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Background Studies have reported that repeated annual vaccination may influence influenza vaccination effectiveness in the current season. Methods We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok; Sanofi Pasteur) in adults 18–45 years of age. In the first 2 years, participants were randomized to receive vaccine or saline placebo as follows: placebo-placebo (P-P), placebo-vaccine (P-V), or vaccine-vaccine (V-V). Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of serum samples collected at 5 time points from 95 participants were tested for antibodies against vaccine strains. Results From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with smaller increases for repeat vaccinees who on average had higher prevaccination titers in year 2. There were statistically significant differences in the proportions of participants achieving ≥4-fold rises in antibody titer for the repeat vaccinees for influenza A(H1N1), B/Victoria, and B/Yamagata, but not for A(H3N2). Among participants who received vaccination in year 2, there were no significant differences between the P-V and V-V groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains. Conclusions In the first 2 years, during which influenza did not circulate, repeat and first-time vaccinees had similar postvaccination geometric mean titers to all 4 vaccine strains, indicative of similar levels of clinical protection. Clinical Trials Registration. NCT04576377 [ABSTRACT FROM AUTHOR]

Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life. [ABSTRACT FROM AUTHOR]

Permafrost-affected ecosystems of the Arctic–boreal zone in northwestern North America are undergoing profound transformation due to rapid climate change. NASA's Arctic Boreal Vulnerability Experiment (ABoVE) is investigating characteristics that make these ecosystems vulnerable or resilient to this change. ABoVE employs airborne synthetic aperture radar (SAR) as a powerful tool to characterize tundra, taiga, peatlands, and fens. Here, we present an annotated guide to the L-band and P-band airborne SAR data acquired during the 2017, 2018, 2019, and 2022 ABoVE airborne campaigns. We summarize the ∼80 SAR flight lines and how they fit into the ABoVE experimental design (Miller et al., 2023; https://doi.org/10.3334/ORNLDAAC/2150). The Supplement provides hyperlinks to extensive maps, tables, and every flight plan as well as individual flight lines. We illustrate the interdisciplinary nature of airborne SAR data with examples of preliminary results from ABoVE studies including boreal forest canopy structure from TomoSAR data over Delta Junction, AK, and the Boreal Ecosystem Research and Monitoring Sites (BERMS) area in northern Saskatchewan and active layer thickness and soil moisture data product validation. This paper is presented as a guide to enable interested readers to fully explore the ABoVE L- and P-band airborne SAR data (https://uavsar.jpl.nasa.gov/cgi-bin/data.pl). [ABSTRACT FROM AUTHOR]

mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Venus Evolution Through Time: Key Science Questions, Selected Mission Concepts and Future Investigations." The correction addresses a discrepancy between values mentioned in the text and in Table 1 of the original publication. The corrected version states that the gravity field harmonic coefficients are generated up to an average degree strength of 200, rather than 130 as previously stated. The correction is provided by various authors and the publisher, Springer Nature, remains neutral in regards to jurisdictional claims and institutional affiliations. [Extracted from the article]

In this work we discuss various selected mission concepts addressing Venus evolution through time. More specifically, we address investigations and payload instrument concepts supporting scientific goals and open questions presented in the companion articles of this volume. Also included are their related investigations (observations & modeling) and discussion of which measurements and future data products are needed to better constrain Venus' atmosphere, climate, surface, interior and habitability evolution through time. A new fleet of Venus missions has been selected, and new mission concepts will continue to be considered for future selections. Missions under development include radar-equipped ESA-led EnVision M5 orbiter mission (European Space Agency 2021), NASA-JPL's VERITAS orbiter mission (Smrekar et al. 2022a), NASA-GSFC's DAVINCI entry probe/flyby mission (Garvin et al. 2022a). The data acquired with the VERITAS, DAVINCI, and EnVision from the end of this decade will fundamentally improve our understanding of the planet's long term history, current activity and evolutionary path. We further describe future mission concepts and measurements beyond the current framework of selected missions, as well as the synergies between these mission concepts, ground-based and space-based observatories and facilities, laboratory measurements, and future algorithmic or modeling activities that pave the way for the development of a Venus program that extends into the 2040s (Wilson et al. 2022). [ABSTRACT FROM AUTHOR]

Permafrost-affected ecosystems of the Arctic-boreal zone in northwestern North America are undergoing profound transformation due to rapid climate change. NASA's Arctic Boreal Vulnerability Experiment (ABoVE) is investigating characteristics that make these ecosystems vulnerable or resilient to this change. ABoVE employs airborne synthetic aperture radar (SAR) as a powerful tool to characterize tundra, taiga, peatlands, and fens. Here, we present an annotated guide to the L-band and P band airborne SAR data acquired during the 2017, 2018, 2019, and 2022 ABoVE airborne campaigns. We summarize the ~80 SAR flight lines and how they fit into the ABoVE experimental design. We provide hyperlinks to extensive maps, tables, and every flight plan as well as individual flight lines. We illustrate the interdisciplinary nature of airborne SAR data with examples of preliminary results from ABoVE studies including: boreal forest canopy structure from tomoSAR data over Delta Junction, AK and the BERMS site in northern Saskatchewan and active layer thickness and soil moisture data product validation. This paper is presented as a guide to enable interested readers to fully explore the ABoVE L55 and P-band SAR data. [ABSTRACT FROM AUTHOR]

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus--specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS- CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine- tuning effector functionality but also for binding and neutralization of antigenically drifted viruses. [ABSTRACT FROM AUTHOR]

Photogeologic principles can be used to suggest possible sequences of events that result in the present planetary surface. The most common method of evaluating the absolute age of a planetary surface remotely is to count the number of impact craters that have occurred after the surface formed, with the assumption that the craters occur in a spatially random fashion over time. Using additional assumptions, craters that have been partially modified by later geologic activity can be used to assess the time frames for an interpreted sequence of events. The total number of craters on Venus is low and the spatial distribution taken by itself is nearly indistinguishable from random. The overall implication is that the Venusian surface is much closer to Earth in its youthfulness than the other, smaller inner solar system bodies. There are differing interpretations of the extent to which volcanism and tectonics have modified the craters and of the regional and global sequences of geologic events. Consequently, a spectrum of global resurfacing views has emerged. These range from a planet that has evolved to have limited current volcanism and tectonics concentrated in a few zones to a planet with Earth-like levels of activity occurring everywhere at similar rates but in different ways. Analyses of the geologic record have provided observations that are challenging to reconcile with either of the endmember views. The interpretation of a global evolution with time in the nature of geologic activity relies on assumptions that have been challenged, but there are other observations of areally extensive short-lived features such as canali that are challenging to reconcile with a view of different regions evolving independently. Future data, especially high-resolution imaging and topography, can provide the details to resolve some of the issues. These different global-evolution viewpoints must tie to assessments of present-day volcanic and tectonic activity levels that can be made with the data from upcoming missions. [ABSTRACT FROM AUTHOR]

This paper proposes an improved model-based forest height inversion method for airborne L-band dual-baseline repeat-pass polarimetric synthetic aperture radar interferometry (PolInSAR) collections. A two-layer physical model with various volumetric scattering attenuation and dynamic motion properties is first designed based on the traditional Random Motion over Ground (RMoG) model. Related PolInSAR coherence functions with both volumetric and temporal decorrelations incorporated are derived, where the impacts of homogenous and heterogeneous attenuation and dynamic motion properties on the performance of forest height inversion were investigated by the Linear Volume Attenuation (LVA), Quadratic Volume Attenuation (QVA), Linear Volume Motion (LVM), and Quadratic Volume Motion (QVM) depictions in the volume layer. Dual-baseline PolInSAR data were acquired to increase the degree of freedom (DOF) of the coherence observations and thereby provide extra constraints on the forest parameters to address the underdetermined problem. The experiments were carried out on a boreal forest in Canada and a tropical one in Gabon, where physical models with LVA + QVM (RMSE: 3.56 m) and QVA + LVM (RMSE: 6.83 m) exhibited better performances on the forest height inversion over the boreal and tropical forest sites, respectively. To leverage the advantages of LVA, QVA, LVM, and QVM, a pixel-wise optimization strategy was used to obtain the best forest height inversion performance for the range of attenuation and motion profiles considered. This pixel-wise optimization surpasses the best-performing single model and achieves forest height inversion results with an RMSE of 3.21 m in the boreal forest site and an RMSE of 6.48 m in the tropical forest site. [ABSTRACT FROM AUTHOR]

Some risk factors for severe coronavirus disease 2019 (COVID-19) have been identified, including age, race, and obesity. However, 20%-50% of severe cases occur in the absence of these factors. Cytomegalovirus (CMV) is a herpesvirus that infects about 50% of all individuals worldwide and is among the most significant nongenetic determinants of immune system. We hypothesized that latent CMV infection might influence the severity of COVID-19. Our analyses demonstrate that CMV seropositivity is associated with more than twice the risk of hospitalization due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune profiling of blood and CMV DNA quantitative polymerase chain reaction in a subset of patients for whom respiratory tract samples were available revealed altered T-cell activation profiles in absence of extensive CMV replication in the upper respiratory tract. These data suggest a potential role for CMV-driven immune perturbations in affecting the outcome of SARS-CoV-2 infection and may have implications for the discrepancies in COVID-19 severity between different human populations. [ABSTRACT FROM AUTHOR]

Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2-specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has given rise to the devastating global pandemic. In most cases, SARS-CoV-2 infection results in the development of viral pneumonia and acute respiratory distress syndrome, known as 'coronavirus disease 2019' or COVID-19. Intriguingly, besides the respiratory tract, COVID-19 affects other organs and systems of the human body. COVID-19 patients with pre-existing cardiovascular disease have a higher risk of death, and SARS-CoV-2 infection itself may cause myocardial inflammation and injury. One possible explanation of such phenomena is the fact that SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the receptor required for viral entry. ACE2 is expressed in the cells of many organs, including the heart. ACE2 functions as a carboxypeptidase that can cleave several endogenous substrates, including angiotensin II, thus regulating blood pressure and vascular tone. It remains largely unknown if the SARS-CoV-2 infection alters the enzymatic properties of ACE2, thereby contributing to cardiovascular complications in patients with COVID-19. Here, we demonstrate that ACE2 cleavage of des-Arg9-bradykinin substrate analogue is markedly accelerated, while cleavage of angiotensin II analogue is minimally affected by the binding of spike protein. These findings may have implications for a better understanding of COVID-19 pathogenesis. [ABSTRACT FROM AUTHOR]

Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne infection is still unknown. Using the ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We demonstrate that a 48 hour exposure is sufficient for efficient transmission of H1N1 and H3N2 viruses. To test pre-existing immunity, a gap of 8–12 weeks between primary and secondary infections was imposed to reduce innate responses and ensure robust infection of donor animals with heterosubtypic viruses. We found that pre-existing H3N2 immunity did not significantly block transmission of the 2009 H1N1pandemic (H1N1pdm09) virus to immune animals. Surprisingly, airborne transmission of seasonal H3N2 influenza strains was abrogated in recipient animals with H1N1pdm09 pre-existing immunity. This protection from natural infection with H3N2 virus was independent of neutralizing antibodies. Pre-existing immunity with influenza B virus did not block H3N2 virus transmission, indicating that the protection was likely driven by the adaptive immune response. We demonstrate that pre-existing immunity can impact susceptibility to heterologous influenza virus strains, and implicate a novel correlate of protection that can limit the spread of respiratory pathogens through the air. Author summary: Influenza viruses pose a major public health threat through both seasonal epidemics and sporadic pandemics. An individual's first influenza virus infection leaves long-lasting immunity, which plays an unknown role on susceptibility to airborne transmission of new viral strains. We show that pre-existing heterosubtypic immunity against the 2009 H1N1 pandemic virus protects recipient animals from airborne transmission of a seasonal H3N2 influenza virus, which is independent of cross-neutralizing antibodies. Pre-existing immunity with influenza B viruses was not protective suggesting that this phenomenon is driven by an adaptive response. Taken together, these data indicate that pre-existing immunity is an important barrier to airborne transmission and can influence the emergence and spread of potentially pandemic viruses. [ABSTRACT FROM AUTHOR]

Background The H3N2 component of egg-based 2017–2018 influenza vaccines possessed an adaptive substitution that alters antigenicity. Several influenza vaccines include antigens that are produced through alternative systems, but a systematic comparison of different vaccines used during the 2017–2018 season has not been completed. Methods We compared antibody responses in humans vaccinated with Fluzone (egg-based, n = 23), Fluzone High-Dose (egg-based, n = 16), Flublok (recombinant protein–based, n = 23), or Flucelvax (cell-based, n = 23) during the 2017–2018 season. We completed neutralization assays using an egg-adapted H3N2 virus, a cell-based H3N2 virus, wild-type 3c2.A and 3c2.A2 H3N2 viruses, and the H1N1 vaccine strain. We also performed enzyme-linked immunosorbent assays using a recombinant wild-type 3c2.A hemagglutinin. Antibody responses were compared in adjusted analysis. Results Postvaccination neutralizing antibody titers to 3c2.A and 3c2.A2 were higher in Flublok recipients compared with Flucelvax or Fluzone recipients (P <.01). Postvaccination titers to 3c2.A and 3c2.A2 were similar in Flublok and Fluzone High-Dose recipients, though seroconversion rates trended higher in Flublok recipients. Postvaccination titers in Flucelvax recipients were low to all H3N2 viruses tested, including the cell-based H3N2 strain. Postvaccination neutralizing antibody titers to H1N1 were similar among the different vaccine groups. Conclusions These data suggest that influenza vaccine antigen match and dose are both important for eliciting optimal H3N2 antibody responses in humans. Future studies should be designed to determine if our findings directly impact vaccine effectiveness. Clinical Trials Registration NCT03068949. [ABSTRACT FROM AUTHOR]

Immunity to influenza viruses can be long-lived, but reinfections with antigenically distinct viral strains and subtypes are common. Reinfections can boost antibody responses against viral strains first encountered in childhood through a process termed "original antigenic sin." It is unknown how initial childhood exposures affect the induction of antibodies against the hemagglutinin (HA) stalk domain of influenza viruses. This is an important consideration since broadly reactive HA stalk antibodies can protect against infection, and universal vaccine platforms are being developed to induce these antibodies. Here we show that experimentally infected ferrets and naturally infected humans establish strong "immunological imprints" against HA stalk antigens first encountered during primary influenza virus infections. We found that HA stalk antibodies are surprisingly boosted upon subsequent infections with antigenically distinct influenza A virus subtypes. Paradoxically, these heterosubtypic-boosted HA stalk antibodies do not bind efficiently to the boosting influenza virus strain. Our results demonstrate that an individual's HA stalk antibody response is dependent on the specific subtype of influenza virus that they first encounter early in life. We propose that humans are susceptible to heterosubtypic influenza virus infections later in life since these viruses boost HA stalk antibodies that do not bind efficiently to the boosting antigen. [ABSTRACT FROM AUTHOR]

The 2019–2020 Northern Hemisphere influenza vaccine includes antigens from 3c3.A H3N2 viruses; however, over half of circulating H3N2 viruses belong to subclade 3c2.A1b. Here, we analyze antibody responses elicited by the egg-adapted 3c3.A H3N2 vaccine strain in ferrets and humans. We find that this vaccine strain elicits antibodies that have reduced reactivity to a wild-type 3c3.A strain and very limited reactivity to 3c2.A strains, including the currently circulating 3c2.A1b strain. Vaccine mismatch and changes in antigenicity due to vaccine strain egg adaptation can affect seasonal influenza vaccine effectiveness. Here, Gouma et al. show that the egg-adapted 3c3.A H3N2 vaccine strain elicits antibodies with limited reactivity to a wildtype 3c3.A strain and currently circulating 3c2.A H3N2 strains. [ABSTRACT FROM AUTHOR]

Do mother's antibodies know best?: Infants are susceptible to many infections. One promising strategy to shield them is through vaccination of mothers during pregnancy, thus providing maternal antibodies that can temporarily protect infants from disease. However, maternal antibodies can also prevent infants from developing their own antibody responses that are necessary for long-term protection. Willis et al. now show that an influenza vaccine consisting of nucleoside-modified mRNAs encapsulated in lipid nanoparticles elicited protective antibodies in mouse pups in the presence of maternal antibodies. These authors show that, unlike conventional influenza vaccines, the mRNA vaccine is able to partially overcome the inhibitory effects of maternal antibodies in mouse pups. Maternal antibodies provide short-term protection to infants against many infections. However, they can inhibit de novo antibody responses in infants elicited by infections or vaccination, leading to increased long-term susceptibility to infectious diseases. Thus, there is a need to develop vaccines that are able to elicit protective immune responses in the presence of antigen-specific maternal antibodies. Here, we used a mouse model to demonstrate that influenza virus–specific maternal antibodies inhibited de novo antibody responses in mouse pups elicited by influenza virus infection or administration of conventional influenza vaccines. We found that a recently developed influenza vaccine, nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP), partially overcame this inhibition by maternal antibodies. The mRNA-LNP influenza vaccine established long-lived germinal centers in the mouse pups and elicited stronger antibody responses than did a conventional influenza vaccine approved for use in humans. Vaccination with mRNA-LNP vaccines may offer a promising strategy for generating robust immune responses in infants in the presence of maternal antibodies. [ABSTRACT FROM AUTHOR]

Interferogram filtering for noise reduction is a key to many radar interferometric applications. Repeat pass radar interferometry often uses data with less than ideal correlation levels resulting from either long spatial or temporal baselines or changes between observations leading to high levels of temporal correlation. To maximize the utility of such pairs filtering the interferogram to get maximal noise reduction is often needed. One technique that has proved quite useful in the geophysical community is power spectral or Goldstein–Werner filtering of the interferogram whereby a power-weighted version of the Fourier transform is used to enhance fringe visibility. Although this paper defining the filter briefly touched upon the spatial resolution and noise reduction induced by the filter, it did not provide a useful formula for predicting the phase noise after filtering. This paper derives a formula for the phase noise obtained from power spectral filtering albeit under the restriction of several simplifying assumptions to make the problem analytically tractable. In particular, it is assumed that the interferometric phase is locally well approximated by a linear phase ramp with nonlinear phase perturbations small in a spectral energy sense compared to the linear term. [ABSTRACT FROM AUTHOR]

Influenza viruses routinely acquire mutations in their hemagglutinin (HA) and neuraminidase (NA) glycoproteins that abrogate binding of pre-existing antibodies in a process known as antigenic drift. Most human antibodies against HA and NA are directed against epitopes that are hypervariable and not against epitopes that are conserved among different influenza virus strains. Universal influenza vaccines are currently being developed to elicit protective responses against functionally conserved sites on influenza proteins where viral escape mutations can result in large fitness costs [1]. Universal vaccine targets include the highly conserved HA stem domain [2-12], the less conserved HA receptor-binding site (RBS) [13-16], as well as conserved sites on NA [17-19]. One central challenge of universal vaccine efforts is to steer human antibody responses away from immunodominant, variable epitopes and towards subdominant, functionally conserved sites. Overcoming this challenge will require further understanding of the structural basis of broadly neutralizing HA and NA antibody binding epitopes and factors that influence immunodominance hierarchies of human antibody responses. [ABSTRACT FROM AUTHOR]

Here, we find that the egg-adapted H3N2 component of the 2019 Southern Hemisphere influenza vaccine elicits an antibody response in ferrets that is highly focused on antigenic site A of hemagglutinin. This is potentially problematic as most H3N2 viruses currently circulating in the Southern Hemisphere possess antigenic site A substitutions. [ABSTRACT FROM AUTHOR]

Subsurface imaging in arid regions is a well-known application of satellite Synthetic Aperture Radar (SAR). Archaeological prospection has often focused on L-band SAR sensors, given the ability of longer wavelengths to penetrate more deeply into sand. In contrast, this study demonstrates capabilities of shorter-wavelength, but higher spatial resolution, C-band and X-band SAR sensors in archaeological subsurface imaging at the site of 'Uqdat al-Bakrah (Safah), Oman. Despite having varying parameters and acquisitions, both the X-band and C-band images analyzed were able to identify a subsurface paleo-channel that is not visible on the ground surface. This feature was first identified through Ground Penetrating Radar (GPR) survey, then recognized in the SAR imagery and further verified by test excavations. Both the GPR and the excavations reveal the base of the paleo-channel at a depth of 0.6 m-0.7 m. Hence, both X-band and C-band wavelengths are appropriate for subsurface archaeological prospection in suitable (dry silt and sand) conditions with specific acquisition parameters. Moreover, these results offer important new insights into the paleo-environmental context of ancient metal-working at 'Uqdat al-Bakrah and demonstrate surface water flow roughly contemporary with the site's occupation. [ABSTRACT FROM AUTHOR]

Currently available influenza virus vaccines have inadequate effectiveness and are reformulated annually due to viral antigenic drift. Thus, development of a vaccine that confers long-term protective immunity against antigenically distant influenza virus strains is urgently needed. The highly conserved influenza virus hemagglutinin (HA) stalk represents one of the potential targets of broadly protective/universal influenza virus vaccines. Here, we evaluate a potent broadly protective influenza virus vaccine candidate that uses nucleoside-modified and purified mRNA encoding full-length influenza virus HA formulated in lipid nanoparticles (LNPs). We demonstrate that immunization with HA mRNA-LNPs induces antibody responses against the HA stalk domain of influenza virus in mice, rabbits, and ferrets. The HA stalk-specific antibody response is associated with protection from homologous, heterologous, and heterosubtypic influenza virus infection in mice. [ABSTRACT FROM AUTHOR]

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. [ABSTRACT FROM AUTHOR]

H3N2 viruses continuously acquire mutations in the hemagglutinin (HA) glycoprotein that abrogate binding of human antibodies. During the 2014-2015 influenza season, clade 3C.2a H3N2 viruses possessing a new predicted glycosylation site in antigenic site B of HA emerged, and these viruses remain prevalent today. The 2016-2017 seasonal influenza vaccine was updated to include a clade 3C.2a H3N2 strain; however, the egg-adapted version of this viral strain lacks the new putative glycosylation site. Here, we biochemically demonstrate that the HA antigenic site B of circulating clade 3C.2a viruses is glycosylated. We show that antibodies elicited in ferrets and humans exposed to the egg-adapted 2016-2017 H3N2 vaccine strain poorly neutralize a glycosylated clade 3C.2a H3N2 virus. Importantly, antibodies elicited in ferrets infected with the current circulating H3N2 viral strain (that possesses the glycosylation site) and humans vaccinated with baculovirus-expressed H3 antigens (that possess the glycosylation site motif) were able to efficiently recognize a glycosylated clade 3C.2a H3N2 virus. We propose that differences in glycosylation between H3N2 egg-adapted vaccines and circulating strains likely contributed to reduced vaccine effectiveness during the 2016-2017 influenza season. Furthermore, our data suggest that influenza virus antigens prepared via systems not reliant on egg adaptations are more likely to elicit protective antibody responses that are not affected by glycosylation of antigenic site B of H3N2 HA. [ABSTRACT FROM AUTHOR]

Surface cross-track clutter can corrupt both earth and planetary radar sounder (RS) observations preventing definitive interpretation of subsurface features, which are often of primary interest to geologists and planetary scientists. This clutter is usually identified either by manual or automatic techniques that require ancillary information about the topography of the surface, or by using multichannel RS systems with arrays of antennas. However, topographic information is not always available and multichannel systems are generally too massive and costly to mount on satellites for the planetary exploration. In this paper, we propose a novel approach to clutter discrimination that is independent of ancillary information and limits the hardware complexity of the RS system. This approach uses a two-channel RS and exploits cross-channel interferometric phase differences to discriminate the clutter. Our approach includes three main steps: 1) manual feature extraction and theoretical phase-difference estimation; 2) RS interferogram formation; and 3) comparison of theoretical and real phase difference distributions. The proposed method was validated on RS data acquired in Greenland and provides a proof of concept for the surface clutter discrimination using RS data. [ABSTRACT FROM PUBLISHER]

The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA) often arise during virus passaging that change its antigenicity and hence vaccine effectiveness. Here, we structurally characterize the effect of a prevalent substitution, L194P, in egg-passaged H3N2 viruses. X-ray structural analysis reveals that this substitution surprisingly increases the mobility of the 190-helix and neighboring regions in antigenic site B, which forms one side of the receptor binding site (RBS) and is immunodominant in recent human H3N2 viruses. Importantly, the L194P substitution decreases binding and neutralization by an RBS-targeted broadly neutralizing antibody by three orders of magnitude and significantly changes the HA antigenicity as measured by binding of human serum antibodies. The receptor binding mode and specificity are also altered to adapt to avian receptors during egg passaging. Overall, these findings help explain the low effectiveness of the seasonal vaccine against H3N2 viruses, and suggest that alternative approaches should be accelerated for producing influenza vaccines as well as isolating clinical isolates. [ABSTRACT FROM AUTHOR]

Differential interferometric synthetic aperture radar (DInSAR) measurements are sensitive to displacements, but also to soil moisture mv changes. Here, we analyze whether soil moisture can be estimated from three DInSAR observables without making any assumptions about its complex spatio-temporal dynamics, with the goal of removing its contribution from the displacement estimates. We find that the referenced DInSAR phase can be a suitable means to estimate mv time series up to an overall offset, as indicated by correlations with in situ measurements of 0.75–0.90 in two campaigns. However, the phase can only be referenced when no displacements (and atmospheric delays) occur or when they can be estimated reliably. We study the separability of displacements and mv using two additional DInSAR observables (closure phase and coherence magnitude) that are sensitive to mv but insensitive to displacements. However, our analyses show that neither contains enough information for this purpose, i.e., it is not possible to estimate mv uniquely. The soil moisture correction of the displacement estimates is hence ambiguous too. Their applicability is furthermore limited by their proneness to model misspecifications and decorrelation. Consequently, the separation of soil moisture changes and displacements using DInSAR observations alone is difficult in practice, and—like for mitigating tropospheric errors—additional data (e.g., external mv estimates) or assumptions (e.g., spatio-temporal patterns) are required when the mv effects on the displacement estimates are comparable to the magnitude of the movements. This will be critical when soil moisture changes are correlated with the actual displacements. [ABSTRACT FROM PUBLISHER]

This letter presents the first demonstration of millimeter-wave single-pass interferometric synthetic aperture radar (InSAR) for snow-depth mapping. Maps are presented over the Tuolumne River Basin region of the Sierra Nevada, CA, USA, and compared with those collected by a scanning lidar onboard the NASA Airborne Snow Observatory for the same region on the same snow day. For this observation, the snow surface was wet and melting and as such penetration of the electromagnetic wave into the snow volume can be effectively neglected. Despite the rugged terrain, heavy tree-cover, and very low snow-volume, depth maps had a standard deviation <1 m with the largest differences occurring on slopes exceeding 40°. While additional evaluation is needed with demonstration of the InSAR capability over a greater range of conditions and terrain, these results are promising. InSAR for snow-depth mapping holds significant advantages for a spaceborne mission if proven viable as it can operate through cloud cover, day or night, and measure snowpack when wet or melting. [ABSTRACT FROM PUBLISHER]

Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation. [ABSTRACT FROM AUTHOR]

T follicular helper (TFH) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTFH, have similarity to lymphoid TFH, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTFH respond in an antigen-specific manner and whether they form long-lasting memory. We identified a cTFH population that expressed multiple T cell activation markers and could be readily identified by coexpression of inducible costimulator (ICOS) and CD38. This subset expressed more Bcl6, c-Maf, and interleukin-21 than did other blood CD4 subsets. Influenza vaccination induced a strong response in the ICOS+CD38+ cTFH at day 7, and this population included hemagglutinin-specific cells by tetramer staining and antigen-stimulated activation-induced marker expression. Moreover, T cell receptor β chain sequencing identified a clonal response in ICOS+CD38+ cTFH that strongly correlated with the increased cTFH frequency and was associated with the circulating plasmablast response. In participants who received successive annual vaccinations, a recurrent oligoclonal response was identified in the ICOS+CD38+ cTFH subset at 7 days after every vaccination. These oligoclonal responses in ICOS+CD38+ cTFH after vaccination persisted in the ICOS−CD38− cTFH repertoire in subsequent years, suggesting clonal maintenance in a memory reservoir in the more stable ICOS−CD38− cTFH subset. These data highlight the antigen specificity, lineage relationships, and memory properties of human cTFH responses to vaccination, providing new avenues for tracking and monitoring cTFH responses during infection and vaccination in humans. [ABSTRACT FROM AUTHOR]

During the 2013-2014 influenza season, nearly all circulating 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) strains possessed an antigenically important mutation in hemagglutinin (K166Q). Here, we performed hemagglutination-inhibition (HAI) assays, using sera collected from 382 individuals prior to the 2013-2014 season, and we determined whether HAI titers were associated with protection from A(H1N1)pdm09 infection. Protection was associated with HAI titers against an A(H1N1)pdm09 strain possessing the K166Q mutation but not with HAI titers against the current A(H1N1)pdm09 vaccine strain, which lacks this mutation. These data indicate that contemporary A(H1N1)pdm09 strains are antigenically distinct from the current A(H1N1)pdm09 vaccine strain. [ABSTRACT FROM AUTHOR]