Biology subjects

Cappelletti, M.

Publications and source records attributed to Cappelletti, M..

5 recordsLinked to original sources

bioRxiv2026

IL1 blockade attenuates E. coli induced intrauterine inflammation and preterm labor in Rhesus macaques

Intrauterine infection and inflammation are major causes of preterm labor, yet antibiotics alone often fail to prevent preterm birth despite achieving microbial clearance. Interleukin1 (IL1) is a key mediator of intra-amniotic inflammation and functional progesterone withdrawal, processes linked to labor initiation. We tested whether IL1 blockade with the clinically approved IL1 receptor antagonist, anakinra, could reduce inflammation and preterm labor in a Rhesus macaque model of intra-amniotic Escherichia coli infection followed by delayed antibiotic treatment. Here we show that anakinra reduced the incidence of preterm labor by 40% (p=0.07), attenuated inflammation in the fetal membranes and cervix, and preserved progesterone receptor-B abundance in the fetal membranes. These effects were most pronounced in animals protected from preterm labor. Our findings in a relevant model support the translational potential of combining IL1 blockade with antibiotics for infection-associated preterm labor. One sentence summaryRecombinant human IL1 receptor antagonist (anakinra) decreased E. coli infection induced preterm labor and partially decreased intrauterine inflammation in a non-human primate model of inflammation mediated preterm labor.

immunology↗

bioRxiv2025

Genomic evidence for atmospheric chemosynthesis as a defining trait of Ktedonobacteria inhabiting subterranean environments

Members of the class Ktedonobacteria (phylum Chloroflexota) are widespread across a variety of terrestrial environments. They are particularly enriched in silica-rich oligotrophic caves, where they may act as early colonizers, but the genomic bases supporting this pioneering capacity are still unclear. Here, we present a systematic genomic analysis of Ktedonobacteria from diverse ecosystems, with a focus on oligotrophic caves. Cave Ktedonobacteria belong to novel genera of Ktedonobacteraceae and harbor genes supporting a mixotrophic metabolism that combines the use of organic and inorganic substrates as energy and carbon sources. Comparative analyses of all available Ktedonobacteria genomes from diverse environments showed that most metabolic traits, including those enabling atmospheric gas oxidation, are primarily driven by taxonomy. In contrast, genes involved in CO2 fixation are enriched in Ktedonobacteria inhabiting caves. Phylogenetic analysis showed that the RuBisCO of Ktedonobacteria likely represents a novel Form I subtype, which we designate as BAK, reflecting its wide occurrence in thermophilic and acidophilic Bacillota and Actinomycetota inhabiting similar extreme environments. The presence of this subtype across distinct lineages in comparable habitats suggests that it may confer a selective advantage in nutrient-poor settings (like caves) and that its distribution may be subject to horizontal gene transfer. This autotrophic capacity relies on a transaldolase variant of the Calvin-Benson-Bassham cycle that was previously described only in one Firmicutes species. Overall, this study provides genetic evidence supporting the combination of atmospheric gas oxidation with dark CO2 fixation in Ktedonobacteria, highlighting their role as primary producers in oligotrophic ecosystems, including caves.

microbiology↗

bioRxiv2021

COVID-eVax, an electroporated plasmid DNA vaccine candidate encoding the SARS-CoV-2 Receptor Binding Domain, elicits protective immune responses in animal models of COVID-19

The COVID-19 pandemic caused by the {beta}-coronavirus SARS-CoV-2 has made the development of safe and effective vaccines a critical global priority. To date, four vaccines have already been approved by European and American authorities for preventing COVID-19 but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle, a technology previously utilized for cancer vaccines. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 Spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax - a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein RBD - induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function and significantly lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started in Italy.

immunology↗

bioRxiv2021

Characterizing the middle-age neurophysiology using EEG/MEG

Middle adulthood - the period of life between 40 and 60 years of age - is accompanied by important physical and emotional changes, as well as cognitive and neuronal ones. Nevertheless, middle age is often overlooked in neuroscience under the assumption that this is a time of relative stability, although cognitive decline, as well as changes in brain structure and function are well-established by the age of 60. Here we characterized the middle-aged brain in the context of healthy younger and older adults by assessing resting-state electrophysiological and neuromagnetic activity in two different samples (N = 179, 631). Alpha and beta oscillations - two key ageing signatures - were analyzed in terms of spectral power and burst events. While posterior alpha power and burst rate features changed linearly with age, similarly to behavioral measures, sensorimotor beta power and burst rate properties varied non-linearly, with inflection points during middle age. The findings suggest that ageing is characterized by distinct spatial and temporal brain dynamics, some critically arising in middle age.

neuroscience↗

bioRxiv2021

The intensity of the immune response to LPS and E. coli regulates the induction of preterm labor in Rhesus Macaques

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed Rhesus macaque models of IUI driven by lipopolysaccharyde (LPS) or live E. coli. PTL did not occur in LPS challenged Rhesus macaque while E. coli infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli infected animals showed higher levels of inflammatory mediators, particularly IL6 and prostaglandins, in the chorioamnion decidua and amniotic fluid. Neutrophil infiltration in the chorion was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNASeq analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon response, chemotaxis, sumoylation and iron homeostasis were upregulated in the E. coli group compared to the LPS group. Our data suggest that intensity of the host immune response to IUI may determine susceptibility to PTL.

immunology↗