Targeting natural killer cells to enhance vaccine responses

Cox, Andrew D.; Cevik, Hilal; Feldman, H. Alex; Canaday, Laura M.; Lakes, Nora; Waggoner, Stephen N.

doi:10.1016/j.tips.2021.06.004

Cited by 33 publications

(32 citation statements)

References 108 publications

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“…Numerous studies demonstrate that NK cells, through the release of IFNγ, potentiate vaccine efficacy by promoting the differentiation of CD4 + T cells, isotype switching and differentiation into antibodysecreting cells of B cells, and the antigen-presenting functions of myeloid cells. 20 In agreement with recent reports 21 we also detected a significant increase of the plasmatic levels of MCP-1/CCL2, one of the key chemokines that regulate migration and infiltration of monocytes/ macrophages. However, the MCP-1 concentration and the monocyte blood count were comparable in the fast and the slow responders.…”

Section: Discussionsupporting

confidence: 92%

“…A likely source of IFN‐γ were the NK cells that expanded after the first injection only in the fast responders (Figure 2C). Numerous studies demonstrate that NK cells, through the release of IFN‐γ, potentiate vaccine efficacy by promoting the differentiation of CD4 + T cells, isotype switching and differentiation into antibody‐secreting cells of B cells, and the antigen‐presenting functions of myeloid cells 20 . In agreement with recent reports 21 we also detected a significant increase of the plasmatic levels of MCP‐1/CCL2, one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.…”

Section: Discussionsupporting

confidence: 92%

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Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID‐19 vaccine

Flego

Cesaroni

Romiti

et al. 2022

Journal of Thrombosis and Haemostasis

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Background A rapid immune response is critical to ensure effective protection against COVID‐19. Platelets are first‐line sentinels of the vascular system able to rapidly alert and stimulate the immune system. However, their role in the immune response to vaccines is not known. Objective To identify features of the platelet‐immune crosstalk that would provide an early readout of vaccine efficacy in adults who received the mRNA‐based COVID‐19 vaccine (BNT162b2). Methods We prospectively enrolled 11 young healthy volunteers (54% females, median age: 28 years) who received two doses of BNT162b2, 21 days apart, and we studied their platelet and immune response before and after each dose of the vaccine (3 and 10 ± 2 days post‐injection), in relation to the kinetics of the humoral response. Results Participants achieving an effective level of neutralizing antibodies before the second dose of the vaccine (fast responders) had a higher leukocyte count, mounted a rapid cytokine response that incremented further after the second dose, and an elevated platelet turnover that ensured platelet count stability. Their circulating platelets were not more reactive but expressed lower surface levels of the immunoreceptor tyrosine‐based inhibitory motif (ITIM)‐coupled receptor CD31 (PECAM‐1) compared to slow responders, and formed specific platelet‐leukocyte aggregates, with B cells, just 3 days after the first dose, and with non‐classical monocytes and eosinophils. Conclusion We identified features of the platelet‐immune crosstalk that are associated with the development of a rapid humoral response to an mRNA‐based vaccine (BNT162b2) and that could be exploited as early biomarkers of vaccine efficacy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID‐19 vaccine

Flego

Cesaroni

Romiti

et al. 2022

Journal of Thrombosis and Haemostasis

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“…Furthermore, the ability of NK cells to regulate other cells of the immune system has been increasingly recognized (Waggoner et al 2011 ). In the present context, they have been demonstrated to contribute to the regulation of vaccine-elicited T cell and B cell responses (Wagstaffe et al 2018 ; Cox et al 2021 ). Additionally, NK cells isolated from healthy individuals are now used as therapeutic agents in clinical trials involving human malignant (Ljunggren and Malmberg 2007 ; Myers and Miller 2021 ) and viral diseases including COVID-19 (Market et al 2020 ; Soleimanian and Yaghobi 2020 ).…”

Section: Introductionmentioning

confidence: 98%

NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Cuapio

Boulouis

Filipovic

et al. 2022

Mol Med

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Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.

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“…Our study demonstrated that IFN-γ expressions in NK cells after 1 st jab correlated with SARS-CoV-2 vaccine-induced neutralizing antibody, which echoes previous findings. Since NK cells may play essential roles in developing efficacious vaccine-induced protection, there are discussions about NK cell-mediated modulation of the immune response and its implication on immunization strategies and the development of next-generation vaccines ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination

Shen

Yen

et al. 2022

Front. Immunol.

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BackgroundInnate immunity, armed with pattern recognition receptors including Toll-like receptors (TLR), is critical for immune cell activation and the connection to anti-microbial adaptive immunity. However, information regarding the impact of age on the innate immunity in response to SARS-CoV2 adenovirus vector vaccines and its association with specific immune responses remains scarce.MethodsFifteen subjects between 25-35 years (the young group) and five subjects between 60-70 years (the older adult group) were enrolled before ChAdOx1 nCoV-19 (AZD1222) vaccination. We determined activation markers and cytokine production of monocyte, natural killer (NK) cells and B cells ex vivo stimulated with TLR agonist (poly (I:C) for TLR3; LPS for TLR4; imiquimod for TLR7; CpG for TLR9) before vaccination and 3-5 days after each jab with flow cytometry. Anti-SARS-CoV2 neutralization antibody titers (surrogate virus neutralization tests, sVNTs) were measured using serum collected 2 months after the first jab and one month after full vaccination.ResultsThe older adult vaccinees had weaker vaccine-induced sVNTs than young vaccinees after 1st jab (47.2±19.3% vs. 21.2±22.2%, p value<0.05), but this difference became insignificant after the 2nd jab. Imiquimod, LPS and CpG strongly induced CD86 expression in IgD+CD27- naïve and IgD-CD27+ memory B cells in the young group. In contrast, only the IgD+ CD27- naïve B cells responded to these TLR agonists in the older adult group. Imiquimode strongly induced the CD86 expression in CD14+ monocytes in the young group but not in the older adult group. After vaccination, the young group had significantly higher IFN-γ expression in CD3- CD56dim NK cells after the 1st jab, whilst the older adult group had significantly higher IFN-γ and granzyme B expression in CD56bright NK cells after the 2nd jab (all p value <0.05). The IFN-γ expression in CD56dim and CD56bright NK cells after the first vaccination and CD86 expression in CD14+ monocyte and IgD-CD27-double-negative B cells after LPS and imiquimod stimulation correlated with vaccine-induced antibody responses.ConclusionsThe innate immune responses after the first vaccination correlated with the neutralizing antibody production. Older people may have defective innate immune responses by TLR stimulation and weak or delayed innate immune activation profile after vaccination compared with young people.

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Targeting natural killer cells to enhance vaccine responses

Cited by 33 publications

References 108 publications

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID‐19 vaccine

Platelet and immune signature associated with a rapid response to the BNT162b2 mRNA COVID‐19 vaccine

NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals

Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination

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