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Summary Background Influenza viruses cause substantial annual morbidity and mortality globally. Current vaccines protect against influenza only when well matched to the circulating strains. However, antigenic drift can cause considerable mismatches between vaccine and circulating strains, substantially reducing vaccine effectiveness. Moreover, current seasonal vaccines are ineffective against pandemic influenza, and production of a vaccine matched to a newly emerging virus strain takes months. Therefore, there is an unmet medical need for a broadly protective influenza virus vaccine. We aimed to test the ability of chimeric H1 haemagglutinin-based universal influenza virus vaccine candidates to induce broadly cross-reactive antibodies targeting the stalk domain of group 1 haemagglutinin-expressing influenza viruses. Methods We did a randomised, observer-blinded, phase 1 study in healthy adults in two centres in the USA. Participants were randomly assigned to one of three prime–boost, chimeric haemagglutinin-based vaccine regimens or one of two placebo groups. The vaccine regimens included a chimeric H8/1, intranasal, live-attenuated vaccine on day 1 followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine on day 85; the same regimen but with the inactivated vaccine being adjuvanted with AS03; and an AS03-adjuvanted, chimeric H8/1, intramuscular, inactivated vaccine followed by an AS03-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine. In this planned interim analysis, the primary endpoints of reactogenicity and safety were assessed by blinded study group. We also assessed anti-H1 haemagglutinin stalk, anti-H2, anti-H9, and anti-H18 IgG antibody titres and plasmablast and memory B-cell responses in peripheral blood. This trial is registered with ClinicalTrials.gov , number NCT03300050 . Findings Between Oct 10, 2017, and Nov 27, 2017, 65 participants were enrolled and randomly assigned. The adjuvanted inactivated vaccine, but not the live-attenuated vaccine, induced a substantial serum IgG antibody response after the prime immunisation, with a seven times increase in anti-H1 stalk antibody titres on day 29. After boost immunisation, all vaccine regimens induced detectable anti-H1 stalk antibody (2·2–5·6 times induction over baseline), cross-reactive serum IgG antibody, and peripheral blood plasmablast responses. An unsolicited adverse event was reported for 29 (48%) of 61 participants. Solicited local adverse events were reported in 12 (48%) of 25 participants following prime vaccination with intramuscular study product or placebo, in 12 (33%) of 36 after prime immunisation with intranasal study product or placebo, and in 18 (32%) of 56 following booster doses of study product or placebo. Solicited systemic adverse events were reported in 14 (56%) of 25 after prime immunisation with intramuscular study product or placebo, in 22 (61%) of 36 after immunisation with intranasal study product or placebo, and in 21 (38%) of 56 after booster doses of study product or placebo. Disaggregated safety data were not available at the time of this interim analysis. Interpretation The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. This is the first proof-of-principle study to show that high anti-stalk titres can be induced by a rationally designed vaccine in humans and opens up avenues for further development of universal influenza virus vaccines. On the basis of the blinded study group, the vaccine regimens were tolerable and no safety concerns were observed. Funding Bill & Melinda Gates Foundation.

The variety of weapons of mass destruction are intended to create the maximum possible fear, death, destruction, and general terror in the target region or nation, particularly with new and creative ways of using them. An understanding of how these weapons work, the ways they may be used, and the scope of their destruction can contribute to effectively combating their effects. This article examines these weapons—nuclear, electromagnetic pulse, radiological, chemical and biological technologies—as well as policy approaches to defending against them. The development of national programs directed toward the understanding, potential use, and response to weapons of mass destruction by the United States, Japan and the Soviet Union are reviewed and compared, as are the international agreements that have thus far addressed the possible use of such weapons. q 2005 Elsevier Ltd. All rights reserved.

The normative approach to defining an ethic of a field, which focuses on one disciplinary field, requires modification in the consideration of a biodefense ethic to include not one discipline, but many. The consideration of an ethic in biodefense must capture issues in a multidisciplinary scope, including the ethical studies in the disciplines of medicine, sciences, technology, law, international relations, public health, environment, and war, each having their unique framework of ethical constructs.An ethic of bioterrorism and biodefense raises issues which can be examined utilizing multidisciplinary ethical considerations. The disciplines of medicine, sciences, technology, law, international relations, public health, environment, and war each have a framework of ethical principles which are essential in the scope of ethics which are incident to bioterrorism and biodefense; the absence of any one of which would create a void in our understanding of the complexity of this subject.

An introduction to Volume 3 of the Journal for Biosecurity, Biosafety and Biodefense Law which raises new and important legal issues within the field of biosecurity, biosafety, and biodefense law, both from a practical as well as a theoretical perspective. Articles cover topics including: proposed regulatory changes to the biosafety and biosecurity regulations; jurisdiction during an international biosecurity incident; biocriminology; biosafety and biosecurity concerns at the border; unregulated areas of science and medicine which may present an increased risk for biosecurity threats; national and international responses to recent disease outbreaks; and pandemic preparedness.

The Biological and Toxins Weapons Convention (BTWC), signed in 1972, is the express sense of 162 nations that as a world community, we agree to the end of the use of biological weapons by state parties. However, the increasing numbers of biological, pharmaceutical and public health facilities, coupled with the biotechnology revolution in the latter part of the 20th century, made the development of preventative code of conduct a priority. Biosafety and biosecurity codes of conduct became a topic for consideration by the BTWC in 2005. To develop this new focus, the BTWC conference held a series of expert meetings culminating with the 2011 Review Conference. Codes of conduct encourage a community approach to formulate acceptable, effective, and reasonably related principles in order to achieve its goals. In order to achieve a collective definition of the priorities or impediments for a biosecurity code of conduct among the representatives of the States Parties, a survey was designed. The survey instrument was designed to be answered during one of the days of the regular intersessional Meetings of Experts of the BTWC on August 27, 2009. This article provides a review and assessment of results of this survey.

A nationwide survey of biodefense researchers assesses the effectiveness of the select agent regulations, 42 CFR Sec. 73, which governs the handling, storage and security of listed biological agents and toxins, in achieving their statutory goals of protecting public health and national security. Conducted in 2007 and 2008 among funded biodefense researchers, 509 PIs and Co-PIs were surveyed, with 198 responses (39%).Regulatory components are assessed and an "anxiety factor" is measured indicating high anxiety about inadvertently violating these regulations, leading to negative career impacts, potentially thwarting achieving the goals of the statute.

In the United States a rapidly increasing regulatory burden for life scientists has led to questions of whether the increased burden resulting from the Select Agent Program has had adverse effects on scientific advances. Attention has focussed on the regulatory "fit" of the Program and ways in which its design could be improved. An international framework convention to address common concerns about biosecurity and biosafety is a logical next step.

1. INTRODUCTION The environment and public health goals hold a common value of healthy populations. The threat of bioterrorism requires a partnership of both, building upon the long history of the link between public health and the environment. This existing relationship is key to an effective system of biodefense for the nation, because the use of biological weapons through every environmental pathway poses a potential threat. Contaminations of water, growing crops, grazing cattle, air through inhalation, dermal absorption, or consumption of food or water in the human environment are potential delivery methods. For these risks of bioterrorism in the environment, there is an existing federal regulatory and statutory framework upon which the relationship between the environment and public health can be strengthened and shaped. We took a narrower approach to public health priorities in the environment in 1962 with the publication of Silent Spring,1 which shifted the direct public health effects regulation to a broader environmental protection policy, which took a more comprehensive, holistic approach to human health. This Article examines two important features of change in the post-9-11 relationship between public health, public health law, and environmental law. The first is an immediate change in the expansion of environmental laws to address biodefense activities of surveillance and response through either executive action or congressional amendment.2 The second and most pervasive change is the indication of a shift in federalism in public health law, in a way analogous to the development of federal environmental law in the last half of the twentieth century. This Article begins with an examination of the indications of a shift in federalism in public health, and then turns to the changing role of the U.S. Environmental Protection Agency ("EPA") and the application of existing environmental laws to new problems and controversies in bioterrorism. II. THE SHIFT IN FEDERALISM AS A COURSE TOWARD AN EFFECTIVE BIODEFENSE Because modern federal environmental law has a well-established existing regulatory structure, shaped by more than three decades of experience, this framework can present major contributions to a national homeland defense built around federal environmental law expanding on the original effort to protect public health. A. SHIFTING FEDERALISM AND ENVIRONMENTAL LAW The role today of the federal government in environmental protection is the product of the shift from state power over property law and water law,3 to federal power because of the substantial effect on interstate commerce from environmental pollution control and remediation, which has preempted these areas for state control. An example of this shift in federalism can be observed in the area of regulation of water pollution. The first action by Congress involving the effects of dumping trash and materials into rivers was through the regulation of "navigable waters" in the U.S. Rivers and Harbors Act of 1899(4) and the Refuse Act of 1899.5 The primary purpose was to protect the rivers for navigation and to avoid impeding navigation traffic with trash or lumber and wood floating in the rivers obstructing shipping.6 The Water Pollution Control Act of 1948(7) was the first comprehensive act to address the growing concern for water pollution but did little more than underscore states' responsibilities for water. This Act was replaced by the Water Pollution Control Act Amendments of 1956(8) which were intended to "extend and strengthen" the 1948 Act, and emphasized the continuing responsibilities of the state in controlling water pollution.9 The House Report from the Committee on Public Works stated that: The bill as reported reemphasizes the policy of the Congress to recognize, preserve, and protect the primary rights and responsibilities of the States in controlling water pollution . . . . Regulatory authority at the Federal level should be limited to interstate pollution problems and used on a standby basis only for serious situations and which are not resolved through State and interstate collaboration. …

The US approach to defense against bioterrorism is necessarily constrained by existing legal frameworks. Biodefense research also responds to the development of new laws designed to address bioterrorism threats, but for the most part, technology is not driving the development of new law. While the biotechnology revolution has resulted in a wide range of biodefense applications, these can be used only within existing constitutional restraints and statutory frameworks. These rules, including safety precautions, privacy concerns, and compensatory systems, will continue to shape technologies to fit within those constraints. Several examples demonstrate that technology cannot be used in ways that threaten the legal foundations of our society. Thus technology is now being challenged to come up with more rule-sensitive approaches. In other areas, such as research priorities, progress toward an effective biodefense would be better served by prioritizing research according to scientifically based organizing principles. In order to reach the next level of effectiveness in biodefense, we must understand the complex interrelations of biotechnology and law.