Normal human lymph node T follicular helper cells and germinal center B cells accessed via fine needle aspirations

Havenar-Daughton, Colin; Newton, Isabel G.; Zare, Somaye; Reiss, Samantha M.; Schwan, Brittany; Suh, Min Ji; Hasteh, Farnaz; Levi, G.; Crotty, Shane

doi:10.1016/j.jim.2020.112746

Cited by 35 publications

(23 citation statements)

References 20 publications

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“…or i.n. immunization with Ads in animal models, and these questions are even more difficult to address in humans, without the use of invasive procedures (such as fine needle aspirates of lymph nodes) (136).…”

Section: Route Of Administrationmentioning

confidence: 99%

Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines

2020

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Adenoviral vectors are a safe and potently immunogenic vaccine delivery platform. Non-replicating Ad vectors possess several attributes which make them attractive vaccines for infectious disease, including their capacity for high titer growth, ease of manipulation, safety, and immunogenicity in clinical studies, as well as their compatibility with clinical manufacturing and thermo-stabilization procedures. In general, Ad vectors are immunogenic vaccines, which elicit robust transgene antigen-specific cellular (namely CD8 + T cells) and/or humoral immune responses. A large number of adenoviruses isolated from humans and non-human primates, which have low seroprevalence in humans, have been vectorized and tested as vaccines in animal models and humans. However, a distinct hierarchy of immunological potency has been identified between diverse Ad vectors, which unfortunately limits the potential use of many vectors which have otherwise desirable manufacturing characteristics. The precise mechanistic factors which underlie the profound disparities in immunogenicity are not clearly defined and are the subject of ongoing, detailed investigation. It has been suggested that a combination of factors contribute to the potent immunogenicity of particular Ad vectors, including the magnitude and duration of vaccine antigen expression following immunization. Furthermore, the excessive induction of Type I interferons by some Ad vectors has been suggested to impair transgene expression levels, dampening subsequent immune responses. Therefore, the induction of balanced, but not excessive stimulation of innate signaling is optimal. Entry factor binding or receptor usage of distinct Ad vectors can also affect their in vivo tropism following administration by different routes. The abundance and accessibility of innate immune cells and/or antigen-presenting cells at the site of injection contributes to early innate immune responses to Ad vaccination, affecting the outcome of the adaptive immune response. Although a significant amount of information exists regarding the tropism determinants of the common human adenovirus type-5 vector, very little is known about the receptor usage and tropism of rare species or non-human Ad vectors. Increased understanding of how different facets of the host response to Ad vectors contribute to their immunological potency will be essential for the development of optimized and customized Ad vaccine platforms for specific diseases.

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Section: Route Of Administrationmentioning

confidence: 99%

Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines

2020

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“…B cells and plasma cells from the extrafollicular and GC reactions can enter the blood, which has been the most common source of these cells in human immunological studies. Relatively few studies of human immune responses have directly examined lymph nodes, spleen, or other potent organizing sites of adaptive immunity, although fine-needle aspiration of lymph node cells offers a strategy to address this limitation in the future ( Havenar-Daughton et al., 2020 ).…”

Section: B-lineage Cells In Sars-cov-2 Infectionmentioning

confidence: 99%

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Röltgen

Boyd

2021

Cell Host & Microbe

118

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Antibodies, and the B cell and plasma cell populations responsible for their production, are key components of the human immune system’s response to SARS-CoV-2, which has caused the coronavirus disease 2019 (COVID-19) pandemic. Here, we review findings addressing the nature of antibody responses against SARS-CoV-2 and their role in protecting from infection or modulating COVID-19 disease severity. In just over a year, much has been learned, and replicated in independent studies, about human immune responses to this pathogen, contributing to the development of effective vaccines. Nevertheless, important questions remain about the duration and effectiveness of antibody responses, differences between immunity derived from infection compared to vaccination, the cellular basis for serological findings, and the extent to which viral variants will escape from current immunity.

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“…It is currently unknown whether seasonal influenza virus immunization of humans can elicit a GC response in the draining lymph nodes (LN) where diversification and maturation of recruited B cells can occur. Studies examining human B cell responses have traditionally focused on sampling the easily accessible blood compartment, but ultrasound-guided fine needle aspiration (FNA) has enabled sampling of LNs with good representation of cell populations recovered by excisional biopsy, including GC B cells 7 – 9 .…”

Section: Introductionmentioning

confidence: 99%

Human germinal centres engage memory and naive B cells after influenza vaccination

Turner

Zhou

Han

et al. 2020

Nature

235

247

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Summary Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, leading to a transient wave of circulating antibody-secreting plasmablasts 1 – 3 . This recall response contributes to “original antigenic sin,” the selective boosting of antibody specificities from prior exposures to influenza virus antigens 4 . It remains unclear whether such vaccination can also induce germinal centre (GC) reactions in the draining lymph node (LN) where diversification and maturation of recruited B cells can occur 5 . Here we used ultrasound-guided fine needle aspiration to serially sample the draining LNs and investigate the dynamics and specificity of GC B cell responses after influenza vaccination in humans. We show that influenza vaccine-binding GC B cells can be detected as early as 1 week after vaccination. In 3 out of 8 participants, we detected vaccine-binding GC B cells up to 9 weeks after vaccination. Between 12% and 88% of the responding GC B cell clones overlapped with those detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation (SHM) and encoded broadly cross-reactive monoclonal antibodies (mAbs). In contrast, vaccine-induced B cell clones detected only in the GC compartment exhibited significantly lower SHM frequencies and predominantly encoded strain-specific mAbs, suggesting a naïve B cell origin. Electron microscopy-based epitope mapping revealed that some of these strain-specific mAbs recognized epitopes that were not targeted by the early plasmablast response. Our results indicate that influenza virus vaccination of humans can elicit a GC reaction to which B cell clones targeting novel epitopes are more likely to be recruited, thereby broadening the spectrum of vaccine-induced protective antibodies against this rapidly mutating pathogen.

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Normal human lymph node T follicular helper cells and germinal center B cells accessed via fine needle aspirations

Cited by 35 publications

References 20 publications

Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines

Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines

Antibody and B cell responses to SARS-CoV-2 infection and vaccination

Human germinal centres engage memory and naive B cells after influenza vaccination

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