A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses, while a weak TCR response seemed to presage a weak antibody response. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.

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Suppression by Thimerosal of Ex-Vivo CD4+ T Cell Response to Influenza Vaccine and Induction of Apoptosis in Primary Memory T Cells

PLoS ONE ◽

10.1371/journal.pone.0092705 ◽

2014 ◽

Vol 9 (4) ◽

pp. e92705 ◽

Cited By ~ 5

Author(s):

Emily Loison ◽

Béatrice Poirier-Beaudouin ◽

Valérie Seffer ◽

Audrey Paoletti ◽

Vered Abitbol ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Influenza Vaccine ◽

Cell Response ◽

Memory T Cells ◽

Ex Vivo ◽

T Cell Response ◽

Primary Memory ◽

Cd4 T Cell ◽

Induction Of Apoptosis

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Immunization with a Mixture of HIV Env DNA and VLP Vaccines Augments Induction of CD8 T Cell Responses

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/497219 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Ling Ye ◽

Zhiyuan Wen ◽

Ke Dong ◽

Lei Pan ◽

Zhigao Bu ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Dna Vaccine ◽

Cell Response ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Response ◽

Antibody Responses ◽

Cell Responses ◽

Virus Like Particle

The immune response induced by immunization with HIV Env DNA and virus-like particle (VLP) vaccines was investigated. Immunization with the HIV Env DNA vaccine induced a strong CD8 T cell response but relatively weak antibody response against the HIV Env whereas immunization with VLPs induced higher levels of antibody responses but little CD8 T cell response. Interestingly, immunization with a mixture the HIV Env DNA and VLP vaccines induced enhanced CD8 T cell and antibody responses. Further, it was observed that the mixing of DNA and VLP vaccines during immunization is necessary for augmenting induction of CD8 T cell responses and such augmentation of CD8 T cell responses was also observed by mixing the HIV Env DNA vaccine with control VLPs. These results show that immunization with a mixture of DNA and VLP vaccines combines advantages of both vaccine platforms for eliciting high levels of both antibody and CD8 T cell responses.

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Superior antigen-specific CD4+T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older

BMC Infectious Diseases ◽

10.1186/1471-2334-14-425 ◽

2014 ◽

Vol 14 (1) ◽

Cited By ~ 24

Author(s):

Robert B Couch ◽

José M Bayas ◽

Covadonga Caso ◽

Innocent Nnadi Mbawuike ◽

Concepción Núñez López ◽

...

Keyword(s):

T Cell ◽

Influenza Vaccine ◽

Cell Response ◽

Randomised Trial ◽

T Cell Response ◽

Cd4 T Cell ◽

Trivalent Influenza Vaccine

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Direct and indirect immune effects of CMP-001, a virus-like particle containing a TLR9 agonist

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-002484 ◽

2021 ◽

Vol 9 (6) ◽

pp. e002484

Author(s):

Shakoora A Sabree ◽

Andrew P Voigt ◽

Sue E Blackwell ◽

Ajaykumar Vishwakarma ◽

Michael S Chimenti ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

Cell Response ◽

T Cell Response ◽

Cd4 T Cell ◽

T Cell Proliferation ◽

Secondary Effects ◽

Tlr9 Agonist ◽

Virus Like Particle ◽

Enhanced Expression

BackgroundCMP-001, also known as vidutolimod, is a virus-like particle containing a TLR9 agonist that is showing promise in early clinical trials. Our group previously demonstrated that the immunostimulatory effects of CMP-001 are dependent on an anti-Qβ antibody response which results in opsonization of CMP-001 and uptake by plasmacytoid dendritic cells (pDCs) that then produce interferon (IFN)-α. IFN-α then leads to an antitumor T-cell response that is responsible for the in vivo efficacy of CMP-001. Here, we explore mechanisms by which the initial effects of CMP-001 on pDCs activate other cells that can contribute to development of an antitumor T-cell response.MethodsUptake of CMP-001 by various peripheral blood mononuclear cell (PBMC) populations and response to anti-Qβ-coated CMP-001 were evaluated by flow cytometry and single-cell RNA sequencing. Purified monocytes were treated with anti-Qβ-coated CMP-001 or recombinant IFN-α to evaluate direct and secondary effects of anti-Qβ-coated CMP-001 on monocytes.ResultsMonocytes had the highest per cell uptake of anti-Qβ-coated CMP-001 with lower levels of uptake by pDCs and other cell types. Treatment of PBMCs with anti-Qβ-coated CMP-001 induced upregulation of IFN-responsive genes including CXCL10, PDL1, and indoleamine-2,3-dioxygenase (IDO) expression by monocytes. Most of the impact of anti-Qβ-coated CMP-001 on monocytes was indirect and mediated by IFN-α, but uptake of anti-Qβ-coated CMP-001 altered the monocytic response to IFN-α and resulted in enhanced expression of PDL1, IDO, and CD80 and suppressed expression of CXCL10. These changes included an enhanced ability to induce autologous CD4 T-cell proliferation.ConclusionsAnti-Qβ-coated CMP-001 induces IFN-α production by pDCs which has secondary effects on a variety of cells including monocytes. Uptake of anti-Qβ-coated CMP-001 by monocytes alters their response to IFN-α, resulting in enhanced expression of PDL1, IDO and CD80 and suppressed expression of CXCL10. Despite aspects of an immunosuppressive phenotype, these monocytes demonstrated increased ability to augment autologous CD4 T-cell proliferation. These findings shed light on the complexity of the mechanism of action of anti-Qβ-coated CMP-001 and provide insight into pathways that may be targeted to further enhance the efficacy of this novel approach to immunotherapy.

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