Egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines

Egg-derived viruses are the only available seed material for influenza vaccine production. Vaccine manufacturing is done in embryonated chicken eggs, MDCK or Vero cells. In order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. We demonstrate that H3N2 egg-derived seed viruses (A/Brisbane/10/07, IVR147, and A/Uruguay/716/07) triggered the hemagglutinin (HA) conformational change under less acidic conditions (0.2-0.6 pH units) than antigenically similar primary isolates. This phenotype was associated with HA1 (A138S, L194P) and HA2 (D160N) substitutions, and strongly related to decreased virus stability towards acidic pH and elevated temperature. The subsequent propagation of H3N2 and H1N1 egg-derived seed viruses in MDCK and Vero cells induced HA2 N50K (H1N1) and D160E (H3N2) mutations, improving virus growth in cell culture but further impairing virus stability. The prevention of the loss or recovery of stability was possible by cultivation at acidified conditions. Viruses carrying less stable HAs are more sensitive for HA conformational change during concentration, purification and storage. This results in decreased detectable HA antigen content - the main potency marker for inactivated influenza vaccines. Thus, virus stability can be a useful marker for predicting the manufacturing scope of seed viruses

Phase diagram of the heavy fermion system YbFe/sub 2/Ge/sub 2/ under pressure

The phase diagram of the heavy fermion compound YbFe2Ge2 under high pressures P ≤ 18.2 GPa was obtained by electrical resistivity measurements. Pressure drives the system from a paramagnetic Fermi liquid state to a magnetically ordered state, with a quantum critical point at PC ≈ 9.4 GPa. In the vicinity of PC a non-Fermi-liquid behavior ascribed to two-dimensional antiferromagnetic fluctuations is observed. In the magnetic side, the resistivity shows the existence of spin-wave excitations characteristic of an antiferromagnet

Phase diagram of the heavy fermion system YbFe/sub 2/Ge/sub 2/ under pressure

The phase diagram of the heavy fermion compound YbFe2Ge2 under high pressures P ≤ 18.2 GPa was obtained by electrical resistivity measurements. Pressure drives the system from a paramagnetic Fermi liquid state to a magnetically ordered state, with a quantum critical point at PC ≈ 9.4 GPa. In the vicinity of PC a non-Fermi-liquid behavior ascribed to two-dimensional antiferromagnetic fluctuations is observed. In the magnetic side, the resistivity shows the existence of spin-wave excitations characteristic of an antiferromagnet

Very‐low‐carbohydrate diet enhances human T‐cell immunity through immunometabolic reprogramming

Abstract Very‐low‐carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno‐nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T‐cell responses. CD4+, CD8+, and regulatory T‐cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very‐low‐carbohydrate diet as a clinical tool to improve human T‐cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required