, which was hosted at the Historic Peabody Hotel. A wealth of influenza and SARS-CoV-2 research was shared with over 45 speakers and 160 poster presentations taking place over the duration of the conference. The first day consisted of 9 breakout meetings that spanned various topics that included cohort sustainability, human subject research overviews, future effort strategies, and data management. The first day ended with dedicated breakout sessions for each CEIRR Center.The last three days of the meeting were dedicated to sharing cutting edge research across influenza and SARS-CoV-2 and consisted of 6 session topics, which included Immunology, Molecular Virology and Pathogenesis, Transmission and Adaption, Human-Animal Interface, Animal Surveillance, Human Cohorts and Surveillance, and Immunology and Vaccines. Two poster sessions spanning all the session topics were also held and highlighted the strong trainee presence at the meeting.&nbsp;Throughout the week the social events were an incredible success and helped trainees network with senior investigators. One highlight included a game where principal investigators (PIs) were given trading cards with their likeness and trainees were tasked with starting a conversation with PIs to collect as many trading cards as possible. The trainee who engaged in the most conversations and collected the most cards was given the immense honor of serving as the <a href="https://www.peabodymemphis.com/peabody-ducks/">Peabody Duckmaster</a>. This year's Duck Master was awarded to Dillon McBride, a graduate student in Dr. Andrew Bowman’s lab! The game provided a fun platform to facilitate new connections between researchers at different career stages.&nbsp;It is safe to say that the inaugural CEIRR Annual Network Meeting fostered many new collaborations and spurred creative new directions for the network. We look forward to another successful meeting in 2023!

Meetings

Conferences

The first CEIRR Annual Network Meeting was a hit, featuring 45 speakers, 160 posters, and tons of socializing.

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CEIRR Annual Network Meeting 2022

<img>&nbsp;<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/ASV_ASV_Info_Card_2022_small3_0bc6b9be79.png"></figure><img>In mid-July, the CEIRR Influenza Data Processing and Communication Center (<a href="https://www.ceirr-network.org/centers/idpcc">iDPCC</a>) attended the <a href="https://asv.org/asv2022/" target="_blank" rel="noopener noreferrer">American Society of Virology (ASV) Annual Meeting</a> in Madison, Wisconsin. The CEIRR booth was visited by attendees from both the CEIRR Network and external researchers. Word spread quickly throughout the conference of the amazing CEIRR gear available, with many of our Network researchers displaying their CEIRR “Ask me about my research” pins. Although the CEIRR branding was not the only thing catching the eye of attendees; the CEIRR Reagents and Pilot Research Program flyers had many interested in the resources that CEIRR supports.&nbsp;<h4 style="margin-left:360px;text-align:justify;">The CEIRR Network presented over 20 posters and 15 talks!</h4>The CEIRR booth was not alone in representing the Network. There were attendees from every Center, including:&nbsp;<ul><li style="text-align:justify;"><a href="https://vet.uga.edu/person/s-mark_tompkins/">Dr. Mark Tompkins</a> from <a href="https://www.ceirr-network.org/centers/cider">CIDER</a></li><li style="text-align:justify;"><a href="https://www.stjude.org/directory/s/stacey-schultz-cherry.html">Dr. Stacey Schultz-Cherry</a> from <a href="https://www.ceirr-network.org/centers/sjceirr">SJCEIRR</a></li><li style="text-align:justify;"><a href="https://publichealth.jhu.edu/faculty/1972/andrew-stanley-pekosz">Dr. Andrew Pekosz</a> from <a href="https://www.ceirr-network.org/centers/jh-ceirr">JH-CEIRR</a></li><li style="text-align:justify;"><a href="https://vbs.psu.edu/directory/tcs38">Dr. Troy Sutton</a> from <a href="https://www.ceirr-network.org/centers/emory-ceirr">Emory-CEIRR</a></li><li style="text-align:justify;"><a href="https://med.emory.edu/directory/profile/?u=SLAKDAW">Dr. Seema Lakdawala</a> from <a href="https://www.ceirr-network.org/centers/penn-ceirr">Penn-CEIRR</a></li><li style="text-align:justify;"><a href="https://profiles.mountsinai.org/florian-krammer">Dr. Florian Krammer</a> and <a href="https://www.uaa.alaska.edu/academics/college-of-arts-and-sciences/departments/biological-sciences/faculty/bortz.cshtml">Dr. Eric Bortz</a> from <a href="https://www.ceirr-network.org/centers/cript">CRIPT</a></li><li style="text-align:justify;">And many more!</li></ul>Check out the <a href="https://twitter.com/search?q=(from%3ACEIRRNetwork)%20until%3A2022-07-19%20since%3A2022-07-13&amp;src=typed_query" target="_blank" rel="noopener noreferrer">CEIRR Twitter coverage</a> for the sightings we caught.

The CEIRR Network attended the American Society of Virology (ASV) 2022 meeting in Madison, Wisconsin.

3 CEIRR-brand blue & green virion graphics as stickers & pins. Other pins read: Ask me about my Influenza, MERS-CoV & SARS-CoV-2 research!

CEIRR

The Microbial Pathogenesis Conference: Mechanisms of Infectious Disease

When

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