Mosquito thermal tolerance is remarkably constrained across a large climatic range.

How mosquitoes may respond to rapid climate warming remains unknown for most species, but will have major consequences for their future distributions, with cascading impacts on human well-being, biodiversity and ecosystem function. We investigated the adaptive potential of a wide-ranging mosquito species, Aedes sierrensis, across a large climatic gradient by conducting a common garden experiment measuring the thermal limits of mosquito life-history traits. Although field-collected populations originated from vastly different thermal environments that spanned over 1200 km, we found limited variation in upper thermal tolerance between populations. In particular, the upper thermal limits of all life-history traits varied by less than 3°C across the species range and, for most traits, did not differ significantly between populations. For one life-history trait-pupal development rate-we did detect significant variation in upper thermal limits between populations, and this variation was strongly correlated with source temperatures, providing evidence of local thermal adaptation for pupal development. However, we found that maximum environmental temperatures across most of the species' range already regularly exceed the highest upper thermal limits estimated under constant temperatures. This result suggests that strategies for coping with and/or avoiding thermal extremes are likely key components of current and future mosquito thermal tolerance.

Elucidating allergic reaction mechanisms in response to SARS-CoV-2 mRNA vaccination in adults.

BACKGROUND: During the COVID-19 pandemic, novel nanoparticle-based mRNA vaccines were developed. A small number of individuals developed allergic reactions to these vaccines although the mechanisms remain undefined. METHODS: To understand COVID-19 vaccine-mediated allergic reactions, we enrolled 19 participants who developed allergic events within 2 h of vaccination and 13 controls, nonreactors. Using standard hemolysis assays, we demonstrated that sera from allergic participants induced stronger complement activation compared to nonallergic subjects following ex vivo vaccine exposure. RESULTS: Vaccine-mediated complement activation correlated with anti-polyethelyne glycol (PEG) IgG (but not IgM) levels while anti-PEG IgE was undetectable in all subjects. Depletion of total IgG suppressed complement activation in select individuals. To investigate the effects of vaccine excipients on basophil function, we employed a validated indirect basophil activation test that stratified the allergic populations into high and low responders. Complement C3a and C5a receptor blockade in this system suppressed basophil response, providing strong evidence for complement involvement in vaccine-mediated basophil activation. Single-cell multiome analysis revealed differential expression of genes encoding the cytokine response and Toll-like receptor (TLR) pathways within the monocyte compartment. Differential chromatin accessibility for IL-13 and IL-1B genes was found in allergic and nonallergic participants, suggesting that in vivo, epigenetic modulation of mononuclear phagocyte immunophenotypes determines their subsequent functional responsiveness, contributing to the overall physiologic manifestation of vaccine reactions. CONCLUSION: These findings provide insights into the mechanisms underlying allergic reactions to COVID-19 mRNA vaccines, which may be used for future vaccine strategies in individuals with prior history of allergies or reactions and reduce vaccine hesitancy.