Swine influenza A virus: challenges and novel vaccine strategies

Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control

What Do Nectaris Basin Impact Melt Rocks Look like and Where Can We Find Them?

The formation of the Nectaris basin is a key event defining the stratigraphy of the Moon. Its absolute age, therefore, is a linchpin for lunar bombardment history. Fernandes et al. gave a thorough account of the history of different samples thought to originate in Nectaris, with the upshot being there is little agreement on what samples represent Nectaris, if any. We are revisiting the effort to identify Nectaris basin impact-melt rocks at the Apollo 16 site, to model their emplacement, and to use these parameters to examine other sites where Nectaris impact melt is more abundant and/or more recognizable for potential further study

Nontarget emotional stimuli must be highly conspicuous to modulate the attentional blink

The attentional blink (AB) is often considered a top-down phenomenon because it is triggered by matching an initial target (T1) in a rapid serial visual presentation (RSVP) stream to a search template. However, the AB is modulated when targets are emotional, and is evoked when a task-irrelevant, emotional critical distractor (CDI) replaces T1. Neither manipulation fully captures the interplay between bottom-up and top-down attention in the AB: Valenced targets intrinsically conflate top-down and bottom-up attention. The CDI approach cannotmanipulate second target (T2) valence, which is critical because valenced T2s can “break through” the AB (in the target-manipulation approach). The present research resolves this methodological challenge by indirectly measuring whether a purely bottom-up CDI can modulate report of a subsequent T2. This novel approach adds a valenced CDI to the “classic,” two-target AB. Participants viewed RSVP streams containing a T1–CDI pair preceding a variable lag to T2. If the CDI’s valence is sufficient to survive the AB, it should modulate T2 performance, indirectly signaling bottom-up capture by an emotional stimulus. Contrary to this prediction, CDI valence only affected the AB when CDIs were also extremely visually conspicuous. Thus, emotional valence alone is insufficient to modulate the AB

Record-setting Cosmic-ray Intensities in 2009 and 2010

We report measurements of record-setting intensities of cosmic-ray nuclei from C to Fe, made with the Cosmic Ray Isotope Spectrometer carried on the Advanced Composition Explorer in orbit about the inner Sun-Earth Lagrangian point. In the energy interval from ~70 to ~450 MeV nucleon^(–1), near the peak in the near-Earth cosmic-ray spectrum, the measured intensities of major species from C to Fe were each 20%-26% greater in late 2009 than in the 1997-1998 minimum and previous solar minima of the space age (1957-1997). The elevated intensities reported here and also at neutron monitor energies were undoubtedly due to several unusual aspects of the solar cycle 23/24 minimum, including record-low interplanetary magnetic field (IMF) intensities, an extended period of reduced IMF turbulence, reduced solar-wind dynamic pressure, and extremely low solar activity during an extended solar minimum. The estimated parallel diffusion coefficient for cosmic-ray transport based on measured solar-wind properties was 44% greater in 2009 than in the 1997-1998 solar-minimum period. In addition, the weaker IMF should result in higher cosmic-ray drift velocities. Cosmic-ray intensity variations at 1 AU are found to lag IMF variations by 2-3 solar rotations, indicating that significant solar modulation occurs inside ~20 AU, consistent with earlier galactic cosmic-ray radial-gradient measurements. In 2010, the intensities suddenly decreased to 1997 levels following increases in solar activity and in the inclination of the heliospheric current sheet. We describe the conditions that gave cosmic rays greater access to the inner solar system and discuss some of their implications

Lunar lander conceptual design

This paper is a first look at the problems of building a lunar lander to support a small lunar surface base. A series of trade studies was performed to define the lander. The initial trades concerned choosing number of stages, payload mass, parking orbit altitude, and propellant type. Other important trades and issues included plane change capability, propellant loading and maintenance location, and reusability considerations. Given a rough baseline, the systems were then reviewed. A conceptual design was then produced. The process was carried through only one iteration. Many more iterations are needed. A transportation system using reusable, aerobraked orbital transfer vehicles (OTV's) is assumed. These OTV's are assumed to be based and maintained at a low Earth orbit (LEO) space station, optimized for transportation functions. Single- and two-stage OTV stacks are considered. The OTV's make the translunar injection (TLI), lunar orbit insertion (LOI), and trans-Earth injection (TEI) burns, as well as midcourse and perigee raise maneuvers

Radiation Tolerant, FPGA-Based SmallSat Computer System

The Radiation Tolerant, FPGA-based SmallSat Computer System (RadSat) computing platform exploits a commercial off-the-shelf (COTS) Field Programmable Gate Array (FPGA) with real-time partial reconfiguration to provide increased performance, power efficiency and radiation tolerance at a fraction of the cost of existing radiation hardened computing solutions. This technology is ideal for small spacecraft that require state-of-the-art on-board processing in harsh radiation environments but where using radiation hardened processors is cost prohibitive

Expanding Mouse-Adapted Yamagata-like Influenza B Viruses in Eggs Enhances In Vivo Lethality in BALB/c Mice

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells (London line) for use in challenge studies. We observed that virus grown in embryonated eggs was significantly more lethal in mice than the same virus grown in cell culture. Ten additional serial lung passages of one strain again showed virus grown in eggs was more lethal than virus grown in cells. Additionally, no mutations in the surface glycoprotein amino acid sequences correlated to differences in lethality. Our results suggest growth system can influence lethality of mouse-adapted IBVs after serial lung passaging. Further research can highlight improved mechanisms for developing animal disease models for IBV vaccine research

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the utility of serotype-switching to enhance the protective immune responses seen with homologous prime-boosting strategies. Immunization with an H2 centralized consensus showed a wide breadth of antibody responses after vaccination, protection against challenge with a divergent human H2 strain, and significantly reduced viral load in the lungs after challenge. Further, serotype switching between two species C adenoviruses enhanced protective antibody titers after heterologous boosting. These data support the notion that an adenoviral-vectored H2 centralized consensus vaccine has the ability to provide broadly cross-reactive immune responses to protect against divergent strains of H2 influenza and prepare for a possible pandemic

Does the worsening galactic cosmic radiation environment observed by CRaTER preclude future manned deep space exploration?

Abstract The Sun and its solar wind are currently exhibiting extremely low densities and magnetic field strengths, representing states that have never been observed during the space age. The highly abnormal solar activity between cycles 23 and 24 has caused the longest solar minimum in over 80 years and continues into the unusually small solar maximum of cycle 24. As a result of the remarkably weak solar activity, we have also observed the highest fluxes of galactic cosmic rays in the space age and relatively small solar energetic particle events. We use observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter to examine the implications of these highly unusual solar conditions for human space exploration. We show that while these conditions are not a show stopper for long-duration missions (e.g., to the Moon, an asteroid, or Mars), galactic cosmic ray radiation remains a significant and worsening factor that limits mission durations. While solar energetic particle events in cycle 24 present some hazard, the accumulated doses for astronauts behind 10 g/cm2 shielding are well below current dose limits. Galactic cosmic radiation presents a more significant challenge: the time to 3% risk of exposure-induced death (REID) in interplanetary space was less than 400 days for a 30 year old male and less than 300 days for a 30 year old female in the last cycle 23–24 minimum. The time to 3% REID is estimated to be ∼20% lower in the coming cycle 24–25 minimum. If the heliospheric magnetic field continues to weaken over time, as is likely, then allowable mission durations will decrease correspondingly. Thus, we estimate exposures in extreme solar minimum conditions and the corresponding effects on allowable durations

Multivalent Epigraph Hemagglutinin Vaccine Protects against Influenza B Virus in Mice

Influenza B virus is a respiratory pathogen that contributes to seasonal epidemics, accounts for approximately 25% of global influenza infections, and can induce severe disease in young children. While vaccination is the most commonly used method of preventing influenza infections, current vaccines only induce strain-specific responses and have suboptimal efficacy when mismatched from circulating strains. Further, two influenza B virus lineages have been described, B/Yamagatalike and B/Victoria-like, and the limited cross-reactivity between the two lineages provides an additional barrier in developing a universal influenza B virus vaccine. Here, we report a novel multivalent vaccine using computationally designed Epigraph hemagglutinin proteins targeting both the B/Yamagata-like and B/Victoria-like lineages. When compared to the quadrivalent commercial vaccine, the Epigraph vaccine demonstrated increased breadth of neutralizing antibody and T cell responses. After lethal heterologous influenza B virus challenge, mice immunized with the Epigraph vaccine were completely protected against both weight loss and mortality. The superior cross-reactive immunity conferred by the Epigraph vaccine immunogens supports their continued investigation as a universal influenza B virus vaccine