SUMMARY Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe poxvirus infections, but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal Abs from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

We study gravitational wave production during Abelian gauge-field preheating following inflation. We consider both scalar and pseudoscalar inflaton models coupled directly to Abelian gauge fields via either a dilatonic coupling to the gauge-field kinetic term or an axial coupling to a Chern-Simons term. In both cases gravitational waves are produced efficiently during the preheating phase, with a signature louder than most cosmological signals. These gravitational waves can contribute to the radiation energy budget of Universe at a level which will be probed by upcoming cosmic microwave background experiments through N eff . For axially coupled fields the resulting gravitational wave spectrum is helically polarized-a unique feature that can be used to differentiate it from other stochastic gravitational wave backgrounds. We compute the gravitational topological charge and demonstrate that gauge preheating following axion inflation may be responsible for the matter-antimatter asymmetry of the Universe via gravitational leptogenesis.

We study gravitational wave production from gauge preheating in a variety of inflationary models, detailing its dependence on both the energy scale and the shape of the potential. We show that gauge preheating generically leads to a large gravitational wave background that contributes significantly to the effective number of relativistic degrees of freedom in the early Universe, N eff . We demonstrate that the efficiency of gravitational wave production is correlated with the tensor-to-scalar ratio, r.In particular, we show that efficient gauge preheating in models whose tensor-to-scalar ratio would be detected by next-generation cosmic microwave background experiments (r 10 −3 ) will either be detected through its contribution to N eff or ruled out. Furthermore, we show that bounds on N eff provide the most sensitive probe of the possible axial coupling of the inflaton to gauge fields regardless of the potential.

Epidemics generally spread through a succession of waves that reflect factors on multiple timescales. On short timescales, superspreading events lead to burstiness and overdispersion, whereas long-term persistent heterogeneity in susceptibility is expected to lead to a reduction in both the infection peak and the herd immunity threshold (HIT). Here, we develop a general approach to encompass both timescales, including time variations in individual social activity, and demonstrate how to incorporate them phenomenologically into a wide class of epidemiological models through reparameterization. We derive a nonlinear dependence of the effective reproduction number Re on the susceptible population fraction S. We show that a state of transient collective immunity (TCI) emerges well below the HIT during early, high-paced stages of the epidemic. However, this is a fragile state that wanes over time due to changing levels of social activity, and so the infection peak is not an indication of long-lasting herd immunity: Subsequent waves may emerge due to behavioral changes in the population, driven by, for example, seasonal factors. Transient and long-term levels of heterogeneity are estimated using empirical data from the COVID-19 epidemic and from real-life face-to-face contact networks. These results suggest that the hardest hit areas, such as New York City, have achieved TCI following the first wave of the epidemic, but likely remain below the long-term HIT. Thus, in contrast to some previous claims, these regions can still experience subsequent waves.

Scalar metric fluctuations generically source a spectrum of gravitational waves at second order in perturbation theory, poising gravitational wave experiments as potentially powerful probes of the small-scale curvature power spectrum. We perform a detailed study of the imprint of primordial non-Gaussianity on these induced gravitational waves, emphasizing the role of both the disconnected and connected components of the primoridal trispectrum. Specializing to local-type non-Gaussianity, we numerically compute all contributions and present results for a variety of enhanced primordial curvature power spectra.