A National Public Health Agenda for Osteoarthritis: 2020 Update (OA Agenda) states, “We envision a nation in which adults with osteoarthritis (OA) are able to live full lives with less pain, stiffness, and disability; greater mobility; and preserved function and independence.”1 OA affects more than 528 million or 7% of people worldwide, and 32.5 million or 1 in 7 adults in the United States (US).1, 2 Countries with established market economies, older adult populations, and populations with high rates of obesity may have higher prevalence.2

Keeping the global food supply safe necessitates international collaborations between countries. Health and regulatory agencies routinely communicate during foodborne illness outbreaks, allowing partners to share investigational evidence. A 2016-2020 outbreak of Listeria monocytogenes infections linked to imported enoki mushrooms required a multinational collaborative investigation among the United States, Canada, Australia, and France. Ultimately, this outbreak included 48 ill people, 36 in the United States and 12 in Canada, and was linked to enoki mushrooms sourced from one manufacturer located in the Republic of Korea. Epidemiologic, laboratory, and traceback evidence led to multiple regulatory actions, including extensive voluntary recalls by three firms in the United States and one firm in Canada. In the United States and Canada, the Korean manufacturer was placed on import alert while other international partners provided information about their respective investigations and advised the public not to eat the recalled enoki mushrooms. The breadth of the geographic distribution of this outbreak emphasizes the global reach of the food industry. This investigation provides a powerful example of the impact of national and international coordination of efforts to respond to foodborne illness outbreaks and protect consumers. It also demonstrates the importance of fast international data sharing and collaboration in identifying and stopping foodborne outbreaks in the global community. Additionally, it is a meaningful example of the importance of food sampling, testing, and integration of sequencing results into surveillance databases.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

In the original article, there was a mistake in Figure 1 and Figure 2 as published. The graphics used are different than those originally submitted.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.(§) Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox(¶) during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy(††) in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.(§§) Engaging all persons with HIV in sustained care remains a critical public health priority.

Listeriosis is a serious infection usually caused by eating food contaminated with the bacterium Listeria monocytogenes. An estimated 1,600 persons become ill with listeriosis each year, among whom approximately 260 die. Persons at higher risk for listeriosis include pregnant persons and their newborns, adults aged ≥65 years, and persons with weakened immune systems. Persons with invasive listeriosis usually report symptoms starting 1-4 weeks after eating food contaminated with L. monocytogenes; however, some persons who become infected have reported symptoms starting as late as 70 days after exposure or as early as the same day of exposure (1). On January 29, 2021, PulseNet, the national molecular subtyping surveillance network coordinated by CDC, identified a multistate cluster of three L. monocytogenes infections: two from Maryland and one from Connecticut (2). CDC, the Food and Drug Administration (FDA), and state and local partners began an investigation on February 1, 2021. A total of 13 outbreak-related cases were eventually identified from four states. All patients reported Hispanic ethnicity; 12 patients were hospitalized, and one died. Rapid food testing and record collection by regulatory agencies enabled investigators to identify a brand of queso fresco made with pasteurized milk as the likely source of the outbreak, leading to an initial product recall on February 19, 2021. Fresh, soft Hispanic-style cheeses made with pasteurized milk are a well-documented source of listeriosis outbreaks. These cheeses can be contaminated with L. monocytogenes unless stringent hygienic controls are implemented, and the processing environment is monitored for contamination (3). U.S. public health agencies should establish or improve communications, including new methods of disseminating information that also effectively reach Hispanic populations, to emphasize the risk from eating fresh, soft Hispanic-style cheeses, even those made with pasteurized milk.

A 27-year-old female white-faced saki (Pithecia pithecia) died following an onset of vomiting and ptyalism. Necropsy revealed lesions of suppurative ventriculitis, choroid plexitis, periventricular encephalitis and meningitis with intralesional gram-positive coccobacilli and paired rods. The saki also had suppurative to mononuclear hepatitis, mild intestinal crypt necrosis, proliferative glomerulonephritis, aortic arteriosclerosis, pulmonary interstitial fibrosis, chronic mild epicarditis, ovarian medullary arteriopathy and a focal superficial cerebral fibrotic nodule with surrounding chronic mixed cell inflammation. Listeria monocytogenes was cultured from liver and spinal cord. Intralesional Listeria bacteria were immunolabelled in brain sections and real-time polymerase chain reaction of brain tissue detected L. monocytogenes. Whole genome multilocus sequence typing characterized the cultured bacterial isolates as sequence type 6 and clonal complex 6. A database search for related clinical and food listerial outbreaks identified genetically related isolates but, because these isolates were more than 20 alleles distant from the saki isolates, they were not a related cluster. Reports of listeriosis in non-human primates are infrequent, and when infections do occur, they tend to be haematogenous with the propensity to cause meningoencephalitis. This saki likely ingested environmental L. monocytogenes, which resulted in disease that may have been facilitated by pre-existing co-morbidities and age. © 2022 Elsevier Ltd

Heart failure (HF) is a leading global public health problem with >64 million prevalent cases globally. Patients with HF with reduced ejection fraction (HFrEF) from low- and middle-income countries experience a 22% to 58% higher 1-year mortality rate than those in high-income countries.1 Guideline-directed medical therapy (GDMT) consisting of ACE (angiotensin-converting enzyme) inhibitors or ARB (angiotensin receptor blockers) or ARNI (angiotensin receptor-neprilysin inhibitors), -blockers, MRA (mineralocorticoid receptor antagonists), and SGLT2 (sodium-glucose cotransporter 2) inhibitors substantially reduces mortality among patients with HFrEF. These medicines are among the most cost-effective interventions and are thus included as the highest priority health system interventions recommended by the Disease Control Priorities Project.2 Despite this high-quality evidence, GDMT remains widely underutilized in low- and middle-income countries resulting in widespread undertreatment of patients with HFrEF due to health system-, provider-, and patient-level barriers.1 National essential medicines lists (EMLs) promoted by the World Health Organization (WHO) guide countries on which medications to purchase in the setting of limited resources and have resulted in higher procurement and availability of essential medicines in the public sector.3 We provide a cross-sectional analysis of national EMLs in 53 low- and middle-income countries, and availability, price, and affordability of GDMT in select countries to identify potential barriers to access to these essential medicines for patients with HFrEF.

Our globalised food supply presents immense challenges to ensuring food safety, as shown by outbreaks of foodborne illnesses associated with imported foods.1 The speed with which such outbreaks are resolved often depends on how rapidly public health scientists communicate and disseminate actionable data. One such data source is whole-genome sequencing, which is the newest method of molecular subtyping and has superior discriminatory power compared with previous methods.2 Consequently, whole-genome sequencing has been and continues to be adopted by countries across the world as a tool to combat foodborne pathogens.3 Sequence data can be made publicly available through numerous databases (eg, the European Nucleotide Archive, the National Center for Biotechnology Information [NCBI] Sequence Read Archive, and the DNA Data Bank of Japan Sequence Read Archive). Laboratories are encouraged to share the genomes they have sequenced4 and, as new genomes are made public, isolates can be clustered into genetically similar groups to facilitate the detection of potential outbreaks and sources of contamination.

Outbreaks of Listeria monocytogenes (L. monocytogenes) infections have historically been associated with contaminated deli meats, but recent outbreaks have been linked to produce. To date, avocados have not been identified as the source of any outbreaks of L. monocytogenes infections in the United States, but avocado samples have yielded strains that were closely related genetically to clinical L. monocytogenes isolates. To determine whether avocados have been a source of listeriosis, we conducted a retrospective review of epidemiological data for clinical isolates that were genetically related to isolates from avocados. Using a national database, we identified clusters containing clinical and at least one avocado isolate. We then selected clusters based upon isolation dates, cluster and composition size, and available food history data. For each cluster, we assessed whether (1) avocado consumption was higher among case-patients in the cluster than among those with sporadic illnesses, and (2) whether the only food isolates within the cluster were from avocados. If both conditions were met, the link was considered "likely," if one condition was met the link was considered "possible," and if neither condition was met evidence was "limited." Five of fifteen clusters met criteria for assessment. Of these, two were classified as having "limited" evidence for a link to avocados, two as "possible," and one as "likely." For the cluster considered "likely", avocado consumption was significantly higher among case-patients in the cluster compared to sporadic illnesses (Odds ratio: 8.5, 95% CI 1.5-86.5). We identified three clusters that were likely or possibly linked to avocados, suggesting avocados could be a source of listeriosis in the United States. Messaging on safe handling might be warranted for groups at higher risk, but further research is first needed to better characterize the ecology of pathogens on avocados and likelihood of internalization of L. monocytogenes.

Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research.

Infections caused by pathogens commonly acquired from consumption of food are not always transmitted by that route. They may also be transmitted through contact to animals, other humans or the environment. Additionally, many outbreaks are associated with food contaminated from these non-food sources. For this reason, such presumed foodborne outbreaks are best investigated through a One Health approach working across human, animal and environmental sectors and disciplines. Outbreak strains or clones that have propagated and continue to evolve in non-human sources and environments often show more sequence variation than observed in typical monoclonal point-source outbreaks. This represents a challenge when using whole genome sequencing (WGS), the new gold standard for molecular surveillance of foodborne pathogens, for outbreak detection and investigation. In this review, using recent examples from outbreaks investigated in the United States (US) some aspects of One Health approaches that have been used successfully to solve such outbreaks are presented. These include using different combinations of flexible WGS based case definition, efficient epidemiological follow-up, traceback, surveillance, and testing of potential food and environmental sources and animal hosts.

On December 1, 2017, PulseNet, CDC’s molecular subtyping network for foodborne disease surveillance, identified a cluster of three Listeria monocytogenes clinical isolates with indistinguishable pulsed-field gel electrophoresis (PFGE) pattern combinations. These isolates were closely related to one another by whole-genome multilocus sequence typing within three allele differences (range = 0–3 alleles), indicating that the infections were likely from the same source. CDC, the Food and Drug Administration (FDA), and state and local health departments initiated a multistate investigation. An outbreak case of listeriosis was defined as an infection with L. monocytogenes, with an isolate that was indistinguishable by PFGE and closely related by whole-genome multilocus sequence typing to the outbreak strain isolated during October–December 2017.

In June 2017, PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified 17 Salmonella Agbeni clinical isolates with indistinguishable XbaI enzyme pattern (outbreak strain) by pulsed-field gel electrophoresis. The same Salmonella Agbeni XbaI pattern was isolated from a turtle in 2015; in a 2016 investigation involving the same outbreak strain, 63% of patients reported contact with turtles (CDC, unpublished data, 2016). Despite prohibition of sale of small turtles (shell length less <4 inches) in the United States since 1975 (1), illness outbreaks associated with turtle contact continue to occur. Ill persons in previous Salmonella Poona and Salmonella Pomona outbreaks linked to turtles were geographically concentrated in the Southwest region of the United States (2,3). Turtle production is known to be higher in the Southeast region of the country (2). An outbreak investigation by CDC and health departments was initiated to identify the source of the 2017 illness outbreak.

Foodborne salmonellosis causes an estimated 1 million illnesses and 400 deaths annually in the United States (1). In recent years, salmonellosis outbreaks have been caused by foods not typically associated with Salmonella. On May 2, 2017, PulseNet, CDC's national molecular subtyping network for foodborne disease surveillance, identified a cluster of 14 Salmonella Chailey isolates with a rare pulsed-field gel electrophoresis (PFGE) pattern. On May 29, Canadian health officials informed CDC that they were also investigating a cluster of five Salmonella Chailey infections in British Columbia with the same PFGE pattern. Nineteen cases were identified and investigated by CDC, U.S. state health departments, the Public Health Agency of Canada, and the British Columbia Centre for Disease Control. Isolates from all cases were highly related by whole genome sequencing (WGS). Illness onset dates ranged from March 10 to May 7, 2017. Initial interviews revealed that infected persons consumed various fresh foods and shopped at grocery chain A; focused questionnaires identified precut coconut pieces from grocery chain A as a common vehicle. The Canadian Food Inspection Agency (CFIA) and the U.S. Food and Drug Administration (FDA) conducted a traceback investigation that implicated a single lot of frozen, precut coconut as the outbreak source. Grocery chain A voluntarily removed precut coconut pieces from their stores. This action likely limited the size and scope of this outbreak.

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes-the leading causes of mortality-through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the "ABCS" (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk" by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model.

The Million Hearts Initiative has a goal of preventing 1 million heart attacks and strokes-the leading causes of mortality-through several public health and healthcare strategies by 2017. The American Heart Association and American College of Cardiology support the program. The Cardiovascular Risk Reduction Model was developed by Million Hearts and the Center for Medicare & Medicaid Services as a strategy to assess a value-based payment approach toward reduction in 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) by implementing cardiovascular preventive strategies to manage the "ABCS" (aspirin therapy in appropriate patients, blood pressure control, cholesterol management, and smoking cessation). The purpose of this special report is to describe the development and intended use of the Million Hearts Longitudinal ASCVD Risk Assessment Tool. The Million Hearts Tool reinforces and builds on the "2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk" by allowing clinicians to estimate baseline and updated 10-year ASCVD risk estimates for primary prevention patients adhering to the appropriate ABCS over time, alone or in combination. The tool provides updated risk estimates based on evidence from high-quality systematic reviews and meta-analyses of the ABCS therapies. This novel approach to personalized estimation of benefits from risk-reducing therapies in primary prevention may help target therapies to those in whom they will provide the greatest benefit, and serves as the basis for a Center for Medicare & Medicaid Services program designed to evaluate the Million Hearts Cardiovascular Risk Reduction Model.

BACKGROUND: This study was conducted to examine the association between ideal cardiovascular health (CVH) and health-related quality of life and health status indicators. METHODS: This cross-sectional study included adult NHANES participants from 2001 to 2010 without CVD (N = 7115). CVH was defined according to AHA definitions with poor, intermediate and ideal levels of the seven factors (diet, BMI, physical activity, smoking, blood pressure, glucose, and cholesterol) assigned scores of 0, 1, and 2, respectively. A CVH score (CVHS) was calculated as the sum of the scores from each individual health factor (range 0-14; higher score indicating greater CVH). CVHS was categorized as poor (0-7), intermediate (8-10), and ideal (11-14). Linear regression models examined the association between CVHS category with health status and number of unhealthy days per month, adjusted for socio-demographic characteristics and disability. RESULTS: Among US adults 20-79 years, 14, 46 and 40 % had ideal, intermediate and poor CVHS, respectively. Compared to those with poor CVH, individuals in intermediate and ideal CVH were 44 and 71 % less likely to report being in fair/poor health. Participants with ideal CVH scores reported a mean of 2.4 fewer unhealthy days over the past month, including one less day in which their physical health was not good and two fewer days in which their mental health was not good. CONCLUSIONS: Ideal CVH is associated with greater overall health status and fewer physically and mentally unhealthy days.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a critical resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best available national data on heart disease, stroke, and other cardiovascular disease–related morbidity and mortality and the risks, quality of care, use of medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions. In 2012 alone, the various Statistical Updates were cited ≈3500 times (data from Google Scholar). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled. | | For this year’s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year. This year’s edition includes a new chapter on peripheral artery disease, as well as new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA’s 2020 Impact Goals. Below are a few highlights from this year’s Update.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on heart disease, stroke, and other cardiovascular disease–related morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions. In 2011 alone, the various Statistical Updates were cited ≈1500 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled. | For this year’s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year. This year’s edition also implements a new chapter organization to reflect the spectrum of cardiovascular health behaviors and health factors and risks, as well as subsequent complicating conditions, disease states, and outcomes. Also, the 2013 Statistical Update contains new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA’s 2020 Impact Goals. Below are a few highlights from this year’s Update.

BACKGROUND: The American Heart Association's 2020 Strategic Impact Goals target a 20% relative improvement in overall cardiovascular health with the use of 4 health behavior (smoking, diet, physical activity, body mass) and 3 health factor (plasma glucose, cholesterol, blood pressure) metrics. We sought to define current trends and forward projections to 2020 in cardiovascular health. METHODS AND RESULTS: We included 35,059 cardiovascular disease-free adults (aged ≥20 years) from the National Health and Nutrition Examination Survey 1988-1994 and subsequent 2-year cycles during 1999-2008. We calculated population prevalence of poor, intermediate, and ideal health behaviors and factors and also computed a composite, individual-level Cardiovascular Health Score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total range, 0-14 points). Prevalence of current and former smoking, hypercholesterolemia, and hypertension declined, whereas prevalence of obesity and dysglycemia increased through 2008. Physical activity levels and low diet quality scores changed minimally. Projections to 2020 suggest that obesity and impaired fasting glucose/diabetes mellitus could increase to affect 43% and 77% of US men and 42% and 53% of US women, respectively. Overall, population-level cardiovascular health is projected to improve by 6% overall by 2020 if current trends continue. Individual-level Cardiovascular Health Score projections to 2020 (men=7.4 [95% confidence interval, 5.7-9.1]; women=8.8 [95% confidence interval, 7.6-9.9]) fall well below the level needed to achieve a 20% improvement (men=9.4; women=10.1). CONCLUSIONS: The American Heart Association 2020 target of improving cardiovascular health by 20% by 2020 will not be reached if current trends continue.

We generated from a single blood sample five independent human mAbs that recognized the Sa antigenic site on the head of influenza hemagglutinin and exhibited inhibitory activity against a broad panel of H1N1 strains. All five Abs used the V(H)3-7 and J(H)6 gene segments, but at least four independent clones were identified by junctional analysis. High-throughput sequence analysis of circulating B cells revealed that each of the independent clones were members of complex phylogenetic lineages that had diversified widely using a pattern of progressive diversification through somatic mutation. Unexpectedly, B cells encoding multiple diverging lineages of these clones, including many containing very few mutations in the Ab genes, persisted in the circulation. Conversely, we noted frequent instances of amino acid sequence convergence in the Ag combining sites exhibited by members of independent clones, suggesting a strong selection for optimal binding sites. We suggest that maintenance in circulation of a wide diversity of somatic variants of dominant clones may facilitate recognition of drift variant virus epitopes that occur in rapidly mutating virus Ags, such as influenza hemagglutinin. In fact, these Ab clones recognize an epitope that acquired three glycosylation sites mediating escape from previously isolated human Abs.

The conserved influenza virus hemagglutinin (HA) stem domain elicits cross-reactive antibodies, but epitopes in the globular head typically elicit strain-specific responses because of the hypervariability of this region. We isolated human monoclonal antibody 5J8, which neutralized a broad spectrum of 20th century H1N1 viruses and the 2009 pandemic H1N1 virus. Fine mapping of the interaction unexpectedly revealed a novel epitope between the receptor-binding pocket and the Ca antigenic site on HA. This antibody exposes a new mechanism underlying broad immunity against H1N1 influenza viruses and identifies a conserved epitope that might be incorporated into engineered H1 virus vaccines.

The 2009 A(H1N1) pandemic influenza virus exhibits hemagglutinin protein sequence homology with the 1918 pandemic influenza virus. We found that human monoclonal antibodies recognized the Sa antigenic site on the head domain of both 1918 and 2009 hemagglutinins, a site that is hypervariable due to immune selection. These antibodies exhibited high potency against the 2009 virus in vitro, and one exerted a marked therapeutic effect in vivo.