Antigen-Specific T-Cell Responses in Humans after Intranasal Immunization with a Meningococcal Serogroup B Outer Membrane Vesicle Vaccine

ABSTRACT We have studied the ability of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine, when administered intranasally without adjuvant, to induce T-cell responses in humans. A group of 12 vaccinees was immunized with four doses of OMVs (250 μg of protein/dose) at weekly intervals, and a single booster dose was given 5 months later. In vitro T-cell proliferation in response to the OMV vaccine, purified PorA (class 1) protein, PorB (class 3) protein, and one unrelated control antigen (Mycobacterium bovis BCG) was measured by [3H]thymidine incorporation into peripheral blood mononuclear cells obtained from the vaccinees before and after the immunizations. The nasal OMV immunizations induced antigen-specific T-cell responses in the majority of the vaccinees when tested against OMVs (7 of 12) and the PorA antigen (11 of 12). None of the vaccinees showed a vaccine-induced T-cell response to the PorB antigen after the initial four doses. Although some individuals responded to all the vaccine antigens after the booster dose, this response was not significant when the vaccinees were analyzed as a group. We have also demonstrated that the PorA antigen-specific T-cell responses correlated with anti-OMV immunoglobulin A (IgA) levels in nasal secretions, with anti-OMV IgG levels in serum, and with serum bactericidal activity. In conclusion, we have shown that it is possible to induce antigen-specific T-cell responses in humans by intranasal administration of a meningococcal OMV vaccine without adjuvant.

Download Full-text

Human T-Cell Responses after Vaccination with the Norwegian Group B Meningococcal Outer Membrane Vesicle Vaccine

Infection and Immunity ◽

10.1128/iai.66.3.959-965.1998 ◽

1998 ◽

Vol 66 (3) ◽

pp. 959-965 ◽

Cited By ~ 31

Author(s):

Lisbeth Meyer Næss ◽

Fredrik Oftung ◽

Audun Aase ◽

Lee M. Wetzler ◽

Randi Sandin ◽

...

Keyword(s):

T Cell ◽

Outer Membrane ◽

Membrane Vesicle ◽

T Cell Responses ◽

Outer Membrane Vesicle ◽

Igg Antibody ◽

Cell Responses ◽

Human T Cell ◽

Group B ◽

Antibody Levels

ABSTRACT We have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group B Neisseria meningitidis outer membrane vesicle (OMV) vaccine. Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46). T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovisBCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination. The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein. The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively. Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose. We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r = 0.50, P < 0.0001, for OMV and PorA). In addition, we observed a progressive increase in the percentage of CD45R0+ (memory) CD4-positive T cells (P = 0.002). In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells.

Download Full-text

Human B- and T-cell responses after immunization with a hexavalent PorA meningococcal outer membrane vesicle vaccine.

Infection and Immunity ◽

10.1128/iai.65.12.5184-5190.1997 ◽

1997 ◽

Vol 65 (12) ◽

pp. 5184-5190 ◽

Cited By ~ 30

Author(s):

E R van der Voort ◽

H van Dijken ◽

B Kuipers ◽

J van der Biezen ◽

P van der Ley ◽

...

Keyword(s):

T Cell ◽

Outer Membrane ◽

Membrane Vesicle ◽

T Cell Responses ◽

Outer Membrane Vesicle ◽

Cell Responses

Download Full-text

Convergent epitope-specific T cell responses after SARS-CoV-2 infection and vaccination

10.1101/2021.07.12.21260227 ◽

2021 ◽

Author(s):

Anastasia A Minervina ◽

Mikhail V Pogorelyy ◽

Allison M Kirk ◽

Emma Kaitlynn Allen ◽

Kim J Allison ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mononuclear Cells ◽

T Cell Responses ◽

T Cell Response ◽

Critical Parameters ◽

T Cell Memory ◽

Cell Memory ◽

Cell Responses ◽

Depth Analysis

SARS-CoV-2 mRNA vaccines, including Pfizer/Biontech BNT162b2, were shown to be effective for COVID-19 prevention, eliciting both robust antibody responses in naive individuals and boosting pre-existing antibody levels in SARS-CoV-2-recovered individuals. However, the magnitude, repertoire, and phenotype of epitope-specific T cell responses to this vaccine, and the effect of vaccination on pre-existing T cell memory in SARS-CoV-2 convalescent patients, are still poorly understood. Thus, in this study we compared epitope-specific T cells elicited after natural SARS-CoV-2 infection, and vaccination of both naive and recovered individuals. We collected peripheral blood mononuclear cells before and after BNT162b2 vaccination and used pools of 18 DNA-barcoded MHC-class I multimers, combined with scRNAseq and scTCRseq, to characterize T cell responses to several immunodominant epitopes, including a spike-derived epitope cross-reactive to common cold coronaviruses. Comparing responses after infection or vaccination, we found that T cells responding to spike-derived epitopes show similar magnitudes of response, memory phenotypes, TCR repertoire diversity, and αβTCR sequence motifs, demonstrating the potency of this vaccination platform. Importantly, in COVID-19-recovered individuals receiving the vaccine, pre-existing spike-specific memory cells showed both clonal expansion and a phenotypic shift towards more differentiated CCR7-CD45RA+ effector cells. In-depth analysis of T cell receptor repertoires demonstrates that both vaccination and infection elicit largely identical repertoires as measured by dominant TCR motifs and receptor breadth, indicating that BNT162b2 vaccination largely recapitulates T cell generation by infection for all critical parameters. Thus, BNT162b2 vaccination elicits potent spike-specific T cell responses in naive individuals and also triggers the recall T cell response in previously infected individuals, further boosting spike-specific responses but altering their differentiation state. Overall, our study demonstrates the potential of mRNA vaccines to induce, maintain, and shape T cell memory through vaccination and revaccination.

Download Full-text

Expression of RHAMM and WT1 As Well As T Cell Responses to These Antigens Before and After Allogeneic Stem Cell Transplantation in Patients with Leukemia

Blood ◽

10.1182/blood.v118.21.4315.4315 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4315-4315

Author(s):

Rosaely Casalegno-Garduño ◽

Claudia Meier ◽

Jiju Mani ◽

Kersten Borchert ◽

Inken Hilgendorf ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Mononuclear Cells ◽

T Cell Responses ◽

T Cell Response ◽

Cell Responses ◽

Before And After

Abstract Abstract 4315 Introduction: Patients with leukemia undergo chemotherapy as first treatment. Approximately 70–80% of patients with acute myeloid leukemia (AML) reach complete remission. However, most of them will relapse and only 25% survive more than five years. Therefore, there is a need for novel approaches in the treatment of leukemia, such as immunotherapy. Leukemic blasts have an aberrant expression of antigens. They are called leukemia-associated antigens (LAAs) like the receptor for hyaluronan acid-mediated motility (RHAMM) and the Wilms’ tumor gene 1 product (WT1). Epitopes of these LAAs can be recognized by CD8+ T cells. MATERIAL AND METHODS: In the present study, we analyzed the correlation between the clinical course of 18 patients suffering from leukemia (10 AML, 5 MDS, 1 ALL and 2 B-CLL) with the expression of RHAMM and WT1 transcripts before and after allogeneic stem cell transplantation (allo-SCT). Gene transcripts were measured by quantitative real time PCR (RQ-PCR) from RNA of peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) samples. Antigen specific T cells were enriched in a mixed lymphocyte-peptide culture (MLPC) and antigen specific T cell responses were measured by enzyme-linked immunosorbent spot (ELISPOT). Results: We observed a reduction in WT1 transcripts in both PBMC and BMMC after transplantation in all of the WT1 positive patients (6/18 patients: 33%). Four of these six WT1+ patients (67%) remained in complete remission (CR) with low transcripts of WT1 (PBMC: lower than 14 WT1 copies/104 ABL copies, BMMC: lower than 202 WT1 copies/104 ABL copies). In contrast, 2 of 6 WT1+ patients (33%) showed an increase (PBMC: up to 98 WT1 copies/104 ABL copies, BMMC: up to 920 WT1 copies/104 ABL copies) of WT1 transcripts eventually resulting in a relapse. Specific T cell responses were detected against WT1 in two of three WT1+ patients in the presence of blasts (before transplantation or in relapse). However, these specific responses vanished while the patients reached a CR. Furthermore, RHAMM+ patients (12/18: 67%) showed different patterns when correlated with clinical status. Five patients (42%) showed gradually increased levels of RHAMM transcripts during CR. No RHAMM specific T cells could be detected in this group (2/2 MLPCs). Four patients (33%) showed a decrease in the transcripts of RHAMM when they reached a CR. One of these patients developed a T cell response to RHAMM three months after allo-SCT (2/2 MLPCs). One patient showed high transcripts of RHAMM and WT1 during the diagnosis, WT1 transcripts were reduced after allo-SCT. Both RHAMM and WT1 transcripts gradually increased until the patients died. We could detect in this patient both WT1 and RHAMM-specific T cells before transplantation. After allo-SCT the T cell response vanished. CONCLUSION: Taken together, WT1 is a suitable marker for minimal residual disease after allo-SCT. One might speculate that T cells specific for WT1 vanished during the CR due to the absence of the antigen to stimulate the proliferation of specific T cell population. Moreover, the presence of RHAMM-specific T cells may help to maintain a CR. In both cases vaccination with RHAMM and WT1 derived peptide might enhance T cell responses in the patient leading to a better outcome of the patient. Disclosures: Freund: Medac: Honoraria, Research Funding.

Download Full-text

Vaccination of cattle with attenuated rinderpest virus stimulates CD4+ T cell responses with broad viral antigen specificity

Journal of General Virology ◽

10.1099/0022-1317-81-9-2137 ◽

2000 ◽

Vol 81 (9) ◽

pp. 2137-2146 ◽

Cited By ~ 18

Author(s):

Brett T. Lund ◽

Ashok Tiwari ◽

Sareen Galbraith ◽

Michael D. Baron ◽

W. Ivan Morrison ◽

...

Keyword(s):

T Cell ◽

Vaccine Strain ◽

Mononuclear Cells ◽

Virulent Strain ◽

T Cell Responses ◽

T Cell Response ◽

Specific Response ◽

Antigen Specificity ◽

Rinderpest Virus ◽

Cell Responses

The immune responses of cattle inoculated with either a virulent or an attenuated vaccine strain of rinderpest virus (RPV) were examined by measuring the proliferation of peripheral blood mononuclear cells (PBMC) to whole RPV antigen preparations and to individual RPV major structural proteins expressed using recombinant adenoviruses. Responses to the T cell mitogen concanavalin A (ConA) were also measured as a control to monitor non-specific effects of infection with RPV on T cell responses. Infection with the vaccine strain of RPV was found to induce a strong CD4+ T cell response. A specific response was detected to all RPV proteins tested, namely the haemagglutinin (H), fusion (F), nucleocapsid (N) and matrix (M) proteins, in animals vaccinated with the attenuated strain of the virus. No one protein was found to be dominant with respect to the induction of T cell proliferative responses. As expected, vaccination of cattle with an unrelated virus vaccine, a capripox vaccine, failed to produce a response to RPV antigens. While profound suppression of T cell responses was observed following infection with the virulent strain of RPV, no evidence of impairment of T cell responsiveness was observed following RPV vaccination, or on subsequent challenge of vaccinated animals with virulent virus.

Download Full-text

Tracking of Peptide-Specific CD4+ T-Cell Responses after an Acute Resolving Viral Infection: a Study of Parvovirus B19

Journal of Virology ◽

10.1128/jvi.01173-06 ◽

2006 ◽

Vol 80 (22) ◽

pp. 11209-11217 ◽

Cited By ~ 17

Author(s):

Victoria Kasprowicz ◽

Adiba Isa ◽

Thomas Tolfvenstam ◽

Katie Jeffery ◽

Paul Bowness ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mononuclear Cells ◽

Ex Vivo ◽

Parvovirus B19 ◽

Acute Infection ◽

T Cell Responses ◽

T Cell Response ◽

Immunoglobulin M ◽

Cell Responses

ABSTRACT The evolution of peptide-specific CD4+ T-cell responses to acute viral infections of humans is poorly understood. We analyzed the response to parvovirus B19 (B19), a ubiquitous and clinically significant pathogen with a compact and conserved genome. The magnitude and breadth of the CD4+ T-cell response to the two B19 capsid proteins were investigated using a set of overlapping peptides and gamma interferon-specific enzyme-linked immunospot assays of peripheral blood mononuclear cells (PBMCs) from a cohort of acutely infected individuals who presented with acute arthropathy. These were compared to those for a cohort of B19-specific immunoglobulin M-negative (IgM−), IgG+ remotely infected individuals. Both cohorts of individuals were found to make broad CD4+ responses. However, while the responses following acute infection were detectable ex vivo, responses in remotely infected individuals were only detected after culture. One epitope (LASEESAFYVLEHSSFQLLG) was consistently targeted by both acutely (10/12) and remotely (6/7) infected individuals. This epitope was DRB1*1501 restricted, and a major histocompatibility complex peptide tetramer stained PBMCs from acutely infected individuals in the range of 0.003 to 0.042% of CD4+ T cells. Tetramer-positive populations were initially CD62Llo; unlike the case for B19-specific CD8+ T-cell responses, however, CD62L was reexpressed at later times, as responses remained stable or declined slowly. This first identification of B19 CD4+ T-cell epitopes, including a key immunodominant peptide, provides the tools to investigate the breadth, frequency, and functions of cellular responses to this virus in a range of specific clinical settings and gives an important reference point for analysis of peptide-specific CD4+ T cells during acute and persistent virus infections of humans.

Download Full-text

Patterns of Cellular Immunity Associated with Experimental Infection with rDEN2Δ30 (Tonga/74) Support Its Suitability as a Human Dengue Virus Challenge Strain

Journal of Virology ◽

10.1128/jvi.02133-16 ◽

2017 ◽

Vol 91 (8) ◽

Cited By ~ 14

Author(s):

Alba Grifoni ◽

Michael Angelo ◽

John Sidney ◽

Sinu Paul ◽

Bjoern Peters ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

Cellular Immunity ◽

Mononuclear Cells ◽

Natural Infection ◽

T Cell Responses ◽

T Cell Response ◽

Nonstructural Proteins ◽

Challenge Strain ◽

Cell Responses

ABSTRACT A deletion variant of the dengue virus (DENV) serotype 2 (DENV2) Tonga/74 strain lacking 30 nucleotides from its 3′ untranslated region (rDEN2Δ30) has previously been established for use in a controlled human DENV challenge model. To evaluate if this model is appropriate for the derivation of correlates of protection for DENV vaccines on the basis of cellular immunity, we wanted to compare the cellular immune response to this challenge strain to the response induced by natural infection. To achieve this, we predicted HLA class I- and class II-restricted peptides from rDEN2Δ30 and used them in a gamma interferon enzyme-linked immunosorbent spot assay to interrogate CD8+ and CD4+ T cell responses in healthy volunteers infected with rDEN2Δ30. At the level of CD8 responses, vigorous ex vivo responses were detected in approximately 80% of donors. These responses were similar in terms of the magnitude and the numbers of epitopes recognized to the responses previously observed in peripheral blood mononuclear cells from donors from regions where DENV is hyperendemic. The similarity extended to the immunodominance hierarchy of the DENV nonstructural proteins, with NS3, NS5, and NS1 being dominant in both donor cohorts. At the CD4 level, the responses to rDEN2Δ30 vaccination were less vigorous than those to natural DENV infection and were more focused on nonstructural proteins. The epitopes recognized following rDEN2Δ30 infection and natural infection were largely overlapping for both the CD8 (100%) and CD4 (85%) responses. Finally, rDEN2Δ30 induced stronger CD8 responses than other, more attenuated DENV isolates. IMPORTANCE The lack of a known correlate of protection and the failure of a neutralizing antibody to correlate with protection against dengue virus have highlighted the need for a human DENV challenge model to better evaluate the candidate live attenuated dengue vaccines. In this study, we sought to characterize the immune profiles of rDEN2Δ30-infected subjects and to compare the profiles with those for subjects from areas where DENV is hyperendemic. Our data demonstrate that T cell responses to rDENV2Δ30 are largely similar to those to natural infection in terms of specificity, highlighting that the response to this virus in humans is appropriate as a model for the T cell response to primary DENV2 infection.

Download Full-text

CD4+ T-Lymphocyte and Immunoglobulin G2 Responses in Calves Immunized with Anaplasma marginale Outer Membranes and Protected against Homologous Challenge

Infection and Immunity ◽

10.1128/iai.66.11.5406-5413.1998 ◽

1998 ◽

Vol 66 (11) ◽

pp. 5406-5413 ◽

Cited By ~ 111

Author(s):

Wendy C. Brown ◽

Varda Shkap ◽

Daming Zhu ◽

Travis C. McGuire ◽

Wenbin Tuo ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Outer Membrane ◽

Outer Membrane Proteins ◽

T Cell Responses ◽

Anaplasma Marginale ◽

T Cell Response ◽

Helper T Cell ◽

Outer Membranes ◽

Cell Responses

ABSTRACT Protective immunity against the ehrlichial pathogenAnaplasma marginale has been hypothesized to require induction of immunoglobulin G2 (IgG2) antibody against outer membrane protein epitopes and coordinated activation of macrophages for phagocytosis and killing. In the present study, cell-mediated immune responses, including induction of IgG isotype switching, were characterized in calves immunized with purified outer membranes of the Florida strain of A. marginale. Importantly, these calves were subsequently shown to be protected upon experimental challenge with the Florida strain, and calves which developed the highest IgG2 titers were completely protected against infection. Peripheral blood mononuclear cells (PBMC) obtained after immunization proliferated strongly in response to both whole A. marginale homogenates and purified outer membranes, and this responsiveness persisted until the time of challenge. Responding cells were shown to be CD4+ T cells, and CD4+ T-cell lines cultured for 2 to 4 weeks also proliferated specifically in response to A. marginale and produced high titers of gamma interferon. The helper T-cell response included recognition of conserved epitopes, as PBMC proliferation was stimulated by the homologous Florida strain, four genetically distinct A. marginale strains, and Anaplasma ovis. The outer membrane proteins stimulating the PBMC responses in protected calves included major surface proteins (MSPs) MSP-1, MSP-2, and MSP-3, which were previously shown to induce partial protection against infection. These studies demonstrate, for the first time, potent helper T-cell responses in cattle protectively immunized with outer membranes against A. marginale challenge and identify three MSPs that are recognized by immune T cells. These experiments provide the basis for subsequent identification of the helper T-cell epitopes on MSP-1, MSP-2, and MSP-3 that are needed to evoke anamnestic antibody and effector T-cell responses elicited by protein or nucleic acid immunization.

Download Full-text

Development and Characterization of a Novel Non-Lytic Cancer Immunotherapy Using a Recombinant Arenavirus Vector Platform

Frontiers in Oncology ◽

10.3389/fonc.2021.732166 ◽

2021 ◽

Vol 11 ◽

Author(s):

Henning Lauterbach ◽

Sarah Schmidt ◽

Kia Katchar ◽

Xiaoping Qing ◽

Corinne Iacobucci ◽

...

Keyword(s):

T Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Phase 1 ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

T Cell Response ◽

Cell Responses ◽

Antigen Presenting

Engineered viral vectors represent a promising strategy to trigger antigen-specific antitumor T cell responses. Arenaviruses have been widely studied because of their ability to elicit potent and protective T cell responses. Here, we provide an overview of a novel intravenously administered, replication-competent, non-lytic arenavirus-based vector technology that delivers tumor antigens to induce antigen-specific anti-cancer T cell responses. Preclinical studies in mice and cell culture experiments with human peripheral blood mononuclear cells demonstrate that arenavirus vectors preferentially infect antigen-presenting cells. This, in conjunction with a non-lytic functional activation of the infected antigen-presenting cells, leads to a robust antigen-specific CD8+ T cell response. T cell migration to, and infiltration of, the tumor microenvironment has been demonstrated in various preclinical tumor models with vectors encoding self- and non–self-antigens. The available data also suggest that arenavirus–based vector therapy can induce immunological memory protecting from tumor rechallenge. Based on promising preclinical data, a phase 1/2 clinical trial was initiated and is currently ongoing to test the activity and safety of arenavirus vectors, HB-201 and HB-202, created using lymphocytic choriomeningitis virus and Pichinde virus, respectively. Both vectors have been engineered to deliver non-oncogenic versions of the human papilloma virus 16 (HPV16) antigens E7 and E6 and will be injected intravenously with or without an initial intratumoral dose. This dose escalation/expansion study is being conducted in patients with recurrent or metastatic HPV16+ cancers. Promising preliminary data from this ongoing clinical study have been reported. Immunogenicity data from several patients demonstrate that a single injection of HB-201 or HB-202 monotherapy is highly immunogenic, as evidenced by an increase in inflammatory cytokines/chemokines and the expansion of antigen-specific CD8+ T cell responses. This response can be further enhanced by alternating injections of HB-202 and HB-201, which has resulted in frequencies of circulating HPV16 E7/E6-specific CD8+ T cells of up to 40% of the total CD8+ T cell compartment in peripheral blood in analyses to date. Treatment with intravenous administration also resulted in a disease control rate of 73% among 11 evaluable patients with head and neck cancer dosed every three weeks, including 2 patients with a partial response.

Download Full-text

T-cell mediated immunity after AZD1222 vaccination: A polyfunctional spike-specific Th1 response with a diverse TCR repertoire

10.1101/2021.06.17.21259027 ◽

2021 ◽

Author(s):

Phillip A. Swanson ◽

Marcelino Padilla ◽

Wesley Hoyland ◽

Kelly McGlinchey ◽

Paul A. Fields ◽

...

Keyword(s):

T Cell ◽

Mononuclear Cells ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Response ◽

Spike Protein ◽

Cell Mediated Immunity ◽

Peripheral Blood Mononuclear ◽

Adult Age ◽

Cell Responses

AZD1222 (ChAdOx1 nCoV-19), a replication-deficient simian adenovirus-vectored vaccine, has demonstrated safety, efficacy, and immunogenicity against coronavirus disease 2019 (COVID-19) in clinical trials and real-world studies. We characterized CD4+ and CD8+ T-cell responses induced by AZD1222 vaccination in peripheral blood mononuclear cells (PBMCs) from 280 unique vaccine recipients aged 18-85 years who enrolled in the phase 2/3 COV002 trial. Total spike-specific CD4+ T cell helper type 1 (Th1) and CD8+ T-cell responses were significantly increased in AZD1222-vaccinated adults of all ages following two doses of AZD1222. CD4+ Th2 responses following AZD1222 vaccination were not detected. Furthermore, AZD1222-specific Th1 and CD8+ T cells both displayed a high degree of polyfunctionality in all adult age groups. T-cell receptor (TCR) β ; sequences from vaccinated participants mapped against TCR sequences known to react to SARS-CoV-2 revealed substantial breadth and depth across the SARS-CoV-2 spike protein for the AZD1222-induced CD4+ and CD8+ T-cell responses. Overall, AZD1222 vaccination induced a robust, polyfunctional Th1-dominated T-cell response, with broad CD4+ and CD8+ T-cell coverage across the SARS-CoV-2 spike protein.

Download Full-text