Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

<p>Abstract</p> <p>Background</p> <p>The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?</p> <p>Methods</p> <p>We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.</p> <p>Results</p> <p>Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).</p> <p>Conclusions</p> <p>Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.</p

Cupricyclins, Novel Redox-Active Metallopeptides Based on Conotoxins Scaffold

Highly stable natural scaffolds which tolerate multiple amino acid substitutions represent the ideal starting point for the application of rational redesign strategies to develop new catalysts of potential biomedical and biotechnological interest. The knottins family of disulphide-constrained peptides display the desired characteristics, being highly stable and characterized by hypervariability of the inter-cysteine loops. The potential of knottins as scaffolds for the design of novel copper-based biocatalysts has been tested by engineering a metal binding site on two different variants of an ω-conotoxin, a neurotoxic peptide belonging to the knottins family. The binding site has been designed by computational modelling and the redesigned peptides have been synthesized and characterized by optical, fluorescence, electron spin resonance and nuclear magnetic resonance spectroscopy. The novel peptides, named Cupricyclin-1 and -2, bind one Cu2+ ion per molecule with nanomolar affinity. Cupricyclins display redox activity and catalyze the dismutation of superoxide anions with an activity comparable to that of non-peptidic superoxide dismutase mimics. We thus propose knottins as a novel scaffold for the design of catalytically-active mini metalloproteins