Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)–specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.

This study investigates the effects of simultaneous inoculation of a selected Saccharomyces cerevisiae yeast strain with two different commercial strains of wine bacteria Oenococcus oeni at the beginning of the alcoholic fermentation on the kinetics of malolactic fermentation (MLF), wine chemical composition, and organoleptic characteristics in comparison with spontaneous MLF in Tempranillo grape must from Castilla-La Mancha (Spain). Evolution of MLF was assessed by the periodic analysis of L-malic acid through the enzymatic method, and most common physiochemical parameters and sensory traits were evaluated using a standardized sensory analysis. The samples were analyzed by GC/MS in SCAN mode using a Trace GC gas chromatograph and a DSQII quadrupole mass analyzer. Co-inoculation reduced the overall fermentation time by up to 2 weeks leading to a lower increase in volatile acidity. The fermentation-derived wine volatiles profile was distinct between the co-inoculated wines and spontaneous MLF and was influenced by the selected wine bacteria used in co-inoculation. Co-inoculation allows MLF to develop under reductive conditions and results in wines with very few lactic and buttery flavors, which is related to the impact of specific compounds like 2,3-butanedione. This compound has been also confirmed as being dependent on the wine bacteria used.

H5Nx viruses continue to wreak havoc in avian and mammalian species worldwide. The virus distinguishes itself by the ability to replicate to high titers and transmit efficiently in a wide variety of hosts in diverse climatic environments. Fortunately, transmission to and between humans is scarce. Yet, if such an event were to occur, it could spark a pandemic as humans are immunologically naïve to H5 viruses. A significant determinant of transmission to and between humans is the ability of the influenza A virus hemagglutinin (HA) protein to shift from an avian-type to a human-type receptor specificity. Here, we demonstrate that a 2016 2.3.4.4e virus HA can convert to human-type receptor binding via a single Q226L mutation, in contrast to a cleavage-modified 2016 2.3.4.4b virus HA. Using glycan arrays, X-ray structural analyses, tissue- and direct glycan binding, we show that L133a Δ and 227Q are vital for this phenotype. Thus, whereas the 2.3.4.4e virus HA only needs a single amino acid mutation, the modified 2016 2.3.4.4b HA was not easily converted to human-type receptor specificity.

Certain acetic and lactic acid bacteria are major causes of quality defects in musts and wines, giving rise to defects such as a “vinegary,” “sharp, like nail polish-remover” taste or preventing alcoholic and/or malolactic fermentation. Sulfur dioxide is the major tool currently used in the control of these bacteria in wine. The aim of this work was to isolate bacteriophages from musts and wine of different grape varieties that were able to eliminate lactic and acetic acid bacteria spoilages at the laboratory scale. Musts obtained from grape-berries of Vitis vinifera cv. Chardonnay and Moscatel and a red wine made with V. vinifera cv. Tintilla de Rota were used to isolate bacteriophages. Bacteriophages were obtained from each of the musts and the wine and belonged to the order Caudovirals and the family Tectivirals. They were isolated by classical virology methods and identified by electron microscopy. The host bacteria used in the study were lactic acid bacteria of the species Lactobacillus hilgardii, Lactobacillus plantarum, and Oenococcus oeni and the acetic bacteria Acetobacter aceti. A comparative study was performed by adding phage titrations and SO₂ to musts and wines, which had been previously inoculated with bacteria, to study the effectiveness of bacteriophages against bacteria. The comparative study showed that some bacteriophages were as effective as sulfur dioxide at low concentrations.

Acetic and some lactic acid bacteria are the main reason for the loss of quality of musts and wines, giving rise to defects such as “vinegary”, “chopped” or preventing alcoholic and / or malolactic fermentation. The solution to this problem consists in the application of authorized bactericidal agents, such as sulfurous. The aim of this work is to isolate bacteriophages from musts and wines of different grape varieties, able to eliminate lactic and acetic acid bacteria spoilages. Musts obtained from grape-berries of Vitis vinifera cv. Chardonnay and Moscatel and a red wine made with the Tintilla de Rota variety were used to isolate bacteriophages. It were isolated by classical virology methods and identified by electron microscopy. Host bacteria used in the study were the lactic acid bacteria of the species Lactobacillus hilgardii, L. plantarum and Oenococcus oeni and the acetic bacteria Acetobacter aceti. A comparative study was performed on musts and wines, previously inoculated with bacteria, by phage titration and SO₂ addition to study the effectiveness of bacteriophages against bacteria. Bacteriophages were obtained from all musts and wine, belonging to the order of Caudovirals and Tectivirals. The comparative study showed that a cocktail of bacteriophages at low concentration is as effective as sulfur.

The multivalent display of surface glycoprotein hemagglutinin (HA) on Influenza A viruses (IAVs) enhances the overall binding avidity to sialylated glycans on host cell surfaces. While precomplexing HA trimers with antibodies increases multivalency and avidity, this method does not replicate the virion's geometry and limits insights into the multivalent binding process. Here, we use perfectly controllable icosahedral protein nanoparticles to examine the multivalent HA receptor-binding properties. We compare three HA presentation systems with varying degrees of multivalency: single HA trimers, antibody-precomplexed HA trimers, and HA trimers on nanoparticles. Our results indicate that increasing HA valency enhances binding avidity across various glycan surfaces, including erythrocytes, cells, and lipid bilayers with varying glycan densities, while maintaining receptor specificity. By combining functional and non-functional HA trimers within the nanoparticle formation process, we create statistical mixtures of nanoparticles with varying valencies. At high receptor densities, nanoparticles with few functional trimers still bind strongly, whereas at low receptor densities, a patch of five HA trimers appears necessary for binding. As a key finding, we observe that such a statistical mixture of nanoparticles with functional and nonfunctional HAs binds to glycan surfaces in a stronger density-dependent manner than fully functional particles. We also observe differences in binding modes that correlate with the number of functional trimers, the glycan structure (linear vs branched), and the densities achievable with these glycans. Overall, our findings demonstrate that the presentation of multivalent HA plays an enormous role in the response to glycan receptor type and density, with implications for the future design of virus monitoring, viral inhibitors, and targeting vectors.