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Article ; Online: Immune responses to SARS-CoV-2 in the lung.

Arunachalam, Prabhu S

2021 Volume 76, Issue 10, Page(s) 961

MeSH term(s)	COVID-19 ; Humans ; Immunity, Innate ; Lung ; SARS-CoV-2
Language	English
Publishing date	2021-06-04
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2021-217231
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Article ; Online: Emerging concepts in the science of vaccine adjuvants.

Pulendran, Bali / S Arunachalam, Prabhu / O'Hagan, Derek T

Nature reviews. Drug discovery

2021 Volume 20, Issue 6, Page(s) 454–475

Abstract: Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further ... ...

Abstract	Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. However, a revolution in our understanding of the activation of the innate immune system through pattern recognition receptors (PRRs) is improving the mechanistic understanding of adjuvants, and recent conceptual advances highlight the notion that tissue damage, different forms of cell death, and metabolic and nutrient sensors can all modulate the innate immune system to activate adaptive immunity. Furthermore, recent advances in the use of systems biology to probe the molecular networks driving immune response to vaccines ('systems vaccinology') are revealing mechanistic insights and providing a new paradigm for the vaccine discovery and development process. Here, we review the 'known knowns' and 'known unknowns' of adjuvants, discuss these emerging concepts and highlight how our expanding knowledge about innate immunity and systems vaccinology are revitalizing the science and development of novel adjuvants for use in vaccines against COVID-19 and future pandemics.
MeSH term(s)	Adjuvants, Immunologic/pharmacology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/pharmacology ; Drug Development ; Humans ; Immunity, Innate/drug effects ; SARS-CoV-2 ; Vaccinology/methods ; Vaccinology/trends
Chemical Substances	Adjuvants, Immunologic ; COVID-19 Vaccines
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-021-00163-y
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Article ; Online: A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice.

Lee, Audrey / Scott, Madeleine K D / Wimmers, Florian / Arunachalam, Prabhu S / Luo, Wei / Fox, Christopher B / Tomai, Mark / Khatri, Purvesh / Pulendran, Bali

Nature communications

2022 Volume 13, Issue 1, Page(s) 549

Abstract: Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being ... ...

Abstract	Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being evaluated in human clinical trials. However, the innate mechanisms of 3M-052 have not been fully characterized. Here, we perform flow cytometry, single cell RNA-seq and ATAC-seq to profile the kinetics, transcriptomics and epigenomics of innate immune cells in murine draining lymph nodes following 3M-052-Alum/Ovalbumin immunization. We find that 3M-052-Alum/OVA induces a robust antiviral and interferon gene program, similar to the yellow fever vaccine, which is known to confer long-lasting protection. Activation of myeloid cells in dLNs persists through day 28 and single cell analysis reveals putative TF-gene regulatory programs in distinct myeloid cells and heterogeneity of monocytes. This study provides a comprehensive characterization of the transcriptomics and epigenomics of innate populations in the dLNs after vaccination.
MeSH term(s)	Adaptive Immunity ; Adjuvants, Immunologic/chemistry ; Adjuvants, Immunologic/pharmacology ; Alum Compounds ; Animals ; Antibodies, Viral/immunology ; Epigenomics ; Female ; Humans ; Immunity, Humoral/immunology ; Immunity, Innate/drug effects ; Immunization ; Membrane Glycoproteins/agonists ; Mice ; Mice, Inbred C57BL ; Monocytes ; Myeloid Cells ; Ovalbumin ; Toll-Like Receptor 7/agonists ; Toll-Like Receptor 8/agonists ; Vaccination ; Vaccines, Attenuated/immunology
Chemical Substances	Adjuvants, Immunologic ; Alum Compounds ; Antibodies, Viral ; Membrane Glycoproteins ; TLR7 protein, human ; TLR8 protein, human ; TLR8 protein, mouse ; Tlr7 protein, mouse ; Toll-Like Receptor 7 ; Toll-Like Receptor 8 ; Vaccines, Attenuated ; ovalbumin-alum ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2022-01-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28197-9
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Article ; Online: AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans.

Science immunology

2024 Volume 9, Issue 94, Page(s) eadi8039

Abstract: Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive ... ...

Abstract	Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4
MeSH term(s)	Adult ; Humans ; Influenza Vaccines ; Memory B Cells ; COVID-19 Vaccines ; Influenza, Human ; Antibodies, Viral ; COVID-19/prevention & control ; Drug Combinations ; Polysorbates ; Squalene ; alpha-Tocopherol
Chemical Substances	AS03 adjuvant (A7YT618XBV) ; Influenza Vaccines ; COVID-19 Vaccines ; Antibodies, Viral ; Drug Combinations ; Polysorbates ; Squalene (7QWM220FJH) ; alpha-Tocopherol (H4N855PNZ1)
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adi8039
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Article ; Online: Author Correction: A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

Nature communications

2023 Volume 14, Issue 1, Page(s) 6211

Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Published Erratum
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42061-4
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Article ; Online: Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus.

JCI insight

2024 Volume 9, Issue 5

Abstract: Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive ... ...

Abstract	Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.
MeSH term(s)	Humans ; BNT162 Vaccine ; COVID-19 Vaccines ; SARS-CoV-2 ; COVID-19/prevention & control ; Lupus Erythematosus, Systemic ; Vaccination
Chemical Substances	BNT162 Vaccine ; COVID-19 Vaccines
Language	English
Publishing date	2024-03-08
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.176556
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Article ; Online: A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice

Audrey Lee / Madeleine K. D. Scott / Florian Wimmers / Prabhu S. Arunachalam / Wei Luo / Christopher B. Fox / Mark Tomai / Purvesh Khatri / Bali Pulendran

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 13

Abstract: Adjuvants provide additional impetus for the immune response to vaccination regimens, however their modes of activity and impact on particular compartments of the immune response are currently not well understood. Here the authors perform high resolution ...

Abstract	Adjuvants provide additional impetus for the immune response to vaccination regimens, however their modes of activity and impact on particular compartments of the immune response are currently not well understood. Here the authors perform high resolution assessment of the immune response to a well-established vaccination model and show innate immune transcriptomic and epigenomic alterations of innate cells in the lymph nodes following vaccination.
Keywords	Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

Nature communications

2023 Volume 14, Issue 1, Page(s) 2149

Abstract: While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe ... ...

Abstract	While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1. Following a booster ~one year after the initial immunization, DCFHP-alum elicits a robust anamnestic response. To enable global accessibility, we generated a cell line that can enable production of thousands of vaccine doses per liter of cell culture and show that DCFHP-alum maintains potency for at least 14 days at temperatures exceeding standard room temperature. DCFHP-alum has potential as a once-yearly (or less frequent) booster vaccine, and as a primary vaccine for pediatric use including in infants.
MeSH term(s)	Animals ; Humans ; COVID-19 Vaccines ; Ferritins ; COVID-19/prevention & control ; SARS-CoV-2 ; Geranium ; Immune Sera ; Nanoparticles ; Primates ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; aluminum sulfate (34S289N54E) ; Ferritins (9007-73-2) ; Immune Sera ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37417-9
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Article ; Online: BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance.

Nature immunology

2023 Volume 25, Issue 1, Page(s) 41–53

Abstract: Bacille Calmette-Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or ... ...

Abstract	Bacille Calmette-Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted ∼3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (T
MeSH term(s)	Animals ; Mice ; Humans ; BCG Vaccine ; Feedback ; Adaptive Immunity ; Vaccination ; Weight Loss ; Antiviral Agents ; Immunity, Innate
Chemical Substances	BCG Vaccine ; Antiviral Agents
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01700-0
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Durability of immune responses to mRNA booster vaccination against COVID-19.

The Journal of clinical investigation

2023 Volume 133, Issue 10

Abstract: BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the ... ...

Abstract	BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.ResultsThe booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.
MeSH term(s)	Adult ; Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; COVID-19 Vaccines ; Vaccination ; RNA, Messenger ; Immunity ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI167955
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