Multiparameter Telemetry as a Sensitive Screening Method to Detect Vaccine Reactogenicity in Mice

Refined vaccines and adjuvants are urgently needed to advance immunization against global infectious challenges such as HIV, hepatitis C, tuberculosis and malaria. Large-scale screening efforts are ongoing to identify adjuvants with improved efficacy profiles. Reactogenicity often represents a major hurdle to the clinical use of new substances. Yet, irrespective of its importance, this parameter has remained difficult to screen for, owing to a lack of sensitive small animal models with a capacity for high throughput testing. Here we report that continuous telemetric measurements of heart rate, heart rate variability, body core temperature and locomotor activity in laboratory mice readily unmasked systemic side-effects of vaccination, which went undetected by conventional observational assessment and clinical scoring. Even minor aberrations in homeostasis were readily detected, ranging from sympathetic activation over transient pyrogenic effects to reduced physical activity and apathy. Results in real-time combined with the potential of scalability and partial automation in the industrial context suggest multiparameter telemetry in laboratory mice as a first-line screen for vaccine reactogenicity. This may accelerate vaccine discovery in general and may further the success of vaccines in combating infectious disease and cancer

The electrochemical reduction of Sn(II) at the dropping mercury electrode from aqueous 1 M sulfuric acid and from 0.3 M phenolsulphonic acid and its inhibition by ensa-6

By means of the demodulation technique for the first time the high reduction rate constant of the Sn(II) ion in sulfuric acid is obtained. From the value of the operational transfer coefficient it follows that a following, potential independent “chemical” step is rate determining. On the addition of an inhibitor at positive potentials the transfer of the first electron can be made slow because this process is inhibited much more strongly than the following chemical step. At high concentration of the inhibitor the first electron transfer is rate determining at all potentials. In phenolsulphonic acid as the base electrolyte it appears that an intermediate chemical step is rate controlling together with the following chemical step. The intermediate step could be made rate determining by adding a little of the inhibitor. With a high concentraton of the inhibitor the first electron transfer becomes rate controlling again. Also the reduction of Sn(II) from a practical plating bath is discussed

On second order effects in a galvanic cell : Part I. Polarization by a sine wave modulated high frequency current

A theoretical study is presented concerning the application of a high-frequency alternating current, amplitude modulated by a low-frequency sine wave, to a galvanic cell. Based on the correlation with the faradaic rectification technique, expressions are given for the low-frequency demodulation voltages of the faradaic process and for the double-layer capacity. Both responses, which are in-phase with the modulation signal, are combined by considering them as voltage sources, having respectively the faradaic impedance and the double-layer impedance as internal impedances. The resulting demodulation voltage appears to possess an in-phase and a quadrature component, from which information can be obtained of the high-frequency as well as the low-frequency behaviour of the cell

Complex plane analysis of single pulse data

The evaluation of kinetic parameters from galvanostatic and coulostatic step measurements is performed in a new way. The experimental overvoltage/time curve is written as an analytical function and transformed into the Laplace domain. This implicates that the variable time has been replaced by the operational frequency, s, which is given a completely imaginary value, jω. Both the real and imaginary components of the complex electrode impedance can be easily computed for any chosen value of the angular frequency, ω. Subsequent analysis according to the complex plane method delivers the desired information. The procedure is illustrated by application to data obtained with the Cd2+/Cd(Hg) electrode in 1 M Na2SO4 at pH 4

On the elucidation of mechanisms of electrode reactions by combination of a.c.-and faradaic rectification polarography. Application to the Zn2+/Zn(Hg) and Cd2+/Cd(Hg) reduction

The theory of faradaic rectification polarography is extended to systems of higher order stoichiometry. The couples Zn2+/Zn(Hg) in 0.5 M MgSO4 and Cd2+/Cd(Hg) in 1 M KCl are studied with the aid of this technique in a wide potential range. The Zn2+/Zn reaction is interpreted as a multistep mechanism. The Cd2+/Cd reaction did not appear to be a simple linear reaction. Some higher order mechanisms are tested using the measurement

The electrochemical reduction of oxygen to hydrogen peroxide at the dropping mercury electrode : Part II. Its kinetics at 0.4<=pH<=5.9

From experiments in acidic solutions it is shown that though the mechanism found in alkaline and neutral solutions (Part I) remains valid, the rate constant of the protonation step of the superoxide ion becomes pH-dependent. The experimental results can be quantitatively explained on the assumption of simultaneous protonation by water and free protons, the rate constants of electron transfer and protonation by water retaining their value. Therefore, the kinetics of the reduction of oxygen can be described by four parameters only, in the range 0.4≤pH≤12.5. The applicability of some other conceivable mechanisms is discussed

The analysis of electrode impedances complicated by the presence of a constant phase element

The electrical double-layer at a solid electrode does not in general behave as a pure capacitance but rather as an impedance displaying a frequency-independent phase angle different from 90°. Ways are indicated how to analyse the interfacial impedance if such a complication arises in the presence of a faradaic process, both on the supposition that the double-layer behaviour is due to surface inhomogeneity and on the supposition that it is a double-layer property per se. As examples, the equations derived are successfully applied to a totally irreversible and an ac quasi-reversible electrode process at a gold electrode