Although many avian influenza viruses cause only mild disease, Highly Pathogenic Avian Influenza (HPAI) is often fatal in birds and is known to sporadically spillover to mammals. Avian influenza viruses can become highly pathogenic in birds when one of the surface proteins, known as hemagglutinin (HA), acquires a mutation that allows greater viral spread&nbsp;throughout the host.<a href="https://www.nature.com/articles/s41577-023-00868-8" target="_blank" rel="noopener noreferrer">1</a> Increased spread of these viruses increases the chances that they will acquire genomic variations that lead to highly pathogenic forms. Historically, the spread of HPAI H5 and H7 subtypes have resulted in great economic loss due to the severe disease and death they cause in domestic poultry. To date, however, HPAI have rarely infected mammals and have very limited capacity to be transmitted from human to human, with nearly all documented human cases resulting directly from close contact with infected birds. &nbsp;Confirmed HPAI H5N1 infections in humans since 2003 have resulted in a greater than 50% case fatality rate. Due to the high mortality rates and concerns over their potential to cause a pandemic, HPAI and their spread through wild bird and mammal populations are under close surveillance.<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/domestic_chickens_350x197_7e3bfbefc7.png"><figcaption>Domestic chickens. Image courtesy of CDC.</figcaption></figure>Since late 2020, HPAI H5N1 has devastated the U.S. poultry industry causing almost 60 million&nbsp;<a href="https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm" target="_blank" rel="noopener noreferrer">poultry deaths</a> and has led to renewed conversations about whether preventative commercial poultry vaccination programs should be undertaken.<a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">2</a> Further, HPAI has infected wild bird populations at an alarming rate. Current reports from the World Animal Health Information System (WAHIS) sit at around 68,000 wild bird casualties, though due to less surveillance in wild populations some experts estimate the true extent of wild bird mortality in the millions.<a href="https://www.biorxiv.org/content/10.1101/2023.05.02.539182v1.full.pdf+html" target="_blank" rel="noopener noreferrer">3</a>&nbsp;Recent reports&nbsp;of HPAI H5N1 spillover into mammals has increased concerns and scientific dialogue about the pandemic potential of HPAI and prevention strategies.<a href="https://now.tufts.edu/2023/03/15/bird-flu-associated-hundreds-seal-deaths-new-england-2022-tufts-researchers-find" target="_blank" rel="noopener noreferrer">4</a> Dr. Jonathan Runstadler, of Tufts University and member of the Center for Research on Influenza Pathogenesis and Transmission (<a href="https://www.ceirr-network.org/centers/cript" target="_blank" rel="noopener noreferrer">CRIPT</a>), found a large mortality event of over 300 harbor seals in New England attributed to HPAI. As reported by the <a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">New York Times (NYT)</a>,&nbsp;the recent avian influenza outbreak is the largest in U.S. history and has led to increased monitoring efforts by the Centers for Disease Control (<a href="https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm" target="_blank" rel="noopener noreferrer">CDC</a>) in cooperation with state and local public health departments. Additionally, the recent outbreak has led to increased poultry vaccine testing by the federal Agriculture Department. Dr. Anice Lowen, Principal Investigator of Emory University CEIRR (<a href="https://www.ceirr-network.org/centers/emory-ceirr" target="_blank" rel="noopener noreferrer">Emory-CEIRR</a>), mentioned to the NYT that vaccinating poultry could “reduce the potential for viral evolution,” which may limit new HPAI H5N1 variants and “exposures to humans.”<a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">2</a> Dr. Richard Webby, Principal Investigator of St. Jude CEIRR (<a href="https://www.ceirr-network.org/centers/sjceirr" target="_blank" rel="noopener noreferrer">SJCEIRR</a>), told the NYT that avian influenza “is here to stay” in the US, highlighting the need for mitigation efforts.<a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">2</a> The Washington Post recently reported that agriculture officials in the Biden Administration are testing four avian influenza vaccines in poultry to mitigate transmission at farms and minimize economic consequences such as rising egg prices.<a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">2</a>,<a href="https://www.washingtonpost.com/business/2023/05/02/bird-flu-vaccine-biden/" target="_blank" rel="noopener noreferrer">5</a><figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/american_wigeon_350x197_9227a6260e.png"><figcaption>American Wigeon. Image courtesy of CDC.</figcaption></figure>It is important to acknowledge that even with the current spread of HPAI H5N1 within commercial bird populations, transmission to humans has remained incredibly rare and there have been no recorded cases of human-to-human transmission from this outbreak. An <a href="https://www.nature.com/articles/s41577-023-00868-8" target="_blank" rel="noopener noreferrer">article recently published in Nature</a> by Dr. Florian Krammer, CRIPT, and Dr. Stacey Schultz-Cherry, co-Principal Investigator of SJCEIRR, provides an overview of the past HPAI outbreaks and frames the current and future risks posed by HPAI. The authors emphasize that, although the apparent spread of H5N1 viruses between mammals does increase concerns over the possibility that the same viruses could acquire the ability to transmit between humans, it is still “not a reason for panic”.<a href="https://www.nature.com/articles/s41577-023-00868-8" target="_blank" rel="noopener noreferrer">1</a> The authors point to antivirals that can target H5N1 influenza viruses, providing as a potential immediate treatment option, as well as seasonal exposure to the N1 neuraminidase (NA) component of the viruses, which likely provides partial immunity to the adult population. Nevertheless, Dr. Krammer and Dr. Schultz-Cherry suggest pandemic risk reduction actions should be undertaken including efforts to increase public awareness, informing physicians to be vigilant about monitoring influenza infections, starting production and stockpiling of H5N1 vaccines, and scrutinizing safe farm practices.&nbsp;To read more about the HPAI H5N1 outbreaks, check out:1&nbsp;<a href="https://www.nature.com/articles/s41577-023-00868-8" target="_blank" rel="noopener noreferrer">Krammer F and Schultz-Cherry S. (2023) We need to keep an eye on avian influenza. Nature Reviews Immunology. 23: 267-268.</a>2&nbsp;The New York Times: <a href="https://www.nytimes.com/2023/03/06/us/politics/bird-flu-vaccine-chickens.html?smid=url-share" target="_blank" rel="noopener noreferrer">U.S. Considers Vaccinating Chickens Amid Bird Flu Outbreak</a>3 <a href="https://www.biorxiv.org/content/10.1101/2023.05.02.539182v1.full.pdf+html" target="_blank" rel="noopener noreferrer">Klaassen M and Wille M. (2023) Wild birds' plight and role in the current bird flu panzootic. bioRxiv. https://doi.org/10.1101/2023.05.02.539182</a>4&nbsp;Tufts Now:&nbsp;<a href="https://now.tufts.edu/2023/03/15/bird-flu-associated-hundreds-seal-deaths-new-england-2022-tufts-researchers-find" target="_blank" rel="noopener noreferrer">Bird Flu Associated with Hundreds of Seal Deaths in New England in 2022, Tufts Researchers Find</a>5 The Washington Post: <a href="https://www.washingtonpost.com/business/2023/05/02/bird-flu-vaccine-biden/" target="_blank" rel="noopener noreferrer">Biden administration tests vaccines to fight avian flu that sent egg prices soaring</a>

In The News

Influenza

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CRIPT

Emory-CEIRR

SJCEIRR

CEIRR researchers respond to the avian influenza outbreaks with calls for action.

Duck (top) and chicken (bottom) with #FightFlu in a bubble at bottom right. Image courtesy of CDC.

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The Highly Pathogenic Avian Influenza Outbreak Devastates Poultry and Wild Bird Populations

<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/Walter_200x200_636fe39eca.png" alt="Walter Orenstein, MD"><figcaption>Walter Orenstein, MD, announces his retirement.</figcaption></figure>Dr.&nbsp;Walter Orenstein, MD, has decided to retire from Emory University effective September 1st, 2023. Walt has been with Emory since 1994 with appointments in both the School of Medicine and&nbsp;the Rollins School of&nbsp;Public Health. In addition to one primary and three joint professor appointments, Walt has been involved with the CEIRR/CEIRS program since 2007.&nbsp;Additionally, Walt&nbsp;is the current Director of the Emory Program for Vaccine Policy and Development and Associate Director of the Emory Vaccine Center.&nbsp;On April 1st,&nbsp;Dr. Anice Lowen, PhD will become Principal Investigator of&nbsp;<a href="https://www.ceirr-network.org/centers/emory-ceirr" target="_blank" rel="noopener noreferrer">Emory-CEIRR</a>, and Walt will transition to the Co-PI until his September retirement.

Recognition

Walt Orenstein will retire from Emory University on September 1st, 2023. Anice Lowen will become PI of Emory-CEIRR on April 1st, and Walt will become Co-PI.

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Announcing Dr. Walter Orenstein's Retirement

Dr. Florian Krammer, Center for Research on Influenza Pathogenesis and Transmission (<a href="https://www.ceirr-network.org/centers/cript" target="_blank" rel="noopener noreferrer">CRIPT</a>), and Dr. Alessandro Sette, St. Jude Center of Excellence for Influenza Research and Response (<a href="https://www.ceirr-network.org/centers/sjceirr" target="_blank" rel="noopener noreferrer">SJCEIRR</a>), were recently elected to the American Academy of Microbiology’s class of 2023.&nbsp;<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/Sette_Krammer_thumbnail_400x400_685a3f1fb0.png"><figcaption>Dr. Florian Krammer (left) and Dr. Alessandro Sette (right) elected to the American Academy of Microbiology Class of 2023.</figcaption></figure>Dr. Krammer is a Professor of Vaccinology in the Department of Microbiology and Department of Pathology, Molecular and Cell-based Medicines at the Icahn School of Medicine at Mount Sinai. His CEIRR research is focused on improving the understanding of broad immune responses that are directed toward RNA virus surface proteins to inform future vaccine and therapeutics development. Additionally, Dr. Krammer is the Principal Investigator of the Sinai-Emory Multi-Institutional Collaborative Influenza Vaccine Innovation Center (<a href="https://www.niaidcivics.org/sinai-emory-multi-institutional-civic/" target="_blank" rel="noopener noreferrer">SEM-CIVIC</a>), where his lab conducts research aimed at developing influenza vaccines that confer longer-lasting protection against a broad range of influenza viruses.Dr. Sette is a professor within the Center for Autoimmunity and Inflammation and Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology. His research defines and tests the structures recognized by the immune system, known as epitopes, to characterize what constitutes effective and ineffective immune responses to a variety of diseases. Dr. Sette’s work with CEIRR focuses on assessing T cell and memory B cell profiles against SARS-CoV-2 variants. His laboratory’s most recent work has centered around investigating the immune evasive properties of emergent and biodefense-related diseases, with the goal of informing the development of novel therapeutics. Dr. Sette has also played an integral role in the development of the national Immune Epitope Database (<a href="https://www.iedb.org/" target="_blank" rel="noopener noreferrer">IEDB</a>), a freely available comprehensive multi-species epitope catalog and bioinformatics tool suite.&nbsp;As one of the world’s largest scientific societies, the American Society for Microbiology (ASM) has elected more than 2,600 researchers over the past five decades to its leadership group, the American Academy of Microbiology (AAM). Nominations are conducted each year by current AAM members and nominees are reviewed by the Academy Subcommittee on Elections and Governors. The academy’s mission is to recognize individuals for their accomplishments in and service to the field of microbial sciences as well as their dedication to high ethical standards. Congratulations to both Dr. Krammer and Dr. Sette!For a full list of the 2023 American Academy of Microbiology fellows click&nbsp;<a href="https://asm.org/Press-Releases/2023/February/65-Fellows-Elected-into-the-American-Academy-of-Mi" target="_blank" rel="noopener noreferrer">here</a>.

Awards

Two CEIRR researchers, Florian Krammer and Alessandro Sette, among 65 fellows elected to the American Academy of Microbiology for 2023.

Headshots of Dr. Florian Krammer (left) and Dr. Alessandro Sette (right)

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Florian Krammer and Alessandro Sette elected to the American Academy of Microbiology Class of 2023

<figure class="image image-style-align-left"><img src="https://ceirr-public-website-static-prod.s3.amazonaws.com/Universal_Flu_Vaccine_400x225_a549ff265c.jpg" alt="Graphical depiction of 20 HA mRNA-lipid nanoparticle vaccine. Image credit: NIH Director's Blog."><figcaption>Graphical depiction of 20 HA mRNA-lipid nanoparticle vaccine. Image credit: NIH Director's Blog.</figcaption></figure>Influenza vaccines are given each year to protect against specific strains circulating in humans predicted to be the most prevalent during flu season. These vaccines are a critical public health tool to fight seasonal influenza but are unlikely to provide protection against viruses emerging from animals with pandemic potential. Researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID) <a href="https://www.ceirr-network.org/" target="_blank" rel="noopener noreferrer">Centers of Excellence for Influenza Research and Response (CEIRR)</a> and <a href="https://www.niaidcivics.org/" target="_blank" rel="noopener noreferrer">Collaborative Influenza Vaccine Innovation Centers (CIVICs)</a> developed an experimental multivalent influenza vaccine that extends immune responses beyond the narrow protection that seasonal vaccines provide.&nbsp;The study led by <a href="https://www.med.upenn.edu/apps/faculty/index.php/g20001880/p27057" target="_blank" rel="noopener noreferrer">Dr. Scott Hensley's</a> lab at the <a href="https://www.upenn.edu/" target="_blank" rel="noopener noreferrer">University of Pennsylvania</a>, and in collaboration with <a href="https://med.emory.edu/directory/profile/?u=SLAKDAW" target="_blank" rel="noopener noreferrer">Dr. Seema Lakdawala’s</a> lab, both part of <a href="https://www.ceirr-network.org/centers/penn-ceirr" target="_blank" rel="noopener noreferrer">Penn-CEIRR</a>, assessed the efficacy of an mRNA-based vaccine targeting the viral surface glycoprotein hemagglutinin. The authors built upon recent advances in mRNA technology used in current COVID-19 vaccines to deliver more antigens at once than what is feasible through other approaches. Twenty unique mRNAs encoding hemagglutinins from the 18 known influenza A subtypes and two influenza B lineages were encapsulated in a lipid nanoparticle system and administered to mice and ferrets. The multivalent mRNA vaccine was highly effective at stimulating cross-reactive and subtype-specific antibodies in both mice and ferrets and protected animals from severe illness following infection with strains both like and unlike those used to produce the vaccine.&nbsp;By incorporating 20 diverse antigens into a single vaccine, investigators elicited broad protection absent of the viral mismatch limitations currently hindering seasonal flu vaccines. This work advances development of a “universal” influenza vaccine to defend against seasonal and pandemic flu. To read more about this study, check out the <a href="https://directorsblog.nih.gov/2022/12/06/experimental-mrna-vaccine-may-protect-against-all-20-influenza-virus-subtypes/" target="_blank" rel="noopener noreferrer">NIH Director’s Blog</a> and <a href="https://www.pennmedicine.org/news/news-releases/2022/november/penn-develops-mrna-flu-vaccine" target="_blank" rel="noopener noreferrer">Penn Medicine News</a>. To read the full article, <a href="https://www.science.org/doi/10.1126/science.abm0271?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%20%200pubmed" target="_blank" rel="noopener noreferrer">click here</a>.&nbsp;<a href="https://www.science.org/doi/10.1126/science.abm0271" target="_blank" rel="noopener noreferrer">Arevalo, CP et al. (2022) A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. 378: 899-904.</a>&nbsp;&nbsp;

Publication Commentary

Penn-CEIRR

Researchers from Penn-CEIRR developed an mRNA-lipid nanoparticle vaccine incorporating hemagglutinin antigens from 20 different influenza subtypes

Graphical depiction of 20 HA mRNA-lipid nanoparticle vaccine. Image credit: NIH Director's Blog.

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