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1.
Nat Immunol ; 24(6): 941-954, 2023 06.
Article in English | MEDLINE | ID: mdl-37095378

ABSTRACT

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Antibodies, Viral , COVID-19/prevention & control , SARS-CoV-2 , T-Lymphocytes , Immunogenicity, Vaccine
2.
Blood Adv ; 3(7): 1129-1144, 2019 04 09.
Article in English | MEDLINE | ID: mdl-30952679

ABSTRACT

Infectious mononucleosis, caused by infection with the human gamma-herpesvirus Epstein-Barr virus (EBV), manifests with one of the strongest CD8+ T-cell responses described in humans. The resulting T-cell memory response controls EBV infection asymptomatically in the vast majority of persistently infected individuals. Whether and how dendritic cells (DCs) contribute to the priming of this near-perfect immune control remains unclear. Here we show that of all the human DC subsets, plasmacytoid DCs (pDCs) play a central role in the detection of EBV infection in vitro and in mice with reconstituted human immune system components. pDCs respond to EBV by producing the interferon (IFN) subtypes α1, α2, α5, α7, α14, and α17. However, the virus curtails this type I IFN production with its latent EBV gene products EBNA3A and EBNA3C. The induced type I IFNs inhibit EBV entry and the proliferation of latently EBV-transformed B cells but do not influence lytic reactivation of the virus in vitro. In vivo, exogenous IFN-α14 and IFN-α17, as well as pDC expansion, delay EBV infection and the resulting CD8+ T-cell expansion, but pDC depletion does not significantly influence EBV infection. Thus, consistent with the observation that primary immunodeficiencies compromising type I IFN responses affect only alpha- and beta-herpesvirus infections, we found that EBV elicits pDC responses that transiently suppress viral replication and attenuate CD8+ T-cell expansion but are not required to control primary infection.


Subject(s)
Dendritic Cells/immunology , Epstein-Barr Virus Infections/immunology , Interferon Type I/biosynthesis , Animals , CD8-Positive T-Lymphocytes/pathology , Cell Proliferation , Humans , Interferon Type I/pharmacology , Mice , Virus Internalization/drug effects , Virus Replication
3.
J Cell Biol ; 203(5): 757-66, 2013 Dec 09.
Article in English | MEDLINE | ID: mdl-24322427

ABSTRACT

Antigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Antigen Presentation , Autophagy/physiology , Histocompatibility Antigens Class II/metabolism , Microfilament Proteins/metabolism , Phagosomes/metabolism , Autophagy-Related Protein 8 Family , Humans , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/physiology , NADPH Oxidase 2 , NADPH Oxidases/metabolism , NADPH Oxidases/physiology , Phagosomes/physiology , Reactive Oxygen Species/metabolism
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