Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

HAWC Study of Very-High-Energy γ\gamma-ray Spectrum of HAWC J1844-034

Recently, the region surrounding eHWC J1842-035 has been studied extensively by gamma-ray observatories due to its extended emission reaching up to a few hundred TeV and potential as a hadronic accelerator. In this work, we use 1,910 days of cumulative data from the High Altitude Water Cherenkov (HAWC) observatory to carry out a dedicated systematic source search of the eHWC J1842-035 region. During the search we have found three sources in the region, namely, HAWC J1844-034, HAWC J1843-032, and HAWC J1846-025. We have identified HAWC J1844-034 as the extended source that emits photons with energies up to 175 TeV. We compute the spectrum for HAWC J1844-034 and by comparing with the observational results from other experiments, we have identified HESS J1843-033, LHAASO J1843-0338, and TASG J1844-038 as very-high-energy gamma-ray sources with a matching origin. Also, we present and use the multi-wavelength data to fit the hadronic and leptonic particle spectra. We have identified four pulsar candidates in the nearby region from which PSR J1844-0346 is found to be the most likely candidate due to its proximity to HAWC J1844-034 and the computed energy budget. We have also found SNR G28.6-0.1 as a potential counterpart source of HAWC J1844-034 for which both leptonic and hadronic scenarios are feasible.Comment: 13 pages, 9 figures, published in Ap

Validation of standardized data formats and tools for ground-level particle-based gamma-ray observatories

Ground-based gamma-ray astronomy is still a rather young field of research,with strong historical connections to particle physics. This is why mostobservations are conducted by experiments with proprietary data and analysissoftware, as it is usual in the particle physics field. However in recentyears, this paradigm has been slowly shifting towards the development and useof open-source data formats and tools, driven by upcoming observatories such asthe Cherenkov Telescope Array (CTA). In this context, a community-driven,shared data format (the gamma-astro-data-format or GADF) and analysis toolssuch as Gammapy and ctools have been developed. So far these efforts have beenled by the IACT community, leaving out other types of ground-based gamma-rayinstruments.We aim to show that the data from ground particle arrays, such asthe High-Altitude Water Cherenkov (HAWC) observatory, is also compatible withthe GADF and can thus be fully analysed using the related tools, in this caseGammapy. We reproduce several published HAWC results using Gammapy and dataproducts compliant with GADF standard. We also illustrate the capabilities ofthe shared format and tools by producing a joint fit of the Crab spectrumincluding data from six different gamma-ray experiments. We find excellentagreement with the reference results, a powerful check of both the publishedresults and the tools involved. The data from particle detector arrays such asthe HAWC observatory can be adapted to the GADF and thus analysed with Gammapy.A common data format and shared analysis tools allow multi-instrument jointanalysis and effective data sharing. Given the complementary nature of pointingand wide-field instruments, this synergy will be distinctly beneficial for thejoint scientific exploitation of future observatories such as the SouthernWide-field Gamma-ray Observatory and CTA.<br

Simulating the performance of the Southern Wide-view Gamma-ray Observatory

The Southern Wide-view Gamma-ray Observatory (SWGO) will be a next-generation gamma-ray observatory using a large array of particle detectors at a high elevation site in South America. This project is currently in a three years R&amp;D phase in which the design will be optimised for cost and performance. Therefore it is crucial to efficiently evaluate the impact of different design options on the scientific objectives of the observatory. In this contribution, we will introduce the strategy and the simulation framework in which this evaluation takes place

The Southern Wide-field Gamma-ray Observatory reach for Primordial Black Hole evaporation

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Galactic Science with the Southern Wide-field Gamma-ray Observatory

The Southern Wide-field Gamma-ray Observatory (SWGO) is a proposed ground-based gamma-ray detector that will be located in the Southern Hemisphere and is currently in its design phase. In this contribution, we will outline the prospects for Galactic science with this Observatory. Particular focus will be given to the detectability of extended sources, such as gamma-ray halos around pulsars; optimisation of the angular resolution to mitigate source confusion between known TeV sources; and studies of the energy resolution and sensitivity required to study the spectral features of PeVatrons at the highest energies. Such a facility will ideally complement contemporaneous observatories in studies of high energy astrophysical processes in our Galaxy

Monitoring Gamma-Ray Burst VHE emission with the Southern Wide-field-of-view Gamma-ray Observatory

It has been established that Gamma-Ray Bursts (GRB) can produce Very High Energy radiation (E &gt; 100 GeV), opening a new window on the investigation of particle acceleration and radiation properties in the most energetic domain. We expect that next-generation instruments, such as the Cherenkov Telescope Array (CTA), will mark a huge improvement in their observation. However, constraints on the target visibility and the limited duty cycle of Imaging Atmospheric Cherenkov Telescopes (IACT) reduce their ability to react promptly to transient events and to characterise their general properties. Here we show that an instrument based on the Extensive Air Shower (EAS) array concept, proposed by the Southern Wide Field-of-view Gamma-ray Observatory (SWGO) Collaboration, has promising possibilities to detect and track VHE emission from GRBs. Observations made by the Fermi Large Area Telescope (Fermi-LAT) identified some events with a distinct spectral component, extending above 1 GeV or even 10 GeV, which can represent a substantial fraction of the emitted energy and also arise in early stages of the process. Using models based on these properties, we estimate the possibilities that a wide field of view and large effective area ground-based monitoring facility has to probe VHE emission from GRBs. We show that the ability to monitor VHE transients with a nearly continuous scanning of the sky grants an opportunity to access simultaneous electromagnetic counterparts to Multi-Messenger triggers up to cosmological scales, in a way that is not available to IACTs

Benchmarking the Science for the Southern Wide-Field Gamma-ray Observatory (SWGO)

The Southern Wide-field Gamma-ray Observatory (SWGO) is the project to build a new extensive air shower particle detector for the observation of very-high-energy gamma-rays in South America. SWGO is currently planned for installation in the Southern Hemisphere, which grants it a unique science potential among ground-based gamma-ray detectors. It will complement the capabilities of CTA, working as a wide-field instrument for the monitoring of transient and variable phenomena, and will expand the sky coverage of Northern Hemisphere facilities like HAWC and LHAASO, thus granting access to the entire Galactic Plane and the Galactic Center. SWGO aims to achieve excellent sensitivity over a very large target energy range from about 100 GeV to the PeV, and improve on the performance of current sampling array instruments in all observational parameters, including energy and angular resolution, background rejection, and single-muon detection capabilities. The directives for the final observatory design will be given by a number of key science goals which are being defined over the course of the Project’s R&amp;D phase. In this contribution we will present the core science topics and target performance goals that serve as benchmarks to guide SWGO’s design configuration

The TeV Sun Rises: Discovery of Gamma rays from the Quiescent Sun with HAWC

We report the first detection of a TeV gamma-ray flux from the solar disk (6.3$\sigma$), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5--2.6 TeV spectrum is well fit by a power law, dN/dE = $A (E/1 \text{ TeV})^{-\gamma}$, with $A = (1.6 \pm 0.3) \times 10^{-12}$ TeV$^{-1}$ cm$^{-2}$ s$^{-1}$ and $\gamma = -3.62 \pm 0.14$. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.Comment: 15 pages, 8 figures including supplementary material. Accepted for publication in Physical Review Letter

Technological options for the Southern Wide-field Gamma-ray Observatory (SWGO) and current design status

The SWGO Collaboration is in the process of designing and prototyping a wide field of view, high duty cycle complement to CTA and the existing ground-based particle detectors of the Northern Hemisphere (HAWC and LHAASO). In this contribution, we will compare the various technological options for designing the detector and present an overarching system design accommodating them. We will introduce a feasible reference configuration that is used for the first large-scale simulations and cost estimates, and show ongoing prototyping work focused on reaching a maintenance-free and cost-effective detector