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Biology subjects

Straus, S.

Publications and source records attributed to Straus, S..

4 recordsLinked to original sources

mRNA Vaccine-Induced SARS-CoV-2 Spike-Specific IFN-γ and IL-2 T-cell Responses are Predictive of Serological Neutralization and are Transiently Enhanced by Pre-Existing Cross-Reactive Immunity

The contributions of SARS-CoV-2-specific T-cells to vaccine efficacy and durability are unclear. We investigated the relationships between mRNA vaccine-induced spike-specific IFN-{gamma} and IL-2 T-cell responses, anti-spike/RBD IgG/IgA antibodies, and live virus neutralizing capacity in long-term-care-home staff doubly vaccinated with BNT162b2 or mRNA-1273. The impacts of pre-existing cross-reactive T-cell immunity to SARS-CoV-2 on cellular and humoral responses to vaccination were additionally assessed. Mathematical modelling of the kinetics of spike-specific IFN-{gamma} and IL-2 T-cell responses over 6-months post-second dose was bifurcated into recipients who exhibited gradual increases (54% and 42%, respectively) with doubling times of 173 days, or decreases (46% and 58%, respectively) with half-lives of 115 days. Differences in kinetics did not correlate with any clinical phenotypes, although increases were proposed to be due to subclinical viral exposures. Serological anti-spike/RBD IgG/IgA antibody levels had otherwise decayed in all participants with half-lives of 55, 53, 76, and 59 days, respectively. Spike-specific T-cell responses induced at 2-6 weeks correlated with live viral neutralization at 6-months post-second dose, especially in hybrid immune individuals. Participants with pre-existing cross-reactive T-cell immunity to SARS-CoV-2 exhibited greater spike-specific T-cell responses, reduced anti-RBD IgA antibody levels, and a trending increase in neutralization at 2-6 weeks post-second dose. Non-spike-specific T-cells predominantly targeted SARS-CoV-2 non-structural protein at 6-months post-second dose in cross-reactive participants. mRNA vaccination was lastly shown to induce off-target T-cell responses against unrelated antigens. In summary, vaccine-induced spike-specific T-cell immunity appeared to influence serological neutralizing capacity, with only a modest effect induced by pre-existing cross-reactivity. IMPORTANCEOur findings provide important insights on the potential contributions of mRNA vaccine-induced spike-specific T-cell responses to the durability of neutralizing antibody levels in both uninfected and hybrid immune recipients. Our study additionally sheds light on the precise impacts of pre-existing cross-reactive T-cell immunity to SARS-CoV-2 on the magnitude and kinetics of cellular and humoral responses to vaccination. This study should ultimately inform the development of novel pan-coronavirus vaccines and vaccine regimens that can maximize the durability and breadth of protection against both current and future human coronaviruses of concern.

immunology↗

Temperature impacts on dengue incidence are nonlinear and mediated by climatic and socioeconomic factors

Temperature can influence mosquito-borne diseases like dengue. These effects are expected to vary geographically and over time in both magnitude and direction and may interact with other environmental variables, making it difficult to anticipate changes in response to climate change. Here, we investigate global variation in temperature-dengue relationship by analyzing published correlations between temperature and dengue and matching them with remotely sensed climatic and socioeconomic data. We found that the correlation between temperature and dengue was most positive at intermediate (near 24{degrees}C) temperatures, as predicted from the thermal biology of the mosquito and virus. Positive temperature-dengue associations were strongest when temperature variation and population density were high and decreased with infection burden and rainfall mean and variation, suggesting alternative limiting factors on transmission. Our results show that while climate effects on diseases are context-dependent they are also predictable from the thermal biology of transmission and its environmental and social mediators.

ecology↗

Macroecological variation in movement profiles: body size does not explain it all

Animals couple habitats by three types of movement: dispersal, migration, and foraging, which dynamically link populations, communities, and ecosystems. Spatial distances of movement tend to correlate with each other, reflecting shared allometric scaling with body size, but may diverge due to biomechanical, phylogenetic, and ecological constraints. While these constraints have been investigated within specific taxa, the macroecological and macroevolutionary constraints on movement distances, and causes of those constraints, are still unknown. Here, we synthesized distances of all three movement types across 300+ vertebrate species, and investigated how the relationships between movement types and body size were modified by movement medium, taxonomy, and trophic guild (carnivore, herbivore, etc.). We found that the strength of relationships between movement types and body size varied among environments, taxa, and trophic guilds. Movement profiles interacted with physiological, taxonomic, and ecological traits to depart from expected body mass scaling. Overall, we find that there are systematic patterns to movement distances, and that movement types with very distinct ecological consequences (foraging, migration) can be correlated and subject to similar constraints. This implies that the scales of population dynamics in ecological communities are not entirely determined by the environment and likely reflect general biomechanical, evolutionary and metabolic constraints.

ecology↗

Female grant applicants are equally successful when peer reviewers assess the science, but not when they assess the scientist

BackgroundPrevious research shows that men often receive more research funding than women, but does not provide empirical evidence as to why this occurs. In 2014, the Canadian Institutes of Health Research (CIHR) created a natural experiment by dividing all investigator-initiated funding into two new grant programs: one with and one without an explicit review focus on the caliber of the principal investigator.\n\nMethodsWe analyzed application success among 23,918 grant applications from 7,093 unique principal investigators in a 5-year natural experiment across all investigator-initiated CIHR grant programs in 2011-2016. We used Generalized Estimating Equations to account for multiple applications by the same applicant and an interaction term between each principal investigators self-reported sex and grant programs to compare success rates between male and female applicants under different review criteria.\n\nResultsThe overall grant success rate across all competitions was 15.8%. After adjusting for age and research domain, the predicted probability of funding success in traditional programs was 0.9 percentage points higher for male than for female principal investigators (OR 0.934, 95% CI 0.854-1.022). In the new program focused on the proposed science, the gap was 0.9 percentage points in favour of male principal investigators (OR 0.998, 95% CI 0.794-1.229). In the new program with an explicit review focus on the caliber of the principal investigator, the gap was 4.0 percentage points in favour of male principal investigators (OR 0.705, 95% CI 0.519- 0.960).\n\nInterpretationThis study suggests gender gaps in grant funding are attributable to less favourable assessments of women as principal investigators, not differences in assessments of the quality of science led by women. We propose ways for funders to avoid allowing gender bias to influence research funding.\n\nFundingThis study was unfunded.

scientific communication and education↗