In: Annual Review of Immunology
P. falciparum remains a serious public health problem and a continuous challenge for the immune system due to the complexity and diversity of the pathogen. Recent advances from several laboratories in the characterization of the antibody response to the parasite have led to the identification of critical targets for protection and revealed a new mechanism of diversification based on the...
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In: Current opinion in immunology, 2016, vol. 41, no. August, p. 62-67
In the last decade, progress in the analysis of the human immune response and in the isolation of human monoclonal antibodies have provided an innovative approach to the identification of protective antigens which are the basis for the design of vaccines capable of eliciting effective B-cell immunity. In this review we illustrate, with relevant examples, the power of this approach that can...
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In: Frontiers in immunology, 2017, vol. 8, p. 1563
Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable...
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In: EMBO molecular medicine, 2018, vol. 10, p. e8879
Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells...
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In: Cell, 2019, vol. 177, no. 6, p. 1420-1431.e17
Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein ...
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In: Cell reports, 2017, vol. 18, no. 10, p. 2427-2440
The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7)...
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In: Nature communications, 2016, vol. 7, p. 11541
CD4+ Th17 are heterogeneous in terms of cytokine production and capacity to initiate autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that experimental priming of encephalitogenic Th cells expressing RORγt and T-bet and producing IL-17A, IFN-γ and GM-CSF but not IL-10 (Th1/Th17), is dependent on the presence of pertussis toxin (PTX) at the...
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In: Nature communications, 2015, vol. 6, p. 7375
Pulmonary alveolar proteinosis (PAP) is a severe autoimmune disease caused by autoantibodies that neutralize GM-CSF resulting in impaired function of alveolar macrophages. In this study, we characterize 21 GM-CSF autoantibodies from PAP patients and find that somatic mutations critically determine their specificity for the self-antigen. Individual antibodies only partially neutralize GM-CSF...
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In: Nature communications, 2015, vol. 6, p. 6431
T helper (TH) cell polarization during priming is modulated by a number of signals, but whether polarization to a given phenotype also influences recall responses of memory TH cells is relatively unknown. Here we show that miR-181a is selectively induced in both human and mouse naive T cells differentiating into the TH17, but not TH1 or TH2 subset. In human memory TH17 cells, miR-181a...
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In: Plos one, 2013, vol. 8, no. 2, p. e55561
Antibodies play an increasing pivotal role in both basic research and the biopharmaceutical sector, therefore technology for characterizing and improving their properties through rational engineering is desirable. This is a difficult task thought to require high-resolution x-ray structures, which are not always available. We, instead, use a combination of solution NMR epitope mapping and ...
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