Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination

Pejoski, David; Rham, Casimir de; Martinez-Murillo, Paola; Santoro, Francesco; Auderset, Floriane; Medaglini, Donata; Pozzi, Gianni; Vono, Maria; Lambert, Paul‐Henri; Huttner, Angela; Haks, Mariëlle C.; Ottenhoff, Tom H. M.; Villard, Jean; Siegrist, Claire‐Anne

doi:10.1038/s41541-020-0179-4

Cited by 18 publications

(14 citation statements)

References 19 publications

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“…Activation and proliferation of CD56 bright NK cells has previously been reported as a feature of whole organism or live-attenuated vaccines 24 – 29 , and is line with our previous observations with this vectored vaccine including secretion of NK cell activating cytokines in supernatants of EBOV GP stimulated PBMC 13 . Recent studies, published in this journal, demonstrate dose-dependent increases in NK cell numbers and functional modulation within days of live attenuated rVSV-ZEBOV vectored vaccination 30 . The longer-term effects observed here are consistent with the rapid proliferation and relatively long lifespan of CD56 bright NK cells 31 .…”

Section: Discussionmentioning

confidence: 92%

Durable natural killer cell responses after heterologous two-dose Ebola vaccination

et al. 2021

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Natural killer (NK) cells are implicated among immune effectors after vaccination against viral pathogens, including Ebola virus. The two-dose heterologous Ebola virus vaccine regimen, adenovirus type 26.ZEBOV followed by modified vaccinia Ankara-BN-Filo (EBOVAC2 consortium, EU Innovative Medicines Initiative), induces NK cell activation and anti-Ebola glycoprotein (GP) antibody-dependent NK cell activation post-dose 1, which is further elevated post-dose 2. Here, in a multicentre, phase 2 clinical trial (EBL2001), we demonstrate durable ex vivo NK cell activation 180 days after dose 2, with responses enriched in CD56bright NK cells. In vitro antibody-dependent responses to immobilised Ebola GP increased after dose 1, and remained elevated compared to pre-vaccination levels in serum collected 180 days later. Peak NK cell responses were observed post-dose 2 and NK cell IFN-γ responses remained significantly elevated at 180 days post-dose 2. Individual variation in NK cell responses were influenced by both anti-Ebola GP antibody concentrations and intrinsic interindividual differences in NK cell functional capacity. In summary, this study demonstrates durable NK cell responses after Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccination and could inform the immunological evaluation of future iterations of the vaccine regimen and vaccination schedules.

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Section: Discussionmentioning

confidence: 92%

Durable natural killer cell responses after heterologous two-dose Ebola vaccination

et al. 2021

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“…Yellow fever vaccine 17D induces proliferation and expansion of less differentiated CD56 bright and CD56 dim CD57 − NK cells; these cells also demonstrate enhanced responsiveness to in vitro restimulation with innate cytokines 92 . Similarly, increased absolute numbers of CD56 bright and CD56 dim NK cells are observed within 3 days of immunisation with the rVSV‐ZEBOV Ebola virus vaccine; increased NK cell expression of CXCR6 is an independent correlate of rVSV‐ZEBOV vaccine responsiveness whilst reduced frequencies of NKG2D + and increased frequencies of NKp30 and KIR + NK cells are inversely correlated with plasma cytokine and chemokine concentrations, indicating likely recirculation of NK cell subsets within 72 h of vaccination 93 . The Ad26.ZEBOV Ebola virus vaccine also activates CD56 bright NK cells as assessed by the induction of CD25 and Ki67 expression up to 14 days after the second dose 70 .…”

Section: Vaccination and Nk Cellsmentioning

confidence: 93%

“…92 Similarly, increased absolute numbers of CD56 bright and CD56 dim NK cells are observed within 3 days of immunisation with the rVSV-ZEBOV Ebola virus vaccine; increased NK cell expression of CXCR6 is an independent correlate of rVSV-ZEBOV vaccine responsiveness whilst reduced frequencies of NKG2D + and increased frequencies of NKp30 and KIR + NK cells are inversely correlated with plasma cytokine and chemokine concentrations, indicating likely recirculation of NK cell subsets within 72 h of vaccination. 93 The Ad26.ZEBOV Ebola virus vaccine also activates CD56 bright NK cells as assessed by the induction of CD25 and Ki67 expression up to 14 days after the second dose. 70 The extent to which different vaccine vectors, delivery platforms and adjuvating systems impact on NK cell differentiation will likely depend on their primary cellular tropism, interactions with pattern recognition receptors and downstream production of NK cell-activating cytokines; this aspect of vaccination has as yet received very little attention.…”

Section: Vaccination and Nk Cellsmentioning

confidence: 99%

Regulation of the human NK cell compartment by pathogens and vaccines

Goodier

Riley

2021

Clin & Trans Imm

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Natural killer cells constitute a phenotypically diverse population of innate lymphoid cells with a broad functional spectrum. Classically defined as cytotoxic lymphocytes with the capacity to eliminate cells lacking self-MHC or expressing markers of stress or neoplastic transformation, critical roles for NK cells in immunity to infection in the regulation of immune responses and as vaccineinduced effector cells have also emerged. A crucial feature of NK cell biology is their capacity to integrate signals from pathogen-, tumor-or stress-induced innate pathways and from antigenspecific immune responses. The extent to which innate and acquired immune mediators influence NK cell effector function is influenced by the maturation and differentiation state of the NK cell compartment; moreover, NK cell differentiation is driven in part by exposure to infection. Pathogens can thus mould the NK cell response to maximise their own success and/or minimise the damage they cause. Here, we review recent evidence that pathogen-and vaccine-derived signals influence the differentiation, adaptation and subsequent effector function of human NK cells.

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“…Recently, NK cells were suggested to contribute to the early protective response of the Ebolavirus vaccine rVSV-ZEBOV [125]. System vaccinology studies identified the post-vaccination phenotype of NK cells to be positively correlated with antigen-specific responses induced by the vaccine on day 28 [126].…”

Section: Nk Cells In Hcmv Vaccinationmentioning

confidence: 99%

“…NK responses have been reported in vaccines employing live attenuated virus [131,132] viral vectors [125] and non-infectious virus-like particles [133]. All three strategies have in common the provision of a number of PAMPs that are strong activators of pattern recognition receptors (PRRs) present in immune cells.…”

Section: Induction Of Nk Cell Memorymentioning

confidence: 99%

NK Cell Memory to Cytomegalovirus: Implications for Vaccine Development

et al. 2020

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Natural killer (NK) cells are innate lymphoid cells that recognize and eliminate virally-infected and cancerous cells. Members of the innate immune system are not usually considered to mediate immune memory, but over the past decade evidence has emerged that NK cells can do this in several contexts. Of these, the best understood and most widely accepted is the response to cytomegaloviruses, with strong evidence for memory to murine cytomegalovirus (MCMV) and several lines of evidence suggesting that the same is likely to be true of human cytomegalovirus (HCMV). The importance of NK cells in the context of HCMV infection is underscored by the armory of NK immune evasion genes encoded by HCMV aimed at subverting the NK cell immune response. As such, ongoing studies that have utilized HCMV to investigate NK cell diversity and function have proven instructive. Here, we discuss our current understanding of NK cell memory to viral infection with a focus on the response to cytomegaloviruses. We will then discuss the implications that this will have for the development of a vaccine against HCMV with particular emphasis on how a strategy that can harness the innate immune system and NK cells could be crucial for the development of a vaccine against this high-priority pathogen.

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Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination

Cited by 18 publications

References 19 publications

Durable natural killer cell responses after heterologous two-dose Ebola vaccination

Durable natural killer cell responses after heterologous two-dose Ebola vaccination

Regulation of the human NK cell compartment by pathogens and vaccines

NK Cell Memory to Cytomegalovirus: Implications for Vaccine Development

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