Antibiotic-resistant bacteria are a major global health threat that continues to rise due to a lack of effective vaccines. Of concern are Klebsiella pneumoniae (K. pneumoniae) that fail to induce in vivo germinal center B cell responses, which facilitate antibody production to fight infection. Immunotherapies using antibodies targeting antibiotic-resistant bacteria are emerging as promising alternatives, however, they cannot be efficiently derived ex vivo, necessitating the need for immune technologies to develop therapeutics. Here, polyethylene glycol (PEG)-based immune organoids are developed to elucidate the effects of polymer end-point chemistry, integrin ligands, and mode of K. pneumoniae antigen presentation on germinal center-like B cell phenotype and epigenetics, to better define the lymph node microenvironment factors regulating ex vivo germinal center dynamics. Notably, PEG vinyl sulfone or acrylate fail to sustain primary immune cells, but functionalization with maleimide (PEG-4MAL) leads to B cell expansion and germinal center-like induction. RNA sequencing analysis of lymph node stromal and germinal center B cells shows niche associated heterogeneity of integrin-related genes. Incorporation of niche-mimicking peptides reveals that collagen-1 promotes germinal center-like dynamics and epigenetics. PEG-4MAL organoids elucidate the impact of K. pneumoniae outer membrane-embedded protein antigen versus soluble antigen presentation on germinal centers and preserve the response across young and aged mice.

Chronic hepatitis B affects more than a million people in the U.S. and causes 4,000 deaths each year, yet the costs and benefits of treatment have not been fully evaluated. Using a model that simulates disease progression, we compare treatment programs for hepatitis B that start at an early versus late stage of disease. Early care is shown to improve health, reduce premature deaths, and prevent expensive complications, making it highly cost-effective. Our results demonstrate the importance of linking hepatitis B screening to treatment, and illustrate how predictive models can be used to evaluate strategies for improving access to care.

We report the discovery of TgPRELID, a previously uncharacterized mitochondrial protein linked to multidrug resistance in the parasite Toxoplasma gondii. Drug resistance remains a major problem in the battle against parasitic infection, and understanding how TgPRELID mutations augment resistance to multiple, distinct compounds will reveal needed insights into the development of new therapies for toxoplasmosis and other related parasitic diseases.

Memory B cells originate in response to antigenic stimulation in B‐cell follicles of secondary lymphoid organs where naive B cells undergo maturation within a subanatomical microenvironment, the germinal centers. The understanding of memory B‐cell immunology and its regulation is based primarily on sophisticated experiments that involve mouse models. To date, limited evidence exists on whether memory B cells can be successfully engineered ex vivo, specifically using biomaterials‐based platforms that support the growth and differentiation of B cells. Here, we report the characterization of a recently reported maleimide‐functionalized poly(ethylene glycol) (PEG) hydrogels as immune organoids towards the development of early memory B‐cell phenotype and germinal center‐like B cells. We demonstrate that the use of interleukin 9 (IL9), IL21, and bacterial antigen presentation as outer membrane‐bound fragments drives the conversion of naive, primary murine B cells to early memory phenotype in ex vivo immune organoids. These findings describe the induction of early memory B‐cell‐like phenotype in immune organoids and highlight the potential of synthetic organoids as a platform for the future development of antigen‐specific bona fide memory B cells for the study of the immune system and generation of therapeutic antibodies.

Antibiotic-resistant bacteria are a major global health threat that continues to rise due to a lack of effective vaccines. Of concern are Klebsiella pneumoniae that fail to induce in vivo germinal center B cell responses, which facilitate antibody production to fight infection. Immunotherapies using antibodies targeting antibiotic-resistant bacteria are emerging as promising alternatives, however, cannot be efficiently derived ex vivo, necessitating the need for immune technologies to develop therapeutics. Here, four-arm PEG-organoids were developed to elucidate the effects of polymer endpoint chemistry, integrin ligands, and mode of K. pneumoniae antigen presentation on germinal centerlike B cell epigenetics, to better define the cell-microenvironment factors regulating ex vivo germinal center dynamics. Notably, PEG vinyl sulfone or acrylate failed to sustain primary immune cells, but functionalization with maleimide (PEG-4MAL) led to B cell expansion and germinal center-like induction. RNA sequencing analysis of lymph node stromal and germinal center B cells showed niche associated heterogeneity of integrin-related genes. Incorporation of niche-mimicking bioadhesive peptides revealed that collagen 1 mimicking peptides promoted germinal center-like dynamics and epigenetics. PEG-4MAL organoids elucidated the impact of K. pneumoniae membrane embedded protein antigen versus soluble antigen presentation on germinal center-like activation and preserved the response across young and aged mice.