Structural and antigenic characterization of novel and diverse glycoproteins.

(HNVs), a genus within the family, includes the highly virulent Nipah and Hendra viruses that cause yearly reoccurring outbreaks of deadly disease. Recent discoveries of several new species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized. Here, to explore the limits of structural and antigenic variation in HNVs, we construct an expanded, antigenically diverse panel of HNV fusion (F) and attachment (G) glycoproteins from 56 unique HNV strains that better reflects global HNV diversity.

Anti-HIV-1 B cell antigen receptor signaling and structure.

Unlabelled: The B cell antigen receptor (BCR) complex, comprised of antigen recognition and signaling components, functions in initiating B cell activation. While structural studies have described BCR domain organization, gaps remain in our understanding of its antigen binding domain (Fab, fragment antigen-binding) disposition, and how antigen binding is sensed to initiate signaling. Here, we report antigen affinity and signaling of the immunoglobulin (Ig) class IgM and IgG BCRs and define conformational states of full-length BCRs of two human broadly neutralizing antibodies, the glycan-specific, heavy chain domain-swapped, I-shaped 2G12, and a canonical Y-shaped antibody, CH31, that recognizes the CD4-binding site on the HIV-1 Envelope protein (Env).

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. Here, to precisely engineer bnAb boosting immunogens, we use molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env).

Safety and implementation of a phase 1 randomized GLA-SE-adjuvanted CH505TF gp120 HIV vaccine trial in newborns.

Background: The neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs) and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a novel glucopyranosyl lipid A (GLA)-stable emulsion (SE) adjuvant admixed with a first-in-infant CH505 transmitter-founder (CH505TF) gp120 immunogen designed to induce precursors for bnAbs against HIV.

Methods: HVTN 135 is a phase I randomized, placebo-controlled trial of CH505TF+GLA-SE or placebo.

Attention focused on memory: The episodic flanker effect with letters, words, colors, and pictures.

We report 10 experiments exploring the proposition that memory retrieval is perceptual attention turned inward. The experiments adapt the Eriksen and Eriksen perceptual flanker effect to a memory task in which subjects must decide whether a cued item in a probe display appeared in the same position in a memory list. Previous research with this episodic flanker task found distance and compatibility effects like those in the perceptual flanker task, suggesting that the same attentional spotlight is turned inward in memory retrieval.