Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. Co-culturing CD4 <sup>+</sup> with autologous CD8 <sup>+</sup> T cells from ART-suppressed HIV <sup>+</sup> donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 <sup>+</sup> T cells. This trispecific antibody mediates CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection

Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per millilite

Crystalline fibrillar gel formation in aqueous surfactant-antioxidant system

Cetyltrimethylammonium bromide (CTAB) is a well-known cationic surfactant capable to micellize into diverse morphologies in aqueous medium. We observed the formation of an opaque gel state from aqueous CTAB solution in the presence of the aromatic additive, para-coumaric acid (PCA). Optical microscopic images revealed the presence of large fibrils in the system at room temperature. Gel nature of the fibrils was confirmed by rheological measurements. Presence of interstitial water in the fibrils was recognized with Raman spectroscopy. On heating the sample above 30 ° C, the fibrillar gel state changes to a transparent liquid state with Newtonian flow properties. Dynamic light scattering study hinted the presence of small micelles in the solution above 30 ° C. Thus the system showed a temperature-dependent structural transition from opaque water-swollen gel to transparent micellar liquid. The formation of water-swollen fibrillar network is attributed to surfactant-additive intermolecular interactions in aqueous medium. Transition to micelle phase above 30 ° C is related to Kraft transition which is observed at significantly lower temperature for CTAB in the absence of PCA. The structural features of PCA play a key role in promoting fibrillar network formation and elevating the Kraft transition in aqueous solution of CTAB