Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

We present an attempt to estimate the long-term changes of Relative Sea Level (RSL) and the different factors contributing to such trends on a local and regional scale using a statistical linear model. The time series analysed correspond to 17 tide-gauges grouped in three different areas: the northern and western Atlantic coasts of the Iberian Peninsula, the Canary Islands, and the southern and eastern coasts of the Iberian Peninsula and Balearic Islands. The analysis was performed for two periods: 1948-2019, using tide-gauge data, and 1993-2019, using both tide-gauge and altimetry data for comparison. The trends for the period 1948-2019 ranged between 1.09 0.14 (Canary Islands) and 2.05 0.21 mm/yr, for the northern and western Atlantic Iberian Peninsula. Altimetry data during the period 1993-2019 yielded quite homogeneous results for all the locations and regions, ranging between 2.7 0.4 and 3.0 0.3 mm/yr. On the contrary, the results obtained from tide-gauge data for this recent period showed a large dispersion, very likely due to local effects or even levelling or instrumental errors. Nevertheless, when the results were averaged for each area, the observed trends were comparable to the altimetry results, with values of 2.3 0.8, 2.7 0.5 and 2.8 0.8 mm/yr for the three regions of study. A stepwise forward linear regression has been used to relate the observed RSL variability to the atmospheric forcing and the thermosteric and halosteric components of the sea level. Surprisingly, the thermosteric and halosteric contributions were not significantly correlated to the observed RSL in many cases, and consequently the steric, the total addition of mass, the mass of salt, and the freshwater contributions to the observed sea level trends could not be reliably estimated. This result seems to be the consequence of the scarcity of temperature and salinity data. This hypothesis is confirmed by the exception of L’Estartit tide-gauge. This location is close to a well sampled region. In this case, the atmospheric variables and the thermosteric and halosteric terms explained the 80 % of the observed RSL variance and the contributions of these terms could be estimated. The freshwater contribution for this location was between 1.3 and 1.4 mm/yr, consistent with recent estimations of the contributions of glaciers and Greenland and Antarctica Ice Sheets. These results highlight the importance of monitoring programs and routine sampling for the determination of the different factors contributing to the sea level variability.

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.