<figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/Resized_Adobe_Stock_294025271_31dff46810.jpg"><figcaption>Researcher evaluates swine at a farm</figcaption></figure>Penn-CEIRR researchers <a href="https://www.ceirr-network.org/search?keyword=Phillip%20Gauger" target="_blank" rel="noopener noreferrer">Phillip Gauger, D.V.M, Ph.D.</a>, <a href="https://www.ceirr-network.org/search?keyword=Amy%20Baker" target="_blank" rel="noopener noreferrer">Amy Baker, D.V.M., Ph.D.</a>, and colleagues recently investigated the presence of Influenza A Virus (IAV) at the farm level in both swine and in human workers. The results of their active surveillance work were published in <a href="https://www.ceirr-network.org/resources/publications?keyword=Influenza%20a%20Virus%20Detection%20at%20the%20Human-Swine%20Interface%20in%20US%20Midwest%20Swine%20Farms" target="_blank" rel="noopener noreferrer">Viruses</a>. IAV causes significant economic loss for pig producers due primarily to reduced weight gain. IAV is also a potential and continuous threat to public health and has contributed to previous human influenza outbreaks. Swine are unique mixing vessels, able to be infected with both avian and human influenza viruses, making them a population uniquely capable of generating new IAVs. One of the most prominent examples of this effect was the H1N1 pandemic in 2009 which included avian-, swine-, and human-origin strains.Due to swine harboring unique IAV strains with potential to transmit across species, humans that work on swine farms play a critical role in bidirectional transmission dynamics. Past studies have shown that occupational exposure increased farm employees’ risk of IAV infection from swine. As such, the shared environment between swine and humans must be examined at the farm level to better understand the dynamics of IAV at the human-swine interface with an end goal of optimizing surveillance and control strategies.To fill this gap, Penn-CEIRR researchers tested pigs and farm employees at breeding farms and their respective nurseries to assess IAV detection and diversity over time. Farm employees and swine were tested monthly for the presence of IAV, and isolates were sequenced to better understand the strains of IAV present and how IAV clades are evolving. The authors also conducted surveys of farm workers to better understand existing biosecurity and management practices.Among surveyed farm employees, only 29.2% reported receiving the IAV vaccine within the past 12 months, a rate much lower than the reported national average (46.9%). During the monthly active surveillance, IAV was detected in 0.9% of employees when sampled at work. Additionally, three cases of seasonal human IAV were detected in farm employees, but no direct evidence of transmission to swine was observed. Importantly, sequencing revealed the presences of a strain of IAV - H3.1990.4 - that the current vaccine is unlikely to offer protection against.This study reveals that it is essential to include swine and farm employees in influenza surveillance and for said employees to receive routine seasonal influenza vaccination. Additionally, including sequencing in surveillance is critical as it reveals differences between strains present in the vaccine and those present on farms. Identifying gaps in vaccine coverage is necessary to inform appropriate vaccine updates and maintain optimal control of IAV at the farm level.&nbsp;

Commentaries

Penn-CEIRR

Influenza

Surveillance

Using active surveillance, Penn-CEIRR researchers found the presence of Influenza A virus in both pigs and humans underscoring the importance of biosecurity measures at the human-swine interface at the farm level.

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Researchers at Penn-CEIRR Used Active Surveillance to Detect Influenza A and Evaluate Genetic Diversity Over Time at the Farm Level

<figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/Resized_Fluzone_embedded_image_thumbnail_c1f5d2f873.jpg"><figcaption>Nurse places a band-aid on an elderly patient's arm after administration of flu vaccine.</figcaption></figure>A study published in the Journal of Infectious Diseases led by <a href="https://www.ceirr-network.org/centers/cider" target="_blank" rel="noopener noreferrer">CIDER</a> researcher <a href="https://www.ceirr-network.org/search?keyword=Andreas%20Handel" target="_blank" rel="noopener noreferrer">Dr. Andreas Handel</a> and his colleagues aimed to elucidate the vaccine efficacy (VE) of high-dose (HD) Fluzone vaccine in older adults (&gt; 65 years) compared to the standard-dose (SD) in older and younger adults (&lt; 65 years). Older adults are at a particular risk for severe influenza infections and death due to the decline of the immune system function as we age. To combat this, older adults are given HD vaccines, which are associated with improved immune responses and clinical outcomes in those &gt; 65 years, compared to SD vaccines.Fluzone HD is one of the vaccines the Centers for Disease Control and Prevention recommends for older adults. Studies show that Fluzone HD is associated with reduced risk of influenza-like illness, increased hemagglutination inhibition (HAI) titers, and protection against laboratory confirmed influenza. Although these and other studies have shown improvements in outcomes for those who have received Fluzone HD, HD vaccine formulations are often limited to two to three influenza seasons. Recurring changes to vaccine components minimizes the overall understanding of VE – a key metric for vaccine quality.VE can be measured directly using traditional endpoints of observational studies and clinical trials, but these types of studies are not only costly, but time consuming. As such, influenza researchers – such as those at CIDER – are leveraging immunogenicity data, which are easier to measure and more readily available. HAI titer, used in this study, is an already established correlate of protection that can be used to estimate VE more efficiently.In this study, CIDER researchers assessed HAI titers from a human vaccine cohort that received either SD or HD Fluzone vaccines across nine influenza seasons from 2013-2022 using a previously developed statistical model based on a meta-analysis of observational studies, clinical trials, and challenge studies. Participants were defined as being part of one of three groups: &lt; 65 years of age who received SD vaccines, &gt; 65 years of age who received the SD vaccine, &gt; 65 years of age who received the HD vaccine.As expected, the HD vaccine generally improved the estimated VE in older adults compared to the SD. However, HD recipients often demonstrated a lower estimated VE compared to younger adults who received the SD vaccine. These results indicate that while HD vaccines are more protective than SD vaccines in older adults, the impact is not large, and older adults still rarely reach the level of protection seen in younger adults.While age is a non-modifiable factor, conducting this study was important to better understand vaccine responses between older adults receiving HD vaccines and younger adults receiving SD vaccines as this comparison has not been previously established. These analyses highlight opportunities for further improvement of vaccines in older adults, including increasing dosage or addition of adjuvants, and other formulation changes that may offer additional protection.To read the full article, go to:<ol style="list-style-type:decimal;"><li><a href="https://pubmed.ncbi.nlm.nih.gov/39670611/" target="_blank" rel="noopener noreferrer">Hammerton et al. (2025) Estimating Standard-Dose and High-Dose Fluzone Vaccine Efficacies for Influenza A Based on Hemagglutination Inhibition Titers. JID. 231:5</a></li></ol>

CIDER

Vaccine

CIDER researchers found that while the high-dose Fluzone vaccine increases protection in older adults, it does not reach the level of protection afforded to younger adults.

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CIDER Researchers Compare Standard-dose and High-dose Fluzone Influenza Vaccines to Better Understand Efficacy in Older Adults Compared to Younger Adults   

<figure class="image image-style-align-right"><a href="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/Johns+Hopkins+CEIRR+(JH-CEIRR).pdf" target="_blank" rel="noopener noreferrer" download="download"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/Johns_Hopkins_CEIRR_JH_CEIRR_f870cbda0d.png"></a><figcaption>JH-CEIRR Infobyte highlighting the Center’s major research areas and unique methodologies. To view a full-size PDF version, click the image above.</figcaption></figure>The CEIRR Network studies the natural history, transmission, and pathogenesis of influenza and other respiratory viruses that have the potential to cause seasonal disease and potentially new outbreaks. The seven multidisciplinary and collaborative research Centers provide an international research infrastructure to address respiratory viral outbreaks. One such Center, the Johns Hopkins University CEIRR (<a href="https://www.ceirr-network.org/centers/jh-ceirr" target="_blank" rel="noopener noreferrer">JH-CEIRR</a>), operates a research pipeline integrating respiratory virus surveillance, virus isolation and characterization, immunological responses to vaccination and infection, and disease diagnostics development. Under the leadership of <a href="https://www.ceirr-network.org/search?keyword=Andrew%20Pekosz" target="_blank" rel="noopener noreferrer">Andrew Pekosz, Ph.D.</a> and <a href="https://www.ceirr-network.org/search?keyword=Richard%20Rothman" target="_blank" rel="noopener noreferrer">Richard Rothman, M.D., Ph.D.</a>, both at Johns Hopkins University, JH-CEIRR’s studies cover four major themes:&nbsp;<ol style="list-style-type:decimal;"><li>Virus Surveillance and Isolation&nbsp;</li><li>Antigenic Evolution and Fitness&nbsp;</li><li>Variations in Immune Response&nbsp;</li><li>Computational Analysis of Disease&nbsp;</li></ol>Dr. Pekosz was recruited to Johns Hopkins University by the late Diane Griffin, M.D., Ph.D., in part to establish an influenza research presence at the university. In parallel, Dr. Rothman was working on diagnostics for infectious diseases with a biodefense program. At the behest of Dr. Griffin, Drs. Pekosz and Rothman began discussing opportunities to continue studying influenza and developing diagnostics. Drawing on Dr. Rothman’s clinical and diagnostic experience and Dr. Pekosz’s &nbsp;basic science and public health expertise, they began strategizing on a pipeline to better understand and respond to seasonal influenza. The two identified additional investigators to join the effort and eventually secured funding from the National Institute of Allergy and Infectious Diseases (NIAID) to form JH-CEIRR, which was originally called <a href="https://www.ceirr-network.org/about/the-legacy-of-ceirs/ceirs-center-archive#:~:text=Johns%20Hopkins%20Center%20of%20Excellence%20for%20Influenza%20Research%20and%20Surveillance" target="_blank" rel="noopener noreferrer" download="download">JH-CEIRS</a> under the original <a href="https://www.ceirr-network.org/about/the-legacy-of-ceirs/ceirs-center-archive" target="_blank" rel="noopener noreferrer" download="download">CEIRS</a> contract.&nbsp;When asked about JH-CEIRR’s scientific aims, Dr. Pekosz took a step back to emphasize that “influenza is more than a bad cold… it causes tens of thousands of deaths a year and hundreds of thousands of hospitalizations every year in the US alone.” JH-CEIRR researchers aim to drastically reduce these negative health impacts of influenza by:&nbsp;<ol style="list-style-type:decimal;"><li>Improving diagnostic tools to detect the virus earlier&nbsp;</li><li>Identifying factors in individuals that increase their risk of developing severe disease&nbsp;</li><li>Determining how to boost immune responses after vaccination&nbsp;</li><li>Predicting if an emerging influenza strain strengthened its replication fitness and thereby increased its ability to infect or cause disease&nbsp;</li></ol>The Center’s collaborative approach combines scientific, clinical, and public health analyses to improve how local, national, and global organizations prepare for and respond to influenza viruses seasonally and during outbreaks.&nbsp;Today, JH-CEIRR’s research pipeline is comprised of more than 15 investigators and has generated over <a href="https://www.ceirr-network.org/resources/publications?keyword=(Center)%20JH-CEIRR" target="_blank" rel="noopener noreferrer">35 publications</a> on the evolution and pathogenesis of influenza, variations in immune responses to influenza infection and vaccination, and improving diagnostics. A unique strength of JH-CEIRR’s pipeline focuses on computational analysis using artificial intelligence (AI) and machine learning (ML) to study host factors that affect disease severity and immune responses. Dr. Pekosz shared that he’s particularly excited by JH-CEIRR’s investigators’ ability to “identify virus mutations or recombination events that impact disease severity and spread in the population.” He’s fascinated by how an influenza virus changes a basic trait, like its ability to replicate or form a plaque in the lab, and is simultaneously able to evade pre-existing immune responses, which ultimately results in a viral strain that may cause more infections or more severe disease in a population.<figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/JH_CEIRR_PI_headshot_Richard_Rothman_300x302_190738de0e.png"><figcaption>Co-principal Investigator of JH-CEIRR, Richard Rothman, M.D., Ph.D., Johns Hopkins University</figcaption></figure><figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/JH_CEIRR_PI_headshot_Andrew_Pekosz_300x301_0a4406ec30.png"><figcaption>Principal Investigator of JH-CEIRR, Andrew Pekosz, Ph.D., Johns Hopkins University</figcaption></figure>Looking forward, Dr. Pekosz is interested in an expansion of CEIRR’s research efforts applied to all respiratory viruses. He envisions a future where the field leverages their expertise on influenza to study other respiratory viruses, especially those that have the potential to cause new outbreaks. From his view, “we have the skillsets in the Network to make a difference with all respiratory virus infections, not just influenza.”&nbsp;The iDPCC interviewed Dr. Andrew Pekosz to learn more about his experiences:&nbsp;1. Who/what inspired you to go into science in general?It was really about having great high school teachers – both science and non-science – who encouraged me to use logic and reason to solve problems. That led me to focus in on science research and when I found a great virology lab as an undergraduate, I was hooked for life.&nbsp;2. What is one thing on your bucket list?&nbsp;To sing in a Broadway musical.&nbsp;3. How has your career trajectory changed over time?&nbsp;I’ve been very fortunate to have a pretty straightforward career trajectory. At every stage of my career and education, I focused in on what I loved to do and tried to find the best places to do that.&nbsp;4. Do you have advice for early career scientists on career longevity in research?It all starts with loving what you do. You then just have to follow the virus and it will continually show you interesting and important things you should investigate.&nbsp;5. Do you have any hobbies or special interests that you'd like to share?I tend to obsess about Premier League Soccer (its actually Football) and Japanese giant monster movies (think Godzilla).&nbsp;6. What is your favorite conference that you attended?The Negative Strand RNA Virus Conference is always great – a perfect mix of science and socializing.&nbsp;7. What is your favorite country to attend a conference… or a vacation?&nbsp;I love visiting England and always combine both when I’m there.&nbsp;8. Are you a morning person or a night person?&nbsp;Both! Sleep is overrated…&nbsp;

Spotlight

JH-CEIRR

Infobyte

Principal investigators, Drs. Andrew Pekosz and Richard Rothman, recount the origin of JH-CEIRR, describe its research pipeline, and envision a future tackling more respiratory viral infections.&nbsp;

JH-CEIRR Infobyte highlighting the Center’s major research areas and unique methodologies. To view a full-size PDF version, click the image above.

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Johns Hopkins University CEIRR (JH-CEIRR)

<figure class="image image-style-align-right"><a href="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/University+of+Pennsylvania+CEIRR+(Penn-CEIRR).pdf" target="_blank" rel="noopener noreferrer" download="download"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/University_of_Pennsylvania_CEIRR_Penn_CEIRR_c9735aec8b.png"></a><figcaption>Penn-CEIRR Infobyte highlighting key areas of research and approaches. To view a full-size PDF version, click the image above.</figcaption></figure>The CEIRR Network is composed of seven multidisciplinary and collaborative research Centers focused on unraveling influenza virus transmission, pathogenicity, and ecology to support public health and mitigate the impact of influenza infection. University of Pennsylvania CEIRR (<a href="https://www.ceirr-network.org/centers/penn-ceirr" target="_blank" rel="noopener noreferrer">Penn-CEIRR</a>) contributes to this mission through its specialization in longitudinal human studies, viral surveillance, immunology, and computational modeling to better understand immune responses to influenza vaccination and infection and the risks posed by emerging flu strains. Headed by <a href="https://www.ceirr-network.org/search?keyword=Scott%20Hensley" target="_blank" rel="noopener noreferrer">Scott Hensley, Ph.D.</a> of the University of Pennsylvania, and in collaboration with institutions across the United States, Asia, and the United Kingdom, Penn-CEIRR drives research in three key areas that contribute to a deeper understanding of influenza virus evolution and immunity:&nbsp;<ol style="list-style-type:decimal;"><li>Longitudinal Human Studies&nbsp;</li><li>Risk Assessment&nbsp;</li><li>Computational Modeling Core</li></ol>The story of Penn-CEIRR is rooted in collaboration. When assembling his research group 15 years ago, Dr. Hensley says he dreamed of running a CEIRR Center. He found many of his research goals aligned with CEIRR’s (then <a href="https://www.ceirr-network.org/about/the-legacy-of-ceirs" target="_blank" rel="noopener noreferrer">CEIRS</a>) mission and established strong, enduring partnerships to answer them. Today, many PIs within Penn-CEIRR are collaborators from his days as an Assistant Professor. With over 35 investigators across more than 20 institutions Dr. Hensley says, “I think we assembled a terrific group of creative researchers that work well with each other.”Penn-CEIRR combines experimental and computational methods to better understand the epidemiology, immunology, and evolutionary biology of influenza viruses. This includes collecting data from over 10 clinical studies, including longitudinal human cohorts, to evaluate viral transmission within households and communities, analyze individual influenza immunity, and isolate and characterize human-derived influenza viruses. Additionally, Penn-CEIRR surveils influenza viruses from swine and birds to inform risk assessments and response strategies. The Penn-CEIRR has a strong computational program that integrates data generated throughout the CEIRR network. The marriage of these approaches enables Penn-CEIRR to:&nbsp;<ol style="list-style-type:decimal;"><li>Evaluate antigenic drift of influenza viruses&nbsp;</li><li>Assess immunity against emerging influenza virus strains&nbsp;</li><li>Understand how childhood exposure to influenza viruses shapes immune responses to seasonal and emerging strains later in life&nbsp;</li><li>Characterize variation in immune responses to influenza vaccination&nbsp;</li><li>Develop new influenza vaccine strategies and platforms&nbsp;</li></ol>To date, Penn-CEIRR has generated over <a href="https://www.ceirr-network.org/resources/publications" target="_blank" rel="noopener noreferrer">145 publications</a> and <a href="https://app.ceirr-network.org/search" target="_blank" rel="noopener noreferrer">6,100 influenza genomic sequences</a>.The utility of these approaches is demonstrated by Penn-CEIRR's recent efforts to respond to new, antigenically drifted subclade K H3N2 viruses that have been circulating in humans. Using a combination of methods including high-throughput neutralization assays, serology techniques, and electron microscopy-based polyclonal epitope mapping (EMPEM), Penn-CEIRR successfully characterized the specificity of immune responses to these antigenically drifted viruses to enable effective influenza infection mitigation. As Dr. Hensley says, “Near real-time assessment of antigenically drifted strains is critical for choosing effective vaccine strains for upcoming influenza seasons.”&nbsp;<figure class="image image-style-align-right"><img src="https://ceirr-public-website-static-prod.s3.us-east-1.amazonaws.com/Scott_Hensley_Image_resized_b1d4d1f558.png"><figcaption>Principal Investigator of Penn-CEIRR, Scott Hensley, Ph.D., University of Pennsylvania</figcaption></figure>Looking toward the future, Dr. Hensley believes ongoing collaboration will be key for the continued success of the CEIRR Program, stating “CEIRR has a terrific network of scientists that can respond to any emerging threat, such as a new drifted H3N2 variant or an entirely new subtype that infects livestock leading to human infections. It is critical for CEIRR to foster collaborations between scientists with diverse interests so that we can continue our mission of decreasing the toll caused by influenza virus infections.”&nbsp;The iDPCC interviewed Dr. Scott Hensley to learn more about his experiences:&nbsp;1. Who/what inspired you to go into science in general?I thought that I was going to be a professional basketball player up to ~18 years of age, at which point I realized I wasn’t very fast or tall, and I couldn’t jump high. I didn’t consider science until a bit later in life, but after I worked in a lab as an undergraduate I became hooked.&nbsp;2. Do you have advice for early career scientists on career longevity in research?Have fun and pursue questions that you think are interesting.&nbsp;3. Do you have any hobbies or special interests that you'd like to share?&nbsp;I like playing tennis and coaching my son and daughter’s basketball teams.&nbsp;4. What is your favorite country to attend a conference… or a vacation?Spain5. Are you a morning person or a night person?Night

Principal Investigator, Dr. Scott Hensley, describes the collaborative research performed by Penn-CEIRR to better understand influenza virus evolution and susceptibility through virological, immunological, and computational modeling approaches.&nbsp;

Penn-CEIRR Infobyte highlighting key areas of research and approaches. To view a full-size PDF version, click the image above. 

CEIRR

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