Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2806-2813 ◽  
Author(s):  
Gianfranco Di Genova ◽  
Joanna Roddick ◽  
Feargal McNicholl ◽  
Freda K. Stevenson
Keyword(s):  
Antibody Production ◽  
Protective Immunity ◽  
Cytokine Production ◽  
Human Subjects ◽  
Cellular Responses ◽  
T Helper ◽  
Purified Protein Derivative ◽  
Cell Responses ◽  
Common Antigens

AbstractHuman subjects maintain long-term immunologic memory against infective organisms but the mechanism is unclear. CD4+ T-helper memory (Thmem) cells are pivotal in controlling humoral and cellular responses, therefore their longevity and response to vaccination are critical for maintenance of protective immunity. To probe the dynamics of the Thmem-cell response to antigenic challenge, we investigated subjects following a booster injection with tetanus toxoid (TT). Expansion of TT-specific Thmem cells and cytokine production showed complex kinetics. Strikingly, parallel expansion and cytokine production occurred in pre-existing Thmem cells specific for 2 other common antigens: purified protein derivative of tuberculin and Candida albicans. Bystander expansion occurred in Thmem but not in Thnaive cells. Antibody production against TT peaked approximately 2 weeks after vaccination and gradually declined. However, pre-existing antibody against the other antigens did not change. It appears that although all Thmem cells are readily stimulated to expand, antibody responses are controlled by antigen availability. These findings relate to the maintenance of memory and have consequences for assessments of specific T-cell responses to vaccination.

scholarly journals One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

2021 ◽  
Vol 10 (15) ◽  
pp. 3305
Author(s):  
Andreas Rank ◽  
Athanasia Tzortzini ◽  
Elisabeth Kling ◽  
Christoph Schmid ◽  
Rainer Claus ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Early Time ◽  
T Helper ◽  
Persistent Symptoms ◽  
Cell Responses ◽  
One Year ◽  
Antibody Levels

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.

scholarly journals Effective and Long-Lasting Immunity against the Parasite Leishmania major in CD8-Deficient Mice

1998 ◽  
Vol 66 (8) ◽  
pp. 3968-3970 ◽  
Author(s):  
Magdalena Huber ◽  
Emma Timms ◽  
Tak W. Mak ◽  
Martin Röllinghoff ◽  
Michael Lohoff
Keyword(s):  
T Cells ◽  
Primary Infection ◽  
Leishmania Major ◽  
T Helper ◽  
T Helper 1 ◽  
Cell Responses ◽  
Deficient Mice ◽  
Parasite Leishmania

ABSTRACT The results of earlier investigations that tested whether CD8+ T cells are required in the defense againstLeishmania major have been inconsistent. We used CD8-deficient mice to directly address this issue. After primary infection with L. major, CD8-deficient mice controlled the infection for over 1 year and mounted strong T helper 1 cell responses. Thus, CD8+ T cells are not required for the long-term control of a primary infection with L. major.

scholarly journals Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2233 ◽  
Author(s):  
Nicole Brooks ◽  
Jennifer Hsu ◽  
Sandra Esparon ◽  
Dodie Pouniotis ◽  
Geoffrey Pietersz
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Tandem Repeat ◽  
T Cell Responses ◽  
Variable Number ◽  
T Helper ◽  
Cell Responses ◽  
Helper Epitope ◽  
Cell Penetrating

Peptide-based vaccines for cancer have many advantages however, for optimization these immunogens should incorporate peptide epitopes that induce CD8, as well as CD4 responses, antibody and long term immunity. Cell penetrating peptides (CPP) with a capacity of cytosolic delivery have been used to deliver antigenic peptides and proteins to antigen presenting cells to induce cytotoxic T cell, helper T cell and humoral responses in mice. For this study, a tripartite CPP including a mucin 1 (MUC1) variable number of tandem repeat (VNTR) containing multiple T cell epitopes and tetanus toxoid universal T helper epitope peptide (tetCD4) was synthesised (AntpMAPMUC1tet) and immune responses investigated in mice. Mice vaccinated with AntpMAPMUC1tet + CpG show enhanced antigen-specific interferon-gamma (IFN-γ) and IL-4 T cell responses compared with AntpMAPMUC1tet vaccination alone and induced a Th1 response, characterised by a higher ratio of IgG2a antibody/IgG1 antibodies. Furthermore, vaccination generated long term MUC1-specific antibody and T cell responses and delayed growth of MUC1+ve tumours in mice. This data demonstrates the efficient delivery of branched multiple antigen peptides incorporating CPP and that the addition of CpG augments immune responses.

scholarly journals The Immunoregulation of Th17 in Host against Intracellular Bacterial Infection

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yonghong Li ◽  
Chaojun Wei ◽  
Hui Xu ◽  
Jing Jia ◽  
Zhenhong Wei ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Bacterial Infections ◽  
Cytokine Production ◽  
T Helper ◽  
T Regulatory Cell ◽  
T Helper 17 ◽  
Socioeconomic Burden ◽  
Production Pattern ◽  
Underlying Mechanisms

T helper 17 cells (Th17) constitute a distinct subset of helper T cells with a unique transcriptional profile (STAT3, RORγ, and RORα), cytokine production pattern (IL17 family), and requirement of specific cytokines for their differentiation (TGF-β, IL6, IL21, and IL23). Recent studies involving experimental animals and humans have shown that Th17/IL17 plays a crucial role in host defense against a variety of pathogens, including bacteria and viruses. The underlying mechanisms by which Th17 performs include dendritic cell (DC) regulation, neutrophil recruitment, Th1 modulation, and T regulatory cell (Treg) balance. In recent years, researchers have generated an accumulating wealth of evidence on the role of Th17/IL17 in protective immunity to intracellular bacterial pathogens, such asMycobacterium tuberculosisandChlamydia trachomatis, which are one of the most important pathogens that inflict significant socioeconomic burden across the globe. In this article, we reviewed the current literature on the functions and mechanisms by which Th17/IL17 responds to intracellular bacterial infections. A better understanding of Th17/IL17 immunity to pathogens would be crucial for developing effective prophylactics and therapeutics.

scholarly journals Long-term protective immunity induced by an adjuvant-containing live-attenuated AIDS virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomotaka Okamura ◽  
Yuya Shimizu ◽  
Masamitsu N. Asaka ◽  
Tomohiro Kanuma ◽  
Yusuke Tsujimura ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Immune Responses ◽  
Protective Immunity ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Aids Virus ◽  
Cynomolgus Macaques ◽  
Cd8 Depletion

AbstractThe use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.

Control of Immunity by the Microbiota

2021 ◽  
Vol 39 (1) ◽  
pp. 449-479
Author(s):  
Eduard Ansaldo ◽  
Taylor K. Farley ◽  
Yasmine Belkaid
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Microbial Communities ◽  
Adaptive Immunity ◽  
Immune Recognition ◽  
T Helper ◽  
Cell Responses ◽  
Temporal Windows

The immune system has coevolved with extensive microbial communities living on barrier sites that are collectively known as the microbiota. It is increasingly clear that microbial antigens and metabolites engage in a constant dialogue with the immune system, leading to microbiota-specific immune responses that occur in the absence of inflammation. This form of homeostatic immunity encompasses many arms of immunity, including B cell responses, innate-like T cells, and conventional T helper and T regulatory responses. In this review we summarize known examples of innate-like T cell and adaptive immunity to the microbiota, focusing on fundamental aspects of commensal immune recognition across different barrier sites. Furthermore, we explore how this cross talk is established during development, emphasizing critical temporal windows that establish long-term immune function. Finally, we highlight how dysregulation of immunity to the microbiota can lead to inflammation and disease, and we pinpoint outstanding questions and controversies regarding immune system–microbiota interactions.

scholarly journals SARS-CoV-2 Vaccines Elicit Durable Immune Responses in Infant Rhesus Macaques

2021 ◽  
Author(s):  
Carolina Garrido ◽  
Alan D. Curtis ◽  
Maria Dennis ◽  
Sachi H. Pathak ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Rhesus Macaques ◽  
Herd Immunity ◽  
Cellular Responses ◽  
Infectious Dose ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
High Magnitude ◽  
Infant Rhesus

AbstractEarly life SARS-CoV-2 vaccination has the potential to provide lifelong protection and achieve herd immunity. To evaluate SARS-CoV-2 infant vaccination, we immunized two groups of 8 infant rhesus macaques (RMs) at weeks 0 and 4 with stabilized prefusion SARS-CoV-2 S-2P spike (S) protein, either encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or mixed with 3M-052-SE, a TLR7/8 agonist in a squalene emulsion (Protein+3M-052-SE). Neither vaccine induced adverse effects. High magnitude S-binding IgG and neutralizing infectious dose 50 (ID50) >103 were elicited by both vaccines. S-specific T cell responses were dominated by IL-17, IFN-γ, or TNF-α. Antibody and cellular responses were stable through week 22. The S-2P mRNA-LNP and Protein-3M-052-SE vaccines are promising pediatric SARS-CoV-2 vaccine candidates to achieve durable protective immunity.One-Sentence SummarySARS-CoV-2 vaccines are well-tolerated and highly immunogenic in infant rhesus macaques

scholarly journals Live-Attenuated Influenza Vaccine Induces Tonsillar Follicular T Helper Cell Responses That Correlate With Antibody Induction

2019 ◽  
Vol 221 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Sarah Lartey ◽  
Fan Zhou ◽  
Karl A Brokstad ◽  
Kristin G-I Mohn ◽  
Steffen A Slettevoll ◽  
...  
Keyword(s):  
Hemagglutination Inhibition ◽  
Inverse Correlation ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Helper ◽  
Post Vaccination ◽  
Cell Responses ◽  
Tfh Cells

Abstract Background Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. Methods We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. Results We report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. Conclusions Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans.

Long-Term Follow-up for Immunity After Monovalent or Combined Live Measles, Mumps, and Rubella Virus Vaccines

PEDIATRICS ◽  
1975 ◽  
Vol 56 (3) ◽  
pp. 380-387
Author(s):  
Robert E. Weibel ◽  
Eugene B. Buynak ◽  
Arlene A. McLean ◽  
Maurice R. Hilleman
Keyword(s):  
Rubella Virus ◽  
Protective Immunity ◽  
Human Subjects ◽  
Natural Infection ◽  
Rubella Vaccine ◽  
Mumps Vaccine ◽  
Long Term Follow Up ◽  
Substantial Decline

Antibody in human subjects persisted without substantial decline for 8 years after mumps vaccine (Jeryl Lynn), for 6 years after measles (Attenuvax), for 5½ years after rubella vaccine (HPV-77 duck), for 5 years after measles-mumps-rubella and mumps-rubella combined vaccines, for 4 years after measles and rubella, and for 2 years after measles-mumps vaccines, the longest periods tested. Protective immunity against mumps illness persisted through the eighth year. The patterns for antibody following vaccination parallel those for natural infection and indicate that immunity will be lasting. Subclinical reinfection evidenced by antibody increase was commonly seen in persons who had been vaccinated, much as follows the natural infection.

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