scholarly journals CD4+ T cells recognize unique and conserved 2009 H1N1 influenza hemagglutinin epitopes after natural infection and vaccination

2013 ◽  
Vol 25 (8) ◽  
pp. 447-457 ◽  
Author(s):  
Junbao Yang ◽  
Eddie James ◽  
Theresa J. Gates ◽  
Jonathan H. DeLong ◽  
Rebecca E. LaFond ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Natural Infection ◽  
H1n1 Influenza ◽  
Influenza Hemagglutinin ◽  
2009 H1n1

scholarly journals Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4+ T cells against the swine-origin H1N1 influenza virus

Vaccine ◽  
2011 ◽  
Vol 29 (17) ◽  
pp. 3299-3309 ◽  
Author(s):  
Brian C. Schanen ◽  
Anne S. De Groot ◽  
L. Moise ◽  
Matt Ardito ◽  
Elizabeth McClaine ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
In Silico ◽  
Cd4 T Cells ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus

scholarly journals A highly efficient T-cell immunoassay provides assessment of B cell help function of SARS-CoV-2 specific memory CD4+ T cells

2021 ◽  
Author(s):  
Asgar Ansari ◽  
Shilpa Sachan ◽  
Bimal Prasad Jit ◽  
Ashok Sharma ◽  
Poonam Coshic ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Cultured Cells ◽  
Natural Infection ◽  
Qualitative Assessment ◽  
Lectin Domain ◽  
Highly Efficient ◽  
Specific Memory ◽  
Memory Cd4 T Cells

The B cell help function of CD4+ T cells may serve as an immunologic correlate of protective adaptive immunity. The quantitative assessment of the B cell help potential of CD4+ T cells is limited by the lack of suitable antigen-specific functional assays. Here, we describe a highly efficient antigen-specific T-B co-cultures for quantitative measurement of T-dependent B cell responses. Using Mycobacterium tuberculosis specific setup, we show that early priming and activation of CD4+ T cells is important for the mutualistic collaboration between antigen-specific T and B cells, which could be achieved by supplementing the co-cultures with autologous monocytes. We further show that monocyte-derived growth factors provide the impetus for productive T-B collaboration by conferring optimal survivability in the cultured cells. This study provides first evidence of C‐type lectin domain family 11 member A (CLEC11A/SCGF) as an essential growth factor for B cell survival. Importantly, we demonstrate the successful translation of monocyte supplemented T-B co-cultures in qualitative assessment of SARS-CoV-2 specific memory CD4+ T cells by quantifying several correlates of productive T-B cross-talk like plasma cell output, secreted antibody, antibody secreting cells and IL21 secreting T cells. Thus, the method described here can provides qualitative assessment of SARS-CoV-2 spike CD4+ T cells after natural infection and can be applied to assess the B cell help function of memory CD4+ T cells generated in response to COVID-19 vaccine.

scholarly journals Peptide Epitope Hot Spots of CD4 T Cell Recognition Within Influenza Hemagglutinin During the Primary Response to Infection

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 220 ◽  
Author(s):  
Zackery A. G. Knowlden ◽  
Katherine A. Richards ◽  
Savannah A. Moritzky ◽  
Andrea J. Sant
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cd4 T Cells ◽  
H1n1 Influenza ◽  
Primary Response ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Peptide Epitope ◽  
Ha Protein

Antibodies specific for the hemagglutinin (HA) protein of influenza virus are critical for protective immunity to infection. Our studies show that CD4 T cells specific for epitopes derived from HA are the most effective in providing help for the HA-specific B cell responses to infection and vaccination. In this study, we asked whether HA epitopes recognized by CD4 T cells in the primary response to infection are equally distributed across the HA protein or if certain segments are enriched in CD4 T cell epitopes. Mice that collectively expressed eight alternative MHC (Major Histocompatibility Complex) class II molecules, that would each have different peptide binding specificities, were infected with an H1N1 influenza virus. CD4 T cell peptide epitope specificities were identified by cytokine EliSpots. These studies revealed that the HA-specific CD4 T cell epitopes cluster in two distinct regions of HA and that some segments of HA are completely devoid of CD4 T cell epitopes. When located on the HA structure, it appears that the regions that most poorly recruit CD4 T cells are sequestered within the interior of the HA trimer, perhaps inaccessible to the proteolytic machinery inside the endosomal compartments of antigen presenting cells.

scholarly journals Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

2021 ◽  
Author(s):  
Rajesh Vikkurthi ◽  
Asgar Ansari ◽  
Anupama R Pai ◽  
Someshwar Nath Jha ◽  
Shilpa Sachan ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Vaccine ◽  
Cd4 T Cells ◽  
Vaccine Development ◽  
Natural Infection ◽  
Immune Memory ◽  
Booster Immunization ◽  
Tfh Cells ◽  
Fold Reduction ◽  
Cellular Immune

The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in ~85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ~1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

scholarly journals Memory CD4 T Cells Direct Protective Responses to Influenza Virus in the Lungs through Helper-Independent Mechanisms

2010 ◽  
Vol 84 (18) ◽  
pp. 9217-9226 ◽  
Author(s):  
John R. Teijaro ◽  
David Verhoeven ◽  
Carly A. Page ◽  
Damian Turner ◽  
Donna L. Farber
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cd4 T Cells ◽  
Natural Infection ◽  
Influenza Virus Infection ◽  
Cd4 T Cell ◽  
Virus Challenge ◽  
Specific Memory ◽  
Memory Cd4 T Cells

ABSTRACT Memory CD4 T cells specific for influenza virus are generated from natural infection and vaccination, persist long-term, and recognize determinants in seasonal and pandemic influenza virus strains. However, the protective potential of these long-lived influenza virus-specific memory CD4 T cells is not clear, including whether CD4 T-cell helper or effector functions are important in secondary antiviral responses. Here we demonstrate that memory CD4 T cells specific for H1N1 influenza virus directed protective responses to influenza virus challenge through intrinsic effector mechanisms, resulting in enhanced viral clearance, recovery from sublethal infection, and full protection from lethal challenge. Mice with influenza virus hemagglutinin (HA)-specific memory CD4 T cells or polyclonal influenza virus-specific memory CD4 T cells exhibited protection from influenza virus challenge that occurred in the presence of CD8-depleting antibodies in B-cell-deficient mice and when CD4 T cells were transferred into lymphocyte-deficient RAG2−/− mice. Moreover, the presence of memory CD4 T cells mobilized enhanced T-cell recruitment and immune responses in the lung. Neutralization of gamma interferon (IFN-γ) production in vivo abrogated memory CD4 T-cell-mediated protection from influenza virus challenge by HA-specific memory T cells and heterosubtypic protection by polyclonal memory CD4 T cells. Our results indicate that memory CD4 T cells can direct enhanced protection from influenza virus infection through mobilization of immune effectors in the lung, independent of their helper functions. These findings have important implications for the generation of universal influenza vaccines by promoting long-lived protective CD4 T-cell responses.

scholarly journals Avian and Human Seasonal Influenza Hemagglutinin Proteins Elicit CD4 T Cell Responses That Are Comparable in Epitope Abundance and Diversity

2017 ◽  
Vol 24 (3) ◽  
Author(s):  
Anthony DiPiazza ◽  
Katherine Richards ◽  
Nicholas Poulton ◽  
Andrea J. Sant
Keyword(s):  
T Cells ◽  
T Cell ◽  
Avian Influenza ◽  
Cd4 T Cells ◽  
Influenza Viruses ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
Avian Influenza Viruses ◽  
Influenza Hemagglutinin ◽  
Unbiased Manner

ABSTRACT Avian influenza viruses remain a significant concern due to their pandemic potential. Vaccine trials have suggested that humans respond poorly to avian influenza vaccines relative to seasonal vaccines. It is important to understand, first, if there is a general deficiency in the ability of avian hemagglutinin (HA) proteins to generate immune responses and, if so, what underlies this defect. This question is of particular interest because it has been suggested that in humans, the poor immunogenicity of H7 vaccines may be due to a paucity of CD4 T cell epitopes. Because of the generally high levels of cross-reactive CD4 T cells in humans, it is not possible to compare the inherent immunogenicities of avian and seasonal HA proteins in an unbiased manner. Here, we empirically examine the epitope diversity and abundance of CD4 T cells elicited by seasonal and avian HA proteins. HLA-DR1 and HLA-DR4 transgenic mice were vaccinated with purified HA proteins, and CD4 T cells to specific epitopes were identified and quantified. These studies revealed that the diversity and abundance of CD4 T cells specific for HA do not segregate on the basis of whether the HA was derived from human seasonal or avian influenza viruses. Therefore, we conclude that failure in responses to avian vaccines in humans is likely due to a lack of cross-reactive CD4 T cell memory perhaps coupled with competition with or suppression of naive, HA-specific CD4 T cells by memory CD4 T cells specific for more highly conserved proteins.

scholarly journals A mutation in the receptor binding site enhances infectivity of 2009 H1N1 influenza hemagglutinin pseudotypes without changing antigenicity

Virology ◽  
2010 ◽  
Vol 407 (2) ◽  
pp. 374-380 ◽  
Author(s):  
Wei Wang ◽  
Juan A. Castelán-Vega ◽  
Alicia Jiménez-Alberto ◽  
Russell Vassell ◽  
Zhiping Ye ◽  
...  
Keyword(s):  
Binding Site ◽  
Receptor Binding ◽  
H1n1 Influenza ◽  
Receptor Binding Site ◽  
Influenza Hemagglutinin ◽  
2009 H1n1

scholarly journals Subsisting H1N1 influenza memory responses are insufficient to protect from pandemic H1N1 influenza challenge in C57BL/6 mice

2013 ◽  
Vol 94 (8) ◽  
pp. 1701-1711 ◽  
Author(s):  
Leo K. Sage ◽  
Julie M. Fox ◽  
Stephen M. Tompkins ◽  
Ralph A. Tripp
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
H1n1 Influenza ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Effector Memory ◽  
Pandemic H1n1 ◽  
T Cell Epitopes ◽  
2009 H1n1

The 2009 swine-origin pandemic H1N1 (pH1N1) influenza virus transmitted and caused disease in many individuals immune to pre-2009 H1N1 influenza virus. Whilst extensive studies on antibody-mediated pH1N1 cross-reactivity have been described, few studies have focused on influenza-specific memory T-cells. To address this, the immune response in pre-2009 H1N1 influenza-immune mice was evaluated after pH1N1 challenge and disease pathogenesis was determined. The results show that despite homology shared between pre-2009 H1N1 and pH1N1 strains, the effector memory T-cell response to pre-2009 H1N1 was generally ineffective, a finding that correlated with lung virus persistence. Additionally, pH1N1 challenge generated T-cells reactive to new pH1N1 epitopes. These studies highlight the importance of vaccinating against immunodominant T-cell epitopes to provide for a more effective strategy to control influenza virus through heterosubtypic immunity.

MHC class II tetramers containing influenza hemagglutinin and EBV EBNA1 epitopes detect reliably specific CD4+ T cells in healthy volunteers

2004 ◽  
Vol 65 (5) ◽  
pp. 507-513 ◽  
Author(s):  
Ming Ye ◽  
Suha Kasey ◽  
Sumit Khurana ◽  
Nga T Nguyen ◽  
Scott Schubert ◽  
...  
Keyword(s):  
T Cells ◽  
Healthy Volunteers ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Influenza Hemagglutinin
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