scholarly journals Immune Responses following Neonatal DNA Vaccination Are Long-Lived, Abundant, and Qualitatively Similar to Those Induced by Conventional Immunization

2000 ◽  
Vol 74 (6) ◽  
pp. 2620-2627 ◽  
Author(s):  
Daniel E. Hassett ◽  
Jie Zhang ◽  
Mark Slifka ◽  
J. Lindsay Whitton
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Ex Vivo ◽  
Humoral Response ◽  
Dna Vaccination ◽  
Protective Capacity ◽  
Live Virus ◽  
Virus Challenge ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACT Virus infections are devastating to neonates, and the induction of active antiviral immunity in this age group is an important goal. Here, we show that a single neonatal DNA vaccination induces cellular and humoral immune responses which are maintained for a significant part of the animal's life span. We employ a sensitive technique which permits the first demonstration and quantitation, directly ex vivo, of virus-specific CD8+ T cells induced by DNA immunization. One year postvaccination, antigen-specific CD8+ T cells were readily detectable and constituted 0.5 to 1% of all CD8+ T cells. By several criteria—including cytokine production, perforin content, development of lytic ability, and protective capacity—DNA vaccine-induced CD8+ memory T cells were indistinguishable from memory cells induced by immunization with a conventional (live-virus) vaccine. Analyses of long-term humoral immune responses revealed that, in contrast to the strong immunoglobulin G2a (IgG2a) skewing of the humoral response seen after conventional vaccination, IgG1 and IgG2a levels were similar in DNA-vaccinated neonatal and adult animals, indicating a balanced T helper response. Collectively, these results show that a single DNA vaccination within hours or days of birth can induce long-lasting CD8+ T- and B-cell responses; there is no need for secondary immunization (boosting). Furthermore, the observed immune responses induced in neonates and in adults are indistinguishable by several criteria, including protection against virus challenge.

scholarly journals Noninfectious X4 but Not R5 Human Immunodeficiency Virus Type 1 Virions Inhibit Humoral Immune Responses in Human Lymphoid Tissue Ex Vivo

2004 ◽  
Vol 78 (13) ◽  
pp. 7061-7068 ◽  
Author(s):  
Wendy Fitzgerald ◽  
Andrew W. Sylwester ◽  
Jean-Charles Grivel ◽  
Jeffrey D. Lifson ◽  
Leonid B. Margolis
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Human Lymphoid Tissue ◽  
Hiv 1

ABSTRACT Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4+ T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4+ T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4+ T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.

scholarly journals TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomohisa Okamura ◽  
Shuji Sumitomo ◽  
Kaoru Morita ◽  
Yukiko Iwasaki ◽  
Mariko Inoue ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals REGULATION OF THE IMMUNE RESPONSE

1973 ◽  
Vol 137 (3) ◽  
pp. 721-739 ◽  
Author(s):  
Michael Hoffmann ◽  
John W. Kappler
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Immune Suppression ◽  
Antigen Recognition ◽  
Helper T Cells ◽  
Antibody Specificity ◽  
Humoral Immune ◽  
Functional Assays ◽  
Humoral Immune Responses

The specificity of antigen recognition by thymus-derived helper cells (T cells) and antibody was examined in mice, heterologous erythrocyte antigens from sheep (SRBC), goat (GRBC), burro (BRBC), chicken (CRBC), and toad (TRBC) being used. Antibody specificity was tested by a number of functional assays: hemagglutination, hemolysis, and immune suppression. The specificity of T cells was determined by titrating their ability to help the in vitro antitrinitrophenol (TNP) responses of mouse spleen cultures immunized with the hapten coupled to the various test erythrocytes as carrier. Anti-SRBC antibody cross-reacted with GRBC, but not with BRBC, CRBC, or TRBC. In contrast, SRBC-primed helper T cells cross-reacted with both GRBC and BRBC, but not with CRBC or TRBC, indicating a difference in the specificity of antigen recognition between the cellular and the humoral immune responses.

scholarly journals NFAT control of immune function: New Frontiers for an Abiding Trooper

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 260 ◽  
Author(s):  
Martin Vaeth ◽  
Stefan Feske
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Immune Responses ◽  
Physiological Function ◽  
Large Body ◽  
Immunological Tolerance ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Humoral Immune ◽  
Humoral Immune Responses

Nuclear factor of activated T cells (NFAT) was first described almost three decades ago as a Ca2+/calcineurin-regulated transcription factor in T cells. Since then, a large body of research uncovered the regulation and physiological function of different NFAT homologues in the immune system and many other tissues. In this review, we will discuss novel roles of NFAT in T cells, focusing mainly on its function in humoral immune responses, immunological tolerance, and the regulation of immune metabolism.

Relative Potency of Cellular and Humoral Immune Responses Induced by DNA Vaccination

Intervirology ◽  
2000 ◽  
Vol 43 (4-6) ◽  
pp. 227-232 ◽  
Author(s):  
Gillis R. Otten ◽  
Barbara Doe ◽  
Mary Schaefer ◽  
Minchao Chen ◽  
Mark J. Selby ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccination ◽  
Relative Potency ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals CD40L-deficient mice show deficits in antiviral immunity and have an impaired memory CD8+ CTL response.

1996 ◽  
Vol 183 (5) ◽  
pp. 2129-2142 ◽  
Author(s):  
P Borrow ◽  
A Tishon ◽  
S Lee ◽  
J Xu ◽  
I S Grewal ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Cd4 T Cells ◽  
Antiviral Immunity ◽  
Ctl Response ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Deficient Mice

The ligand for CD40 (CD40L) is expressed on the surface of activated CD4+ T cells and its role in T-B cell collaborations and thymus-dependent humoral immunity is well established. Recently, by generating CD40L-knockout mice, we have confirmed its previously described role in humoral immunity and defined another important function of this molecule in the in vivo clonal expansion of antigen-specific CD4+ T cells. Here, we investigated the potential in vivo role of CD40L in antiviral immunity by examining the immune response mounted by CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV), Pichinde virus, or vesicular stomatitis virus. Humoral immune responses of CD40L-deficient mice to these viruses were severely compromised, although moderate titres of antiviral IgM and some IgG2a were produced by virus-infected CD40L-deficient mice by a CD4+ T cell-independent mechanism. By contrast, CD40L-deficient mice made strong primary CTL responses to all three viruses. Interestingly however, although memory CTL activity was detectable in CD40L-deficient mice two months after infection with LCMV, the memory CTL response was much less efficient than in wild-type mice. Together, the results show that CD40-CD40L interactions are required for strong antiviral humoral immune responses, and reveal a novel role for CD40L in the establishment and/or maintenance of CD8+ CTL memory.

scholarly journals Intradermal DNA Vaccination Enhanced by Low-Current Electroporation Improves Antigen Expression and Induces Robust Cellular and Humoral Immune Responses

2012 ◽  
Vol 23 (9) ◽  
pp. 943-950 ◽  
Author(s):  
Natalie A. Hutnick ◽  
Devin J.F. Myles ◽  
Bernadette Ferraro ◽  
Colleen Lucke ◽  
Feng Lin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Expression ◽  
Dna Vaccination ◽  
Humoral Immune ◽  
Humoral Immune Responses
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