Description: One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head-based strategy that elicits antibodies against many H1 strains that have undergone genetic drift and has potential as a "subtype universal" vaccine. Nine HA COBRA candidates were developed, and these vaccines were used alone, in cocktails or in prime-boost combinations. The most effective regimens elicited the broadest hemagglutination inhibition (HAI) response against a panel of H1N1 viruses isolated over the past 100 years. This is the first report describing a COBRA-based HA vaccine strategy that elicits a broadly reactive response against seasonal and pandemic H1N1 isolates.

Description: We assess the impact of transport of pollution from midlatitudes on the abundance of ozone in the Arctic in summer 2006 using the GEOS-Chem global chemical transport model and its adjoint. We find that although the impact of midlatitude emissions on ozone abundances in the Arctic is at a maximum in fall and winter, in July transport from North America, Asia, and Europe together contributed about 25% of surface ozone abundances in the Arctic. Throughout the summer, the dominant source of ozone in the Arctic troposphere was photochemical production within the Arctic, which accounted for more than 50% of the ozone in the Arctic boundary layer and as much as 30%–40% of the ozone in the middle troposphere. An adjoint sensitivity analysis of the impact of NOx emissions on ozone at Alert shows that on synoptic time scales in both the lower and middle troposphere, ozone abundances are more sensitive to emissions between 50°N and 70°N, with important influences from anthropogenic, biomass burning, soil, and lightning sources. Although local surface NOx emissions contribute to ozone formation, transport of NOx in the form of peroxyacetyl nitrate (PAN) from outside the Arctic and from the upper troposphere also contributed to ozone production in the lower troposphere. We find that in late May and June the release of NOx from PAN decomposition accounted for 93% and 55% of ozone production at the Arctic surface, respectively.