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Antibodies against polyethylene glycol (PEG) can critically jeopardize the efficacy and safety of PEGylated therapeutics. For some PEG‐drugs, a sizeable fraction of patients develop anti‐PEG antibodies (APA), leading to reduced efficacy and potential adverse events. We surveyed physicians from several specialties to assess their awareness of APA. Overall, 83% of the physicians surveyed indicated that they have recently prescribed PEGylated drugs. Although 91% of respondents were aware of antidrug antibodies in general, only 22% were aware of APA responses. Further, there was limited awareness (35%) of PEG's inclusion in prescribed PEGylated therapeutics. These findings bring to light a need for improved awareness of APA, potentially via targeted education of physicians who prescribe specific PEGylated therapeutics that could induce or are otherwise affected by APA. Finally, it will be critical to quantitate the extent of knowledge transfer from the research community to clinicians, especially on topics of patient safety.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID‐19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self‐dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc‐mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID‐19 in several countries, can effectively trap SARS‐CoV‐2 virus‐like particles in fresh human airway mucus. IN‐006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN‐006 resulted in 100‐fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN‐006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS‐CoV‐2 and other respiratory pathologies.

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable “muco‐trapping” variant of motavizumab (Mota‐MT), a potent neutralizing mAb against RSV F is engineered. Mota‐MT traps RSV in AM via polyvalent Fc‐mucin bonds, reducing the fraction of fast‐moving RSV particles in both fresh pediatric and adult AM by ≈20–30‐fold in a Fc‐glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota‐MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota‐MT to RSV‐infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000‐fold and 100 000‐fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota‐MT‐treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco‐trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections. Respiratory syncytial virus (RSV) is the most common cause of hospitalizations in children under the age of 1. To date, there is no effective treatment for established RSV infections, only methods for prevention. In this research, the authors developed an inhaled anti‐RSV treatment that showed efficacy in mice, rats, and a neonatal lamb model of RSV infection, significantly reducing viral load and pathology compared to placebo‐treated animals.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries around the world, can effectively trap SARS-CoV-2 virus-like-particles in fresh human airway mucus. IN-006, a reformulation of Regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies. Competing Interest Statement MM, ZR, and JH are employees of Inhalon Biopharma/Mucommune, and hold shares in Inhalon Biopharma. HK, ML, CK, and KK are employees of Celltrion, Inc. SKL is founder of Mucommune, LLC and currently serves as its interim CEO. SKL is also founder of Inhalon Biopharma, Inc, and currently serves as its CSO as well as on its Board of Director and Scientific Advisory Board. SKL has equity interests in both Mucommune and Inhalon Biopharma; SKL's relationships with Mucommune and Inhalon are subject to certain restrictions under University policy. The terms of these arrangements are managed by UNC-CH in accordance with its conflict of interest policies.

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds 1 , 2 . In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated 3 . Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839–10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10 −13  s s −1 , which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star. The discovery of a long-period radio transient, GPM J1839–10, prompted a search of radio archives, thereby finding that this source has been repeating since at least 1988.

The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low frequency (80\\(-\\)300 MHz) southern sky. Since beginning operations in mid 2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21\\,cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together 60\\(+\\) programs recorded 20,000 hours producing 146 papers to date. In 2016 the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper we review the major results from the prior operation of the MWA, and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes, but also include ideas for directions outside these categories.

Recently several long-period radio transients have been discovered, with strongly polarised coherent radio pulses appearing on timescales between tens to thousands of seconds [1,2]. In some cases the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less well-sampled radio transients, is still debated [3]. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair production mechanisms, but such models do not easily predict radio emission from such slowly-rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 minutes) radio transient, which we have labeled GPMJ1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 seconds, and have quasi-periodic substructure. The observations prompted a search of radio archives, and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to \\(<3.610^-13\\)s s\\(^-1\\), which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

We report on observations of giant pulses from the Crab pulsar performed simultaneously with the Parkes radio telescope and the incoherent combination of the Murchison Widefield Array (MWA) antenna tiles. The observations were performed over a duration of approximately one hour at a center frequency of 1382 MHz with 340 MHz bandwidth at Parkes, and at a center frequency of 193 MHz with 15 MHz bandwidth at the MWA. Our analysis has led to the detection of 55 giant pulses at the MWA and 2075 at Parkes above a threshold of 3.5\\(\\) and 6.5\\(\\) respectively. We detected 51\\(\\%\\) of the MWA giant pulses at the Parkes radio telescope, with spectral indices in the range of \\(-3.6>> -4.9\\) (\\(S_ ^\\)). We present a Monte Carlo analysis supporting the conjecture that the giant pulse emission in the Crab is intrinsically broadband, the less than \\(100\\%\\) correlation being due to the relative sensitivities of the two instruments and the width of the spectral index distribution. Our observations are consistent with the hypothesis that the spectral index of giant pulses is drawn from normal distribution of standard deviation 0.6, but with a mean that displays an evolution with frequency from -3.00 at 1382 MHz, to -2.85 at 192 MHz.