Counts, J. | Search bioRxiv

bioRxiv2024

Synchronization of Human Circadian Genes Between in vivo and Cultured Blood Samples

Transcriptomic studies of human circadian rhythm are limited in efficacy by the invasiveness of sampling. Studies of circadian dynamics should ideally use multiple blood samples drawn at regular intervals over the course of a day. This is difficult to achieve, particularly at night, without disrupting the very circadian rhythm that is being studied. We propose a method by which blood is drawn at a single initial timepoint, then cultured and repeatedly sampled over the course of a day. This method is minimally invasive to the subject. Our results demonstrate that the expression levels of circadian genes are more closely correlated between the cultured (ex vivo) cells and live (in vivo) samples than non-circadian genes, suggesting that this method can be used for effective circadian analysis.

genomics↗

bioRxiv2023

Vaccine induction of CD4-mimicking broadly neutralizing antibody precursors in macaques

The CD4 binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that can be targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccines have not elicited CD4bs bnAbs for many reasons, including the CD4bs is occluded by glycans, immunogen expansion of appropriate naive B cells, and selection of functional antibody mutations. Here, we demonstrate immunization of macaques with a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structural and genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAbs bound to HIV-1 Env demonstrated binding angles similar to human bnAbs and heavy chain second complementarity determining region-dependent binding characteristic of all known human CD4-mimicking bnAbs. Macaque nAbs were derived from variable and joining gene segments orthologous to the genes of human VH1-46-class bnAbs. This vaccine study initiated the B cells from which derive CD4bs bnAbs in primates, accomplishing the key first step in development of an effective HIV-1 vaccine.

immunology↗