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1.
SSRN;
Preprint in English | SSRN | ID: ppcovidwho-325784

ABSTRACT

Background: Immunocompromised individuals including patients with hematological malignancies constitute a population at high risk of developing severe disease upon SARS-CoV-2 infection. Protection afforded by vaccination is frequently low. Methods: A patient cohort who had received bone marrow transplantation or CAR-T cells was studied following a 2-dose BNT162b2 mRNA vaccination and compared to healthy vaccine recipients. Anti-Spike antibody and systemic innate responses were compared in the two vaccine cohorts. Findings: The patients had significantly lower SARS-CoV-2 Spike antibodies to the Wuhan strain, with proportional lower cross-recognition of Beta, Delta, and Omicron Spike-RBD proteins. Both cohorts neutralized WA1 and Delta but not Omicron. Vaccination elicited an innate cytokine signature featuring IFN-γ, IL-15 and IP-10/CXCL10, but most patients showed a diminished systemic cytokine response. In patients who failed to develop antibodies, the innate systemic was dominated by IL-8 and MIP-1a with significant attenuation in the IFN-γ, IL-15 and IP-10/CXCL10 signature response. Changes in IFN-γ and and IP-10/CXCL10 at priming vaccination and IFN-γ, IL-15, IL-7 and IL-10 upon booster vaccination correlated with the Spike antibody magnitude and were predictive of successful antibody development. Interpretation: These data identified a cytokine hub featuring IFN-γ, IL-15 and IP-10/CXCL10 characterizing a response to the BNT162b2 mRNA vaccination. These data identify a cytokine signature as correlating with successful antibody development in patients with hematological disease treated with cell therapies. These approaches provide a tool to connect innate signatures associated with protective adaptive responses to vaccines. Funding Information: Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research (GNP, BKF). The funders had no role in the experimental design, collection of data or writing the paper. Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: The study protocol was approved by the ethics committee of Alexandra General Hospital (Ref No. 15/23 December 2020) and Evangelismos General Hospital (Ref No is 26/01-20-2021). The ethics committee of the Alexandra General Hospital approved the study protocol (Ref No. 15/23 December 2020). The study was carried out in accordance with the Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice standards of care. All participants provided written informed consent at study entry. Keywords: humoral response, cytokine, SARS-CoV-2 BNT162b2 mRNA vaccine, IFN-gamma, CXCL10, IL-15

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-306707

ABSTRACT

Early responses to vaccination are important in shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity and help optimizing efficacy of mRNA and other vaccine strategies. We characterized the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naïve vaccine recipients and individuals previously infected by COVID-19 (NCT04743388). Transient increases in IL-15 and IFN-γ levels early after boost correlated with Spike-RBD antibody levels, supporting their possible use as biomarkers of successful vaccination. We identified a systemic signature including IL-15, IFN-γ and IP-10/CXCL10 increase after the 1st vaccination, which was enriched by TNF-α and IL-6 after the 2nd vaccination. In vaccine recipients with history of COVID-19 infection, a single vaccine dose resulted in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naïve individuals, a result with potential implication for future public health recommendations.Funding Information: Funding: This research was supported [in part] by the IntramuralResearch Program of the NIH, NCI to G.N.P. and B.K.F.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: All study procedures were carried out in accordance with the declaration of Helsinki (18th World Medical Association Assembly), its subsequent amendments, the Greek regulations and guidelines, as well as the good clinical practice guidelines (GCP) as defined by the International Conference of Harmonization. The study was also approved by the local ethic committee of Alexandra General Hospital (no 15/23 December 2020).

3.
Cell Rep ; 36(6): 109504, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1491797

ABSTRACT

Early responses to vaccination are important for shaping both humoral and cellular protective immunity. Dissecting innate vaccine signatures may predict immunogenicity to help optimize the efficacy of mRNA and other vaccine strategies. Here, we characterize the cytokine and chemokine responses to the 1st and 2nd dose of the BNT162b2 mRNA (Pfizer/BioNtech) vaccine in antigen-naive and in previously coronavirus disease 2019 (COVID-19)-infected individuals (NCT04743388). Transient increases in interleukin-15 (IL-15) and interferon gamma (IFN-γ) levels early after boost correlate with Spike antibody levels, supporting their use as biomarkers of effective humoral immunity development in response to vaccination. We identify a systemic signature including increases in IL-15, IFN-γ, and IP-10/CXCL10 after the 1st vaccination, which were enriched by tumor necrosis factor alpha (TNF-α) and IL-6 after the 2nd vaccination. In previously COVID-19-infected individuals, a single vaccination results in both strong cytokine induction and antibody titers similar to the ones observed upon booster vaccination in antigen-naive individuals, a result with potential implication for future public health recommendations.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Chemokine CXCL10/immunology , Interferon-gamma/immunology , Interleukin-15/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/immunology , COVID-19/metabolism , COVID-19 Vaccines/administration & dosage , Female , Humans , Immunity/immunology , Male , Middle Aged , RNA, Messenger/immunology
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