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Biology subjects

Socol, Y.

Publications and source records attributed to Socol, Y..

2 recordsLinked to original sources

Theoretical value of radiation priming for mitigating toxicity in radiation therapy

The relevance of ionizing radiation effects is high in the field of radiation oncology. Namely, radiation toxicity is a crucial limiting factor in dose administration. To address this concern, by adopting an empirical approach it is possible to uncover certain truths that might not be attainable through rigorous biophysical analysis, as the human body represents a complex system. That is, even possessing complete knowledge of interactions between its elementary units (cells) may prove insufficient in explaining the overall systems reactions. An empirical mathematical model for adaptive biological response to time-dependent irradiation of arbitrary time-shapes was developed. The model was based on the damped-oscillator analogy from physics. The research reported here is a generalization of the damped-oscillator model by introducing a biologically relevant inverted Gompertzian-like shape, rather commonly employed in adaptive response modeling, with practical implications for biologists and oncologists. Based on the developed model, a practical approach is suggested to improve radiation therapy protocols by radiation training (priming) through administration of low, gradually increasing total-body irradiation doses. Following this priming, individuals should be capable of withstanding higher therapeutic doses, maybe up to five times the regular amount. Initial estimations propose a training time of approximately six weeks and a training dose of up to approximately 600 cGy. If the model is correct, effectiveness of radiation therapy can be significantly improved by radiation priming, since administration of considerably higher therapeutic doses would be enabled through priming procedures.

cancer biology↗

Intramuscular mRNA BNT162b2 vaccine against SARS-CoV-2 induces robust neutralizing salivary IgA

Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable sterilizing immunity at the mucosal level. Our study uncovers, strong neutralizing mucosal component (NT50 [≤] 50pM), emanating from intramuscular administration of an mRNA vaccine. We show that saliva of BNT162b2 vaccinees contains temporary IgA targeting the Receptor-Binding-Domain (RBD) of SARS-CoV-2 spike protein and demonstrate that these IgAs are key mediators of potent neutralization. RBD-targeting IgAs were found to associate with the Secretory Component, indicating their bona-fide transcytotic origin and their dimeric tetravalent nature. The mechanistic understanding of the exceptionally high neutralizing activity provided by mucosal IgA, acting at the first line of defence, will advance vaccination design and surveillance principles, pointing to novel treatment approaches, and to new routes of vaccine administration and boosting. Significance statementWe unveiled powerful mucosal neutralization upon BNT162b2 vaccination, mediated by temporary polymeric IgA and explored its longitudinal properties. We present a model, whereby the molecular architecture of polymeric mucosal IgA and its spatial properties are responsible for the outstanding SARS-CoV-2 neutralization potential. We established a methodology for quantitative comparison of immunoreactivity and neutralization for IgG and IgAs in serum and saliva in molar equivalents for standardization in diagnostics, surveillance of protection and for vaccine evaluations.

microbiology↗