MF59- and Al(OH)3-Adjuvanted Staphylococcus aureus (4C-Staph) Vaccines Induce Sustained Protective Humoral and Cellular Immune Responses, with a Critical Role for Effector CD4 T Cells at Low Antibody Titers

AbstractMacrophage inflammatory protein-1α (MIP-1α) and MIP-1β are distinct but highly homologous CC chemokines produced by a variety of host cells in response to various external stimuli and share affinity for CCR5. To better elucidate the role of these CC chemokines in adaptive immunity, we have characterized the affects of MIP-1α and MIP-1β on cellular and humoral immune responses. MIP-1α stimulated strong antigen (Ag)–specific serum immunoglobulin G (IgG) and IgM responses, while MIP-1β promoted lower IgG and IgM but higher serum IgA and IgE antibody (Ab) responses. MIP-1α elevated Ag-specific IgG1 and IgG2b followed by IgG2a and IgG3 subclass responses, while MIP-1β only stimulated IgG1 and IgG2b subclasses. Correspondingly, MIP-1β produced higher titers of Ag-specific mucosal secretory IgA Ab levels when compared with MIP-1α. Splenic T cells from MIP-1α– or MIP-1β–treated mice displayed higher Ag-specific Th1 (interferon-γ [IFN-γ]) as well as selective Th2 (interleukin-5 [IL-5] and IL-6) cytokine responses than did T cells from control groups. Interestingly, mucosally derived T cells from MIP-1β–treated mice displayed higher levels of IL-4 and IL-6 compared with MIP-1α–treated mice. However, MIP-1α effectively enhanced Ag-specific cell-mediated immune responses. In correlation with their selective effects on humoral and cellular immune responses, these chemokines also differentially attract CD4+ versus CD8+ T cells and modulate CD40, CD80, and CD86 expressed by B220+ cells as well as CD28, 4-1BB, and gp39 expression by CD4+ and CD8+ T cells in a dose-dependent fashion. Taken together, these studies suggest that these CC chemokines differentially enhance mucosal and serum humoral as well as cellular immune responses.

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Viral Load, Antibody Titers and Recombinant Open Reading Frame 2 Protein-Induced Th1/Th2 Cytokines and Cellular Immune Responses in Self-Limiting and Fulminant Hepatitis E

Intervirology ◽

10.1159/000214862 ◽

2009 ◽

Vol 52 (2) ◽

pp. 78-85 ◽

Cited By ~ 63

Author(s):

S. Saravanabalaji ◽

A.S. Tripathy ◽

R.R. Dhoot ◽

M.S. Chadha ◽

A.L. Kakrani ◽

...

Keyword(s):

Viral Load ◽

Immune Responses ◽

Hepatitis E ◽

Open Reading Frame ◽

Th2 Cytokines ◽

Reading Frame ◽

Cellular Immune Responses ◽

Antibody Titers ◽

Cellular Immune ◽

Open Reading Frame 2

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Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.00421-07 ◽

2008 ◽

Vol 15 (3) ◽

pp. 452-459 ◽

Cited By ~ 4

Author(s):

Giulia Freer ◽

Donatella Matteucci ◽

Paola Mazzetti ◽

Francesca Tarabella ◽

Valentina Catalucci ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Immune Responses ◽

Immune Functions ◽

Peripheral Blood Mononuclear ◽

Challenge Virus ◽

Homologous Virus ◽

Antibody Titers ◽

Cellular Immune ◽

Antigen Presenting

ABSTRACT Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4+/CD8+ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

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Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽

10.3390/vaccines8010126 ◽

2020 ◽

Vol 8 (1) ◽

pp. 126

Author(s):

Lilin Lai ◽

Nadine Rouphael ◽

Yongxian Xu ◽

Amy C. Sherman ◽

Srilatha Edupuganti ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Influenza A ◽

Vaccine Dose ◽

T Cell Responses ◽

Post Vaccination ◽

Cell Responses ◽

Cellular Immune Responses ◽

Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

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Cellular immune responses against HCV: T cells take a diversion in the liver

Hepatology ◽

10.1002/hep.20498 ◽

2004 ◽

Vol 40 (6) ◽

pp. 1459-1461

Author(s):

Paul Klenerman ◽

Nasser Semmo ◽

Scott Ward

Keyword(s):

T Cells ◽

Immune Responses ◽

Cellular Immune Responses ◽

Cellular Immune

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Immune Responses Following Mouse Peripheral Nerve Xenotransplantation in Rats

Journal of Biomedicine and Biotechnology ◽

10.1155/2009/412598 ◽

2009 ◽

Vol 2009 ◽

pp. 1-4 ◽

Cited By ~ 10

Author(s):

Lai-Jin Lu ◽

Jia-Bing Sun ◽

Zhi-Gang Liu ◽

Xu Gong ◽

Jian-Li Cui ◽

...

Keyword(s):

Immune Responses ◽

Peripheral Nerve ◽

Effective Means ◽

Critical Role ◽

Moderate Increase ◽

Effector Cells ◽

Xenograft Rejection ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Th1 Cytokines

Xenotransplantation offers a potentially unlimited source for tissues and organs for transplantation, but the strong xenoimmune responses pose a major obstacle to its application in the clinic. In this study, we investigate the rejection of mouse peripheral nerve xenografts in rats. Severe intragraft mononuclear cell infiltration, graft distension, and necrosis were detected in the recipients as early as 2 weeks after mouse nerve xenotransplantation. The number of axons in xenografts reduced progressively and became almost undetectable at week 8. However, mouse nerve xenotransplantation only led to a transient and moderate increase in the production of Th1 cytokines, including IL-2, IFN-γ, and TNF-α. The data implicate that cellular immune responses play a critical role in nerve xenograft rejection but that further identification of the major effector cells mediating the rejection is required for developing effective means to prevent peripheral nerve xenograft rejection.

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