In Egypt, efforts to control highly pathogenic H5N1 avian influenza virus in poultry and in humans have failed despite increased biosecurity, quarantine, and vaccination at poultry farms. The ongoing circulation of HP H5N1 avian influenza in Egypt has caused >100 human infections and remains an unresolved threat to veterinary and public health. Here, we describe that the failure of commercially available H5 poultry vaccines in Egypt may be caused in part by the passive transfer of maternal H5N1 antibodies to chicks, inhibiting their immune response to vaccination. We propose that the induction of a protective immune response to H5N1 is suppressed for an extended period in young chickens. This issue, among others, must be resolved and additional steps must be taken before the outbreaks in Egypt can be controlled.

Since the reemergence of highly pathogenic H5N1 influenza viruses in humans in 2003, these viruses have spread throughout avian species in Asia, Europe, and Africa. Their sustained circulation has resulted in the evolution of phylogenetically diverse lineages. Viruses from these lineages show considerable antigenic variation, which has confounded vaccine planning efforts. We reconstructed ancestral protein sequences at several nodes of the hemagglutinin (HA) and neuraminidase (NA) gene phylogenies that represent ancestors to diverse H5N1 virus clades. By using the same methods that have been used to generate currently licensed inactivated H5N1 vaccines, we were able to produce a panel of replication competent influenza viruses containing synthesized HA and NA genes representing the reconstructed ancestral proteins. We identified two of these viruses that showed promising in vitro cross-reactivity with clade 1, 2.1, 2.2, 2.3.4, and 4 viruses. To confirm that vaccine antigens derived from these viruses were able to elicit functional antibodies following immunization, we created whole-virus vaccines and compared their protective efficacy versus that of antigens from positive control, naturally occurring, and broadly reactive H5N1 viruses. The ancestral viruses’ vaccines provided robust protection against morbidity and mortality in ferrets challenged with H5N1 strains from clades 1, 2.1, and 2.2 in a manner similar to those based on the control strains. These findings provide proof of principle that viable, computationally derived vaccine seed viruses can be constructed within the context of currently licensed vaccine platforms. Such technologies should be explored to enhance the cross reactivity and availability of H5N1 influenza vaccines.

Pre-existing antibodies to the hemagglutinin of pandemic A (H1N1) 2009 influenza virus (pH1N1) positively correlates with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pH1N1 proteins is unknown. We measured serum antibodies to the neuraminidase of pandemic H1N1 (pNA) in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pNA were observed in all age groups; however, vaccination elevated pNA antibodies in predominately the elderly. Therefore, contemporary seasonal vaccines likely contribute to reduction of pH1N1 associated disease in older individuals.

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Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific IMPORTANCEHighly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. The variability of the virus means that such an approach must be broad spectrum. To achieve this, we developed two antibodies that neutralize H5N1 influenza viruses. In mice, these antibodies provided complete protection against a spectrum of H5N1 influenza viruses at a single low dose. We then combined the two antibodies into a single molecule, FcDART, which combined the broad-spectrum activity and protective efficacy of both antibodies. This treatment provides a novel and effective therapeutic agent or prophylactic with activity against highly pathogenic H5N1 avian influenza viruses.

BACKGROUND: Modern electronic health record systems (EHRS) reportedly offer advantages including improved quality, error prevention, cost reduction, and increased efficiency. This project reviewed the impact on specimen turnaround times (TAT) and percent compliance for specimens processed in a STAT laboratory after implementation of an upgraded EHRS. METHODS: Before EHRS implementation, laboratory personnel received instruction and training for specimen processing. One laboratory member per shift received additional training. TAT and percent compliance data sampling occurred 4 times monthly for 13 months post-conversion and were compared with the mean of data collected for 3 months pre-conversion. Percent compliance was gauged using a benchmark of reporting 95% of all specimens within 7 min from receipt. RESULTS: Control charts were constructed for TAT and percent compliance with control limits set at 2 SD and applied continuously through the data collection period. TAT recovered to pre-conversion levels by the 6th month post-conversion. Percent compliance consistently returned to pre-conversion levels by the 10th month post-conversion. Statistical analyses revealed the TAT were significantly longer for 3 months post-conversion (P < .001) compared with pre-conversion levels. Statistical significance was not observed for subsequent groups. Percent compliance results were significantly lower for 6 months post-conversion (P < .001). Statistical significance was not observed for subsequent groups. CONCLUSIONS: Extensive efforts were made to train and prepare personnel for challenges expected after the EHRS upgrade. Specific causes identified with the upgraded EHRS included multiple issues involving personnel and the EHRS. These data suggest that system and user issues contributed to delays in returning to pre-conversion TAT and percent compliance levels following the upgrade in the EHRS.

Academic medical centers comprise a diverse group of students, researchers, and health care professionals. There are also 3 unique environments: education, health care, and research. Differences in biosafety practices and procedures exist between these environments, but the common goal is to produce well-trained and successful health care and research professionals. An important part of the educational experience should include biosafety training. Having a strong foundation on biosafety principles will increase safety compliance in both the clinical and research workforces. Both students and employees should be knowledgeable and aware of biosafety. A biosafety survey was developed to measure the knowledge of students on biosafety principles at an academic medical center. This survey was validated by field professionals, including physicians, nurses, laboratory technologists, and researchers, who were surrogates for a multidisciplinary student population. The goal of the validation was to determine if the biosafety survey included appropriate questions and responses to adequately assess biosafety knowledge among students at an academic medical center. This step was very important because there are differences in the practices and guidelines for health care and research arenas. The validation results indicated that there are differences in the understanding of biosafety principles among different disciplines. There are also major differences in interpretations of biosafety principles between clinicians and researchers.