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Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Rebecca P. Payne, Stephanie Longet, James A. Austin, Donal T. Skelly, Wanwisa Dejnirattisai, Sandra Adele, Naomi Meardon, Sian Faustini, Saly Al-Taei, Shona C. Moore, Tom Tipton, Luisa M. Hering, Adrienn Angyal, Rebecca Brown, Alexander R. Nicols, Natalie Gillson, Susan L. Dobson, Ali Amini, Piyada Supasa, Andrew Cross, Alice Bridges-Webb, Laura Silva Reyes, Aline Linder, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Thomas Altmann, Hailey Hornsby, Rachel Whitham, Eloise Phillips, Tom Malone, Alexander Hargreaves, Adrian Shields, Ayoub Saei, Sarah Foulkes, Lizzie Stafford, Sile Johnson, Daniel G. Wootton, Christopher P. Conlon, Katie Jeffery, Philippa C. Matthews, John Frater, Alexandra S. Deeks, Andrew J. Pollard, Anthony Brown, Sarah L. Rowland-Jones, Juthathip Mongkolsapaya, Eleanor Barnes, Susan Hopkins, Victoria Hall, Christina Dold, Christopher JA. Duncan, Alex Richter, Miles Carroll, Gavin Screaton, Thushan I. de Silva, Lance Turtle, Paul Klenerman, Susanna Dunachie, PITCH Consortium,

Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK healthcare workers. The first vaccine dose induced protection from ... Read more >>

Cell (Cell)
[2021, :]

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Spatially confined sub-tumor microenvironments in pancreatic cancer.

Barbara T Grünwald, Antoine Devisme, Geoffroy Andrieux, Foram Vyas, Kazeera Aliar, Curtis W McCloskey, Andrew Macklin, Gun Ho Jang, Robert Denroche, Joan Miguel Romero, Prashant Bavi, Peter Bronsert, Faiyaz Notta, Grainne O'Kane, Julie Wilson, Jennifer Knox, Laura Tamblyn, Molly Udaskin, Nikolina Radulovich, Sandra E Fischer, Melanie Boerries, Steven Gallinger, Thomas Kislinger, Rama Khokha,

Intratumoral heterogeneity is a critical frontier in understanding how the tumor microenvironment (TME) propels malignant progression. Here, we deconvolute the human pancreatic TME through large-scale integration of histology-guided regional multiOMICs with clinical data and patient-derived preclinical models. We discover "subTMEs," histologically definable tissue states anchored in fibroblast plasticity, with regional ... Read more >>

Cell (Cell)
[2021, :]

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Microbiota regulates intratumoral monocytes to promote anti-tumor immune responses.

Kathy D McCoy, Markus B Geuking,

The gut microbiota has been shown to promote the efficacy of cancer therapy through regulating adaptive immune responses. In this issue of Cell, Lam et al. provide new evidence demonstrating that specific gut bacteria also reprogram the innate immune tumor microenvironment to enhance the efficacy of cancer therapies. ... Read more >>

Cell (Cell)
[2021, 184(21):5301-5303]

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Mechanoreceptor synapses in the brainstem shape the central representation of touch.

Brendan P Lehnert, Celine Santiago, Erica L Huey, Alan J Emanuel, Sophia Renauld, Nusrat Africawala, Ilayda Alkislar, Yang Zheng, Ling Bai, Charalampia Koutsioumpa, Jennifer T Hong, Alexandra R Magee, Christopher D Harvey, David D Ginty,

Mammals use glabrous (hairless) skin of their hands and feet to navigate and manipulate their environment. Cortical maps of the body surface across species contain disproportionately large numbers of neurons dedicated to glabrous skin sensation, in part reflecting a higher density of mechanoreceptors that innervate these skin regions. Here, we ... Read more >>

Cell (Cell)
[2021, :]

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Enhanced prime editing systems by manipulating cellular determinants of editing outcomes.

Peter J Chen, Jeffrey A Hussmann, Jun Yan, Friederike Knipping, Purnima Ravisankar, Pin-Fang Chen, Cidi Chen, James W Nelson, Gregory A Newby, Mustafa Sahin, Mark J Osborn, Jonathan S Weissman, Britt Adamson, David R Liu,

While prime editing enables precise sequence changes in DNA, cellular determinants of prime editing remain poorly understood. Using pooled CRISPRi screens, we discovered that DNA mismatch repair (MMR) impedes prime editing and promotes undesired indel byproducts. We developed PE4 and PE5 prime editing systems in which transient expression of an ... Read more >>

Cell (Cell)
[2021, :]

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cAAVe phaenomena: Beware of appearances!

Filippo Calzolari, Benedikt Berninger,

In this issue of Cell, Wang et al. come to the unsettling conclusion that adeno-associated viruses, despite being engineered for glia-specific expression, can become widely active in endogenous neurons, misleading researchers in their quest for efficient conversion of glia into neurons for brain repair. ... Read more >>

Cell (Cell)
[2021, 184(21):5303-5305]

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Cohesin mediates DNA loop extrusion by a "swing and clamp" mechanism.

Benedikt W Bauer, Iain F Davidson, Daniel Canena, Gordana Wutz, Wen Tang, Gabriele Litos, Sabrina Horn, Peter Hinterdorfer, Jan-Michael Peters,

Structural maintenance of chromosomes (SMC) complexes organize genome topology in all kingdoms of life and have been proposed to perform this function by DNA loop extrusion. How this process works is unknown. Here, we have analyzed how loop extrusion is mediated by human cohesin-NIPBL complexes, which enable chromatin folding in ... Read more >>

Cell (Cell)
[2021, 184(21):5448-5464.e22]

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A mouse-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for development.

Andrew J Modzelewski, Wanqing Shao, Jingqi Chen, Angus Lee, Xin Qi, Mackenzie Noon, Kristy Tjokro, Gabriele Sales, Anne Biton, Aparna Anand, Terence P Speed, Zhenyu Xuan, Ting Wang, Davide Risso, Lin He,

Retrotransposons mediate gene regulation in important developmental and pathological processes. Here, we characterized the transient retrotransposon induction during preimplantation development of eight mammals. Induced retrotransposons exhibit similar preimplantation profiles across species, conferring gene regulatory activities, particularly through long terminal repeat (LTR) retrotransposon promoters. A mouse-specific MT2B2 retrotransposon promoter generates an ... Read more >>

Cell (Cell)
[2021, :]

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Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.

Khiem C Lam, Romina E Araya, April Huang, Quanyi Chen, Martina Di Modica, Richard R Rodrigues, Amélie Lopès, Sarah B Johnson, Benjamin Schwarz, Eric Bohrnsen, Alexandria P Cogdill, Catharine M Bosio, Jennifer A Wargo, Maxwell P Lee, Romina S Goldszmid,

The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME ... Read more >>

Cell (Cell)
[2021, 184(21):5338-5356.e21]

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Atlas of clinically distinct cell states and ecosystems across human solid tumors.

Bogdan A Luca, Chloé B Steen, Magdalena Matusiak, Armon Azizi, Sushama Varma, Chunfang Zhu, Joanna Przybyl, Almudena Espín-Pérez, Maximilian Diehn, Ash A Alizadeh, Matt van de Rijn, Andrew J Gentles, Aaron M Newman,

Determining how cells vary with their local signaling environment and organize into distinct cellular communities is critical for understanding processes as diverse as development, aging, and cancer. Here we introduce EcoTyper, a machine learning framework for large-scale identification and validation of cell states and multicellular communities from bulk, single-cell, and ... Read more >>

Cell (Cell)
[2021, 184(21):5482-5496.e28]

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A phosphate starvation response-centered network regulates mycorrhizal symbiosis.

Jincai Shi, Boyu Zhao, Shuang Zheng, Xiaowei Zhang, Xiaolin Wang, Wentao Dong, Qiujin Xie, Gang Wang, Yunping Xiao, Fan Chen, Nan Yu, Ertao Wang,

To secure phosphorus (P) from soil, most land plants use a direct phosphate uptake pathway via root hairs and epidermis and an indirect phosphate uptake pathway via mycorrhizal symbiosis. The interaction between these two pathways is unclear. Here, we mapped a network between transcription factors and mycorrhizal symbiosis-related genes using ... Read more >>

Cell (Cell)
[2021, :]

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A selective antibiotic for Lyme disease.

Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E McCarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis,

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a ... Read more >>

Cell (Cell)
[2021, 184(21):5405-5418.e16]

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In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target.

Xiaoqing Wang, Collin Tokheim, Shengqing Stan Gu, Binbin Wang, Qin Tang, Yihao Li, Nicole Traugh, Zexian Zeng, Yi Zhang, Ziyi Li, Boning Zhang, Jingxin Fu, Tengfei Xiao, Wei Li, Clifford A Meyer, Jun Chu, Peng Jiang, Paloma Cejas, Klothilda Lim, Henry Long, Myles Brown, X Shirley Liu,

Despite remarkable clinical efficacy of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits for triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that deletion of the E3 ubiquitin ligase Cop1 in cancer cells decreases secretion of macrophage-associated ... Read more >>

Cell (Cell)
[2021, 184(21):5357-5374.e22]

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Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.

Nitzan Tal, Benjamin R Morehouse, Adi Millman, Avigail Stokar-Avihail, Carmel Avraham, Taya Fedorenko, Erez Yirmiya, Ehud Herbst, Alexander Brandis, Tevie Mehlman, Yaara Oppenheimer-Shaanan, Alexander F A Keszei, Sichen Shao, Gil Amitai, Philip J Kranzusch, Rotem Sorek,

The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, ... Read more >>

Cell (Cell)
[2021, :]

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Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.

Golnaz Morad, Beth A Helmink, Padmanee Sharma, Jennifer A Wargo,

Unprecedented advances have been made in cancer treatment with the use of immune checkpoint blockade (ICB). However, responses are limited to a subset of patients, and immune-related adverse events (irAEs) can be problematic, requiring treatment discontinuation. Iterative insights into factors intrinsic and extrinsic to the host that impact ICB response ... Read more >>

Cell (Cell)
[2021, 184(21):5309-5337]

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From microbial membrane proteins to the mysteries of emotion.

Karl Deisseroth,

On the occasion of the 2021 Lasker Basic Medical Research Award to Karl Deisseroth, Peter Hegemann, and Dieter Oesterhelt (for "the discovery of light-sensitive microbial proteins that can activate or deactivate individual brain cells-leading to the development of optogenetics and revolutionizing neuroscience"), Deisseroth reflects on this international collaboration, his basic ... Read more >>

Cell (Cell)
[2021, 184(21):5279-5285]

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RetroCHMP3 blocks budding of enveloped viruses without blocking cytokinesis.

Lara Rheinemann, Diane Miller Downhour, Kate Bredbenner, Gaelle Mercenne, Kristen A Davenport, Phuong Tieu Schmitt, Christina R Necessary, John McCullough, Anthony P Schmitt, Sanford M Simon, Wesley I Sundquist, Nels C Elde,

Many enveloped viruses require the endosomal sorting complexes required for transport (ESCRT) pathway to exit infected cells. This highly conserved pathway mediates essential cellular membrane fission events, which restricts the acquisition of adaptive mutations to counteract viral co-option. Here, we describe duplicated and truncated copies of the ESCRT-III factor CHMP3 ... Read more >>

Cell (Cell)
[2021, 184(21):5419-5431.e16]

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Bombesin-like peptide recruits disinhibitory cortical circuits and enhances fear memories.

Sarah Melzer, Elena R Newmark, Grace Or Mizuno, Minsuk Hyun, Adrienne C Philson, Eleonora Quiroli, Beatrice Righetti, Malika R Gregory, Kee Wui Huang, James Levasseur, Lin Tian, Bernardo L Sabatini,

Disinhibitory neurons throughout the mammalian cortex are powerful enhancers of circuit excitability and plasticity. The differential expression of neuropeptide receptors in disinhibitory, inhibitory, and excitatory neurons suggests that each circuit motif may be controlled by distinct neuropeptidergic systems. Here, we reveal that a bombesin-like neuropeptide, gastrin-releasing peptide (GRP), recruits disinhibitory ... Read more >>

Cell (Cell)
[2021, :]

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Cellular bases of olfactory circuit assembly revealed by systematic time-lapse imaging.

Tongchao Li, Tian-Ming Fu, Kenneth Kin Lam Wong, Hongjie Li, Qijing Xie, David J Luginbuhl, Mark J Wagner, Eric Betzig, Liqun Luo,

Neural circuit assembly features simultaneous targeting of numerous neuronal processes from constituent neuron types, yet the dynamics is poorly understood. Here, we use the Drosophila olfactory circuit to investigate dynamic cellular processes by which olfactory receptor neurons (ORNs) target axons precisely to specific glomeruli in the ipsi- and contralateral antennal ... Read more >>

Cell (Cell)
[2021, 184(20):5107-5121.e14]

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Revisiting astrocyte to neuron conversion with lineage tracing in vivo.

Lei-Lei Wang, Carolina Serrano, Xiaoling Zhong, Shuaipeng Ma, Yuhua Zou, Chun-Li Zhang,

In vivo cell fate conversions have emerged as potential regeneration-based therapeutics for injury and disease. Recent studies reported that ectopic expression or knockdown of certain factors can convert resident astrocytes into functional neurons with high efficiency, region specificity, and precise connectivity. However, using stringent lineage tracing in the mouse brain, we ... Read more >>

Cell (Cell)
[2021, 184(21):5465-5481.e16]

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Building and supporting identity in peer review.

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Cell (Cell)
[2021, 184(20):5071-5072]

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Deciphering the cancer microenvironment from bulk data with EcoTyper.

Andrea Rolong, Bob Chen, Ken S Lau,

In this issue of Cell, Luca, Steen et al. develop the EcoTyper software to deconvolve tumor-microenvironment interactions from high volume bulk transcriptomics data. They demonstrate its effectiveness in improving predictions for tumor progression and patient prognosis for a variety of tumor types from multiple data sources. ... Read more >>

Cell (Cell)
[2021, 184(21):5306-5308]

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Persistent progress.

The highly effective and safe mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines draw on decades of painstaking research to overcome the many hurdles for delivering, expressing, and avoiding toxicity of therapeutic mRNA. Cell editor Nicole Neuman talked with Dr. Katalin Karikó and Dr. Drew Weissman, recipients of the ... Read more >>

Cell (Cell)
[2021, 184(21):5293-5296]

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How the discovery of microbial opsins led to the development of optogenetics.

Jeffrey M Friedman,

This year's Lasker Award recognizes Dieter Oesterhelt, Peter Hegemann, and Karl Deisseroth for their discovery of microbial opsins as light-activated ion conductors and the development of optogenetics using these proteins to regulate neural activity in awake, behaving animals. Optogenetics has revolutionized neuroscience and transformed our understanding of brain function. ... Read more >>

Cell (Cell)
[2021, 184(21):5266-5270]

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Ca2+ sensor-mediated ROS scavenging suppresses rice immunity and is exploited by a fungal effector.

Mingjun Gao, Yang He, Xin Yin, Xiangbin Zhong, Bingxiao Yan, Yue Wu, Jin Chen, Xiaoyuan Li, Keran Zhai, Yifeng Huang, Xiangyu Gong, Huizhong Chang, Shenghan Xie, Jiyun Liu, Jiaxing Yue, Jianlong Xu, Guiquan Zhang, Yiwen Deng, Ertao Wang, Didier Tharreau, Guo-Liang Wang, Weibing Yang, Zuhua He,

Plant immunity is activated upon pathogen perception and often affects growth and yield when it is constitutively active. How plants fine-tune immune homeostasis in their natural habitats remains elusive. Here, we discover a conserved immune suppression network in cereals that orchestrates immune homeostasis, centering on a Ca<sup>2+</sup>-sensor, RESISTANCE OF RICE ... Read more >>

Cell (Cell)
[2021, 184(21):5391-5404.e17]

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