Innate and adaptive immune defects associated with lower SARS-CoV-2 BNT162b2 mRNA vaccine response in elderly people

The immune factors associated with impaired SARS-CoV-2 vaccine response in the elderly are mostly unknown. We studied old and young people vaccinated with SARS-CoV-2 BNT162b2 mRNA before and after the first and second dose. Aging was associated with a lower anti-RBD IgG levels and a decreased magnitude and polyfunctionality of SARS-CoV-2 specific T cell response. The dramatic decrease in thymic function in the elderly, which fueled alteration in T cell homeostasis, and lower CD161+ T cell levels were associated with decreased T cell response two months after vaccination. Additionally, a deficient dendritic cell (DC) homing, activation and Toll like receptor (TLR)-mediated function, along with a proinflammatory functional profile in monocytes, were observed in the elderly, which was also related to lower specific T cell response after vaccination. These findings might be relevant for the improvement of the current vaccination strategies and for the development of new vaccine prototypes.

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Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralising antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms

10.1101/2021.04.27.21256096 ◽

2021 ◽

Author(s):

Patrick Harrington ◽

Hugues de Lavallade ◽

Katie Doores ◽

Amy O'Reilly ◽

Jeffrey Seow ◽

...

Keyword(s):

T Cell ◽

Cell Response ◽

Myeloproliferative Neoplasms ◽

T Cell Response ◽

The Novel ◽

Neutralising Antibodies ◽

Cell Responses ◽

Disease Subtype ◽

Immune Defects ◽

First Time

Encouraging results have been observed from initial studies evaluating vaccines targeting the novel beta coronavirus which causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, concerns have been raised around the efficacy of these vaccines in immunosuppressed populations, including patients with haematological malignancy. Myeloproliferative neoplasms (MPN), in particular myelofibrosis (MF), are associated with heterogenous immune defects which are influenced by patient age, disease subtype and the use of cytoreductive therapies. Patients with a WHO defined diagnosis of an MPN presenting to our clinic were recruited following first injection of 30μg BNT162b2. A positive anti-S IgG ELISA was seen in 76.1% (16) of patients following vaccination with positive neutralising antibodies detected in 85.7% (18) of patients. A memory T cell response was observed in 80% (16) of patients, with a CD4+ T cell response in 75% (15) and a CD8+ T cell response in 35% (7). These results, for the first time, provide some reassurance regarding the initial immune response to the BNT162b2 vaccine amongst patients with MPN, with response rates similar to that observed in the general population.

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Rapid T Cell Response to Vaccination Can Occur without Antibody Response in Children Post HSCT.

Blood ◽

10.1182/blood.v104.11.2235.2235 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2235-2235

Author(s):

W. Nicholas Haining ◽

J. Evans ◽

N. Seth ◽

G. Callaway ◽

K. Wucherpfennig ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Cell Response ◽

Influenza A ◽

T Cell Response ◽

T Cell Memory ◽

Cell Immunity ◽

Before And After ◽

B Cell Response

Abstract Vaccination is widely used to improve pathogen-specific immunity in patients post HSCT, but it is not known whether patients can mount an effective T cell response to vaccine antigens (vAg). Moreover the relationship between T and B cell response to vAg has not been studied. We hypothesized that a sufficiently sensitive assay of T cell response to vAg would allow vaccination to be used as a tool to measure immune recovery post HSCT and improve vaccine design. We therefore: (1) developed a flow-cytometry-based approach to quantify and characterize T cells specific for vAg; (2) validated it by measuring T cell immunity to influenza A in normal donors; and (3) characterized the T and B cell response to influenza vaccination in pediatric HSCT patients. PBMC were labeled with CFSE and stimulated in vitro with whole influenza Ag. Ag-specific T cells were sensitively detected by their proliferation (loss of CFSE fluorescence) and simultaneous expression of the activation marker HLA-DR. Proliferating/active T cells could be readily detected after stimulation with influenza A Ag in healthy adult (n=4) and pediatric (n=19) donors but were absent in control conditions. Both CD4+ and CD8+ T cell proliferation was detected in all donors but one, and in children as young as 6mo. Staining with MHC I- and MHC II-tetramers confirmed that the proliferating/active population contained T cells specific for immunodominant CD8+ and CD4+ epitopes, demonstrating that vAg were processed and presented to epitope-specific T cells. To characterize the phenotype of influenza-specific T cell memory, we separated memory and naive CD4+ cells prior to antigen-stimulation. Antigen-experienced (CD45RA−/CCR7−) but not naive (CD45RA+/CCR7+) T cells proliferated to vAg confirming that the assay detected pre-existing influenza-A-specific T cell memory. We next assessed Influenza-A-specific T cell immunity before and after influenza vaccination in five pediatric HSCT recipients (mean age 10.6y, range 5–15y; mean time from transplant 13m, range 3–21m). Prior to vaccination the CD4 proliferation to influenza-A was a mean of 3.3% (range 0.04–11%). Following vaccination CD4 proliferation increased significantly in all patients (mean 19.0%, range 6.9%–31.8%, p=0.02). This increase was specific as proliferation to control Ag was unchanged. Influenza-A CD8+ proliferation also increased in 3 of 5 patients but was not statistically significant for the group consistent with the limited efficacy of soluble vAg in inducing CD8+ T cell response. All patients had detectable influenza-A-specific IgG levels prior to vaccination but despite a T cell response to vaccination in all patients, none had a significant increase in IgG level following vaccination. Only one patient had an IgM response; this patient also had the highest influenza-A-specific CD4 proliferation before and after immunization suggesting that there may be a threshold of T cell response required for a B cell response. Using a novel assay we demonstrate that a T cell response to vaccination can occur without an accompanying B cell response. This assay provides a more sensitive measure of immunity to vaccination and allows vaccine response to be used as a benchmark of strategies to accelerate post-HSCT T cell reconstitution.

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The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook

Journal of Immunology Research ◽

10.1155/2020/9470102 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Hager Mohamed ◽

Vandana Miller ◽

Stephen R. Jennings ◽

Brian Wigdahl ◽

Fred C. Krebs

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Dendritic Cell ◽

Cell Response ◽

T Cell Response ◽

Phagocytic Cells ◽

Adaptive Immune ◽

Dc Vaccine ◽

Infected Cells ◽

Hiv 1

Dendritic cells (DC) are key phagocytic cells that play crucial roles in both the innate and adaptive immune responses against the human immunodeficiency virus type 1 (HIV-1). By processing and presenting pathogen-derived antigens, dendritic cells initiate a directed response against infected cells. They activate the adaptive immune system upon recognition of pathogen-associated molecular patterns (PAMPs) on infected cells. During the course of HIV-1 infection, a successful adaptive (cytotoxic CD8+ T-cell) response is necessary for preventing the progression and spread of infection in a variety of cells. Dendritic cells have thus been recognized as a valuable tool in the development of immunotherapeutic approaches and vaccines effective against HIV-1. The advancements in dendritic cell vaccines in cancers have paved the way for applications of this form of immunotherapy to HIV-1 infection. Clinical trials with patients infected with HIV-1 who are well-suppressed by antiretroviral therapy (ART) were recently performed to assess the efficacy of DC vaccines, with the goal of mounting an HIV-1 antigen-specific T-cell response, ideally to clear infection and eliminate the need for long-term ART. This review summarizes and compares methods and efficacies of a number of DC vaccine trials utilizing autologous dendritic cells loaded with HIV-1 antigens. The potential for advancement and novel strategies of improving efficacy of this type of immunotherapy is also discussed.

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Preferential CD8 rather than CD4 T-cell response to wear particles of polyether-ether-ketone and highly cross-linked polyethylene

RSC Advances ◽

10.1039/c7ra10589d ◽

2018 ◽

Vol 8 (4) ◽

pp. 1866-1874 ◽

Cited By ~ 3

Author(s):

Zhe Du ◽

Shujun Wang ◽

You Wang

Keyword(s):

Immune Response ◽

T Cell ◽

Cell Response ◽

Adaptive Immune Response ◽

T Cell Response ◽

Cd4 T Cell ◽

Wear Particles ◽

Adaptive Immune ◽

Polyether Ether Ketone ◽

Ether Ketone

Enriching the understanding of the effects of the particles on the adaptive immune response.

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Delayed Antibody and T-Cell Response to BNT162b2 Vaccination in the Elderly, Germany

Emerging Infectious Diseases ◽

10.3201/eid2708.211145 ◽

2021 ◽

Vol 27 (8) ◽

pp. 2174-2178

Author(s):

Tatjana Schwarz ◽

Pinkus Tober-Lau ◽

David Hillus ◽

Elisa T. Helbig ◽

Lena J. Lippert ◽

...

Keyword(s):

T Cell ◽

Cell Response ◽

The Elderly ◽

T Cell Response

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ANALYSIS OF HCV-SPECIFIC T CELL RESPONSE IN LIVER TRANSPLANT RECIPIENTS BEFORE AND AFTER ANTIVIRAL TREATMENT (PEGIFN + RIBAVIRIN).

Transplantation Journal ◽

10.1097/00007890-200607152-02312 ◽

2006 ◽

Vol 82 (Suppl 2) ◽

pp. 833

Author(s):

&NA;

Keyword(s):

T Cell ◽

Liver Transplant ◽

Cell Response ◽

Antiviral Treatment ◽

T Cell Response ◽

Transplant Recipients ◽

Before And After ◽

Liver Transplant Recipients

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Abstract 2761: Antibody and T cell response profiling in pancreatic cancer patients before and after chemotherapy identify tumor associated antigens suitable for immunotherapy

10.1158/1538-7445.am2018-2761 ◽

2018 ◽

Author(s):

Sara Bulfamante ◽

Giorgia Mandili ◽

Moitza Principe ◽

Daniele Giordano ◽

Emanuela Mazza ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Cell ◽

Cancer Patients ◽

Cell Response ◽

T Cell Response ◽

Tumor Associated Antigens ◽

Before And After

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Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a “vaccinal effect” of rituximab

Blood ◽

10.1182/blood-2008-10-185280 ◽

2009 ◽

Vol 113 (16) ◽

pp. 3809-3812 ◽

Cited By ~ 109

Author(s):

Shannon P. Hilchey ◽

Ollivier Hyrien ◽

Tim R. Mosmann ◽

Alexandra M. Livingstone ◽

Jonathan W. Friedberg ◽

...

Keyword(s):

T Cell ◽

Follicular Lymphoma ◽

Cell Response ◽

Cellular Response ◽

T Cell Response ◽

Passive Immunotherapy ◽

Cell Kill ◽

Before And After ◽

Anti Cd20 ◽

Universal Application

Abstract The incorporation of rituximab, a chimeric anti-CD20 monoclonal antibody, into the therapeutic armamentarium for patients with follicular lymphoma (FL) has significantly improved treatment outcome for such patients. Despite the almost universal application of this therapy, however, its exact mechanism of action has not been completely defined. One proposed mechanism is that of a “vaccinal” effect, whereby FL cell kill by rituximab results in the elicitation of an FL-specific T-cell response. The demonstration that rituximab can even elicit such a response in patients has, to our knowledge, never been shown. We analyzed the response against the immunoglobulin expressed by the FL before and after rituximab monotherapy in 5 FL patients and found an increase in FL idiotype–specific T cells after rituximab in 4 of 5 patients. Our data thus provide “proof of principle” for the ability of passive immunotherapy with rituximab to elicit an active FL-specific cellular response.

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