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Abstract SARS-CoV-2 lipid nanoparticle mRNA vaccines continue to be administered as the predominant prophylactic measure to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series (first two doses) and a subset of 137 individuals who then received an mRNA-based booster dose. We find the booster dose elicits a 71–84% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses decreases with age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further, we find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis test we find no difference between male and female humoral decay kinetics, however, a multivariate approach utilizing Least Absolute Shrinkage and Selection Operator (LASSO) regression for feature selection reveals a statistically significant (p $$

Abstract Inspired by biology, great progress has been made in creating artificial molecular motors. However, the dream of harnessing proteins – the building blocks selected by nature – to design autonomous motors has so far remained elusive. Here we report the synthesis and characterization of the Lawnmower, an autonomous, protein-based artificial molecular motor comprised of a spherical hub decorated with proteases. Its “burnt-bridge” motion is directed by cleavage of a peptide lawn, promoting motion towards unvisited substrate. We find that Lawnmowers exhibit directional motion with average speeds of up to 80 nm/s, comparable to biological motors. By selectively patterning the peptide lawn on microfabricated tracks, we furthermore show that the Lawnmower is capable of track-guided motion. Our work opens an avenue towards nanotechnology applications of artificial protein motors.

Abstract The lipid nanoparticle (LNP)-formulated mRNA vaccines BNT162b2 and mRNA-1273 are a widely adopted multi vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogenicity of the vaccine, albeit within a limited study time frame. Here, we use a within-host mathematical model for LNP-formulated mRNA vaccines, informed by available clinical trial data from 2020 to September 2021, to project a longer term understanding of immunity as a function of vaccine type, dosage amount, age, and sex. We estimate that two standard doses of either mRNA-1273 or BNT162b2, with dosage times separated by the company-mandated intervals, results in individuals losing more than 99% humoral immunity relative to peak immunity by 8 months following the second dose. We predict that within an 8 month period following dose two (corresponding to the original CDC time-frame for administration of a third dose), there exists a period of time longer than 1 month where an individual has lost more than 99% humoral immunity relative to peak immunity, regardless of which vaccine was administered. We further find that age has a strong influence in maintaining humoral immunity; by 8 months following dose two we predict that individuals aged 18–55 have a four-fold humoral advantage compared to aged 56–70 and 70+ individuals. We find that sex has little effect on the immune response and long-term IgG counts. Finally, we find that humoral immunity generated from two low doses of mRNA-1273 decays at a substantially slower rate relative to peak immunity gained compared to two standard doses of either mRNA-1273 or BNT162b2. Our predictions highlight the importance of the recommended third booster dose in order to maintain elevated levels of antibodies.

Summary: Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were ‘rescued’ post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.

During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration so that supply constraints issues are diminished. These include increasing the time between consecutive doses in a two-dose vaccine regimen and reducing the dosage of the second dose. We consider both of these strategies in a mathematical modeling study of a non-replicating viral vector adenovirus vaccine in this work. We investigate the impact of different prime-boost strategies by quantifying their effects on immunological outcomes based on simple system of ordinary differential equations. The boost dose is administered either at a standard dose (SD) of 1000 or at a low dose (LD) of 500 or 250 vaccine particles. Results show dose-dependent immune response activity. Our model predictions show that by stretching the prime-boost interval to 18 or 20, in an SD/SD or SD/LD regimen, the minimum promoted antibody (Nab) response will be comparable with the neutralizing antibody level measured in COVID-19 recovered patients. Results also show that the minimum stimulated antibody in SD/SD regimen is identical with the high level observed in clinical trial data. We conclude that an SD/LD regimen may provide protective capacity, which will allow for conservation of vaccine doses.

The mean-squared displacement (MSD) is an averaged quantity widely used to assess anomalous diffusion. In many cases, such as molecular motors with finite processivity, the dynamics of the system of interest produce trajectories of varying duration. Here, we explore the effects of finite processivity on different measures of the MSD. We do so by investigating a deceptively simple dynamical system: a one-dimensional random walk (with equidistant jump lengths, symmetric move probabilities, and constant step duration) with an origin-directed detachment bias. By tuning the time dependence of the detachment bias, we find through analytical calculations and trajectory simulations that the system can exhibit a broad range of anomalous diffusion, extending beyond conventional diffusion to superdiffusion and even superballistic motion. We analytically determine that protocols with a time-increasing detachment lead to an ensemble-averaged velocity increasing in time, thereby providing the effective acceleration that is required to push the system above the ballistic threshold. An MSD analysis of burnt-bridges ratchets similarly reveals superballistic behavior. Because superdiffusive MSDs are often used to infer biased, motorlike dynamics, these findings provide a cautionary tale for dynamical interpretation.