scholarly journals Archaeosome Vaccine Adjuvants Induce Strong Humoral, Cell-Mediated, and Memory Responses: Comparison to Conventional Liposomes and Alum

2000 ◽  
Vol 68 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Lakshmi Krishnan ◽  
Chantal J. Dicaire ◽  
Girishchandra B. Patel ◽  
G. Dennis Sprott
Keyword(s):  
Immune Responses ◽  
Lipid Vesicles ◽  
Interleukin 4 ◽  
Molar Ratio ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Vaccine Adjuvants ◽  
Strong Response ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

ABSTRACT Ether glycerolipids extracted from various archaeobacteria were formulated into liposomes (archaeosomes) possessing strong adjuvant properties. Mice of varying genetic backgrounds, immunized by different parenteral routes with bovine serum albumin (BSA) entrapped in archaeosomes (∼200-nm vesicles), demonstrated markedly enhanced serum anti-BSA antibody titers. These titers were often comparable to those achieved with Freund's adjuvant and considerably more than those with alum or conventional liposomes (phosphatidylcholine-phosphatidylglycerol-cholesterol, 1.8:0.2:1.5 molar ratio). Furthermore, antigen-specific immunoglobulin G1 (IgG1), IgG2a, and IgG2b isotype antibodies were all induced. Association of BSA with the lipid vesicles was required for induction of a strong response, and >80% of the protein was internalized within most archaeosome types, suggesting efficient release of antigen in vivo. Encapsulation of ovalbumin and hen egg lysozyme within archaeosomes showed similar immune responses. Antigen-archaeosome immunizations also induced a strong cell-mediated immune response: antigen-dependent proliferation and substantial production of cytokines gamma interferon (Th1) and interleukin-4 (IL-4) (Th2) by spleen cells in vitro. In contrast, conventional liposomes induced little cell-mediated immunity, whereas alum stimulated only an IL-4 response. In contrast to alum and Freund's adjuvant, archaeosomes composed of Thermoplasma acidophilum lipids evoked a dramatic memory antibody response to the encapsulated protein (at ∼300 days) after only two initial immunizations (days 0 and 14). This correlated with increased antigen-specific cell cycling of CD4+ T cells: increase in synthetic (S) and mitotic (G2/M) and decrease in resting (G1) phases. Thus, archaeosomes may be potent vaccine carriers capable of facilitating strong primary and memory humoral, and cell-mediated immune responses to the entrapped antigen.

scholarly journals Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice

2001 ◽  
Vol 69 (10) ◽  
pp. 6427-6433 ◽  
Author(s):  
Mardjan Arvand ◽  
Ralf Ignatius ◽  
Thomas Regnath ◽  
Helmut Hahn ◽  
Martin E. A. Mielke
Keyword(s):  
Immune Responses ◽  
Bartonella Henselae ◽  
Interleukin 4 ◽  
Infection Model ◽  
Antibody Concentration ◽  
Specific Cell ◽  
Spleen Cells ◽  
Viable Bacteria ◽  
Igg Isotypes

ABSTRACT Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killedBartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation withBartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselaeinduces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

Antibodies to Indolealkylamines; Serotonin and Melatonin

1974 ◽  
Vol 52 (3) ◽  
pp. 196-202 ◽  
Author(s):  
Lee J. Grota ◽  
Gregory M. Brown
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Molar Ratio ◽  
Double Immunodiffusion ◽  
Protein Conjugates ◽  
Spectrophotometric Data ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Serotonin, N-acetyl serotonin, and 5-methoxy-N-acetyl serotonin (melatonin) were conjugated to bovine serum albumin (BSA) using formaldehyde. The molar ratio of hapten to protein was determined spectrophotometrically. Spectrophotometric data indicated that serotonin and N-acetyl serotonin but not melatonin were conjugated to bovine serum albumin. Selected hapten–protein conjugates were suspended in Freund's adjuvant and injected into rabbits. Antisera were harvested monthly and screened by double immunodiffusion. Immunodiffusion and inhibition tests indicated that antibodies raised to serotonin–BSA reacted with serotonin and 5-methoxytryptamine but failed to cross react with N-acetyl serotonin or melatonin. Inhibition tests indicated that antibodies to N-acetyl serotonin – BSA reacted with N-acetyl serotonin and cross reacted with melatonin but not with serotonin or 5-methoxytryptamine.

Cord blood stem-cell-derived dendritic cells generate potent antigen-specific immune responses and anti-tumour effects

2012 ◽  
Vol 123 (6) ◽  
pp. 347-360 ◽  
Author(s):  
Ming-Cheng Chang ◽  
Chien-Nan Lee ◽  
Yu-Li Chen ◽  
Ying-Cheng Chiang ◽  
Wei-Zen Sun ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Cord Blood ◽  
Antigen Presentation ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Cytotoxic T Cell ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Surface Markers

The aim of the present study was to investigate whether CBSCs [(umbilical) cord blood stem cells] can be a new source of DCs (dendritic cells), which can generate more potent antigen-specific immune responses and anti-tumour effects. CBSCs and PBMCs (peripheral blood mononuclear cells) were collected, cultured and differentiated into DCs. Surface markers, secreting cytokines, antigen-presentation activity, antigen-specific cell-mediated immunity and cytotoxic killing effects induced by these two DC origins were evaluated and compared. CBSCs were expanded ~17-fold by ex vivo culture. The expression of surface markers in CBSC-derived DCs were higher than those in PBMC-derived DCs treated with LPS (lipopolysaccharide). The CBSC-derived DCs mainly secreted IL (interleukin)-6, IL-10 and TNF (tumour necrosis factor)-α, whereas PBMC-derived DCs mainly secreted IL-5 and IFN (interferon)-γ. The CBSC-derived DCs had better antigen-presentation abilities when stimulated with LPS or TNF-α, induced higher numbers of IFN-γ-secreting antigen-specific CD8+ T-cells, as assessed using an ELISpot (enzyme-linked immunosorbent spot) assay, and stimulated more potent antigen-specific CTL (cytotoxic T-cell) activities (P<0.01, one-way ANOVA). CBSC-derived DCs had quicker and greater ERK (extracellular-signal-regulated kinase) and Akt phosphorylation, and weaker p38 phosphorylation, than PBMC-derived DCs when stimulated with LPS. In conclusion, CBSC-derived DCs have the ability to induce stronger antigen-specific immunity and more potent anti-tumour effects and therefore could be a good source of DCs for use in DC-based cancer vaccines and immunotherapy.

scholarly journals Altering the Cellular Location of an Antigen Expressed by a DNA-Based Vaccine Modulates the Immune Response

1999 ◽  
Vol 73 (12) ◽  
pp. 10214-10223 ◽  
Author(s):  
P. J. Lewis ◽  
S. van Drunen Littel-van den Hurk ◽  
L. A. Babiuk
Keyword(s):  
Lymph Node ◽  
Immune Responses ◽  
Dna Vaccines ◽  
Interleukin 4 ◽  
Cell Mediated Immunity ◽  
Bovine Herpesvirus 1 ◽  
Draining Lymph Node ◽  
Herpesvirus 1 ◽  
Draining Lymph Nodes ◽  
Node Immunization

ABSTRACT The potential for DNA vaccines encoding mutated versions of the same antigen to modulate immune responses in C3H/HeN mice was investigated. We created expression plasmids that encoded several versions of glycoprotein D (gD) from bovine herpesvirus 1, including authentic membrane-anchored glycoprotein (pSLRSV.AgD), a secreted glycoprotein (pSLRSV.SgD), and an intracellular protein (pSLRSV.CgD). Immunization of an inbred strain of mice with these plasmids resulted in highly efficacious and long-lasting humoral and cell-mediated immunity. We also demonstrated that the cell compartment in which plasmid-encoded gD was expressed caused a deviation in the serum immunoglobulin (Ig) isotype profile as well as the predominant cytokines secreted from the draining lymph node. Immunization of C3H/HeN mice with DNA vaccines encoding cell-associated forms of gD resulted in a predominance of serum IgG2a and gamma interferon-secreting cells within the spleens and draining lymph nodes. In contrast, mice immunized with a secreted form of this same antigen displayed immune responses characterized by greater levels of interleukin 4 in the draining lymph node and IgG1 as the predominant serum isotype. We also showed evidence of compartmentalization of distinct immune responses within different lymphoid organs.

Nanodiamonds in Oil Emulsions as Effective Vaccine Adjuvants and Antitumor Therapeutic Agents

2021 ◽  
Author(s):  
Hsin-Hung Lin ◽  
Chih-Yen Wang ◽  
Feng-Jen Hsieh ◽  
Fang-Zhen Liao ◽  
Yu-Kai Su ◽  
...  
Keyword(s):  
Antibody Production ◽  
High Efficiency ◽  
Effective Vaccine ◽  
Vaccine Adjuvants ◽  
Immunological Responses ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Oil Emulsions ◽  
New Formulation ◽  
Therapeutic Activities

Abstract Background Vaccination is an effective tool to elicit immunological responses that mediate the protection from infection or disease. Composed of mineral oil and mycobacteria pathogens, complete Freund’s adjuvant (CFA) is one of the most commonly employed adjuvants for antibody production and vaccination due to its high efficiency. However, the dead mycobacteria in CFA can cause many allergic reactions. To avoid these adverse effects, we propose here a new formulation based on the use of nanodiamonds (NDs) as biocompatible non-allergic additives in incomplete Freund’s adjuvant (IFA) instead. ResultsTested with chicken egg ovalbumin (OVA) in mouse models, the new formulation with 100-nm NDs was found to serve well as a safe and potent vaccine adjuvant that significantly enhanced the immune responses and reduced the consumption of antigens in producing the antibodies of interest. Additionally, the composites showed distinct therapeutic activities, as proven by the OVA/ND/IFA treatment which effectively inhibited the tumor progression of OVA-expressing E.G7 cells inoculated in mice and allowed the animals to survive up to 35 days post tumor-cell challenges. ConclusionsThe dual functionality of ND/IFA makes it useful as adjuvants not only to increase antibody production but also to create single-dose vaccines.

scholarly journals The Virulence of Different Vaccinia Virus Strains Is Directly Proportional to Their Ability To Downmodulate Specific Cell-Mediated Immune CompartmentsIn Vivo

2018 ◽  
Vol 93 (6) ◽  
Author(s):  
Lorena F. D. de Freitas ◽  
Rafael P. Oliveira ◽  
Mariana C. G. Miranda ◽  
Raíssa P. Rocha ◽  
Edel F. Barbosa-Stancioli ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
Viral Vector ◽  
Smallpox Vaccination ◽  
Direct Result ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Cell Responses ◽  
Virus Strains

ABSTRACTVaccinia virus (VACV) is a notorious virus for a number of scientific reasons; however, most of its notoriety comes from the fact that it was used as a vaccine against smallpox, being ultimately responsible for the eradication of that disease. Nonetheless, many different vaccinia virus strains have been obtained over the years; some are suitable to be used as vaccines, whereas others are virulent and unsuitable for this purpose. Interestingly, different vaccinia virus strains elicit different immune responsesin vivo, and this is a direct result of the genomic differences among strains. In order to evaluate the net result of virus-encoded immune evasion strategies of vaccinia viruses, we compared antiviral immune responses in mice intranasally infected by the highly attenuated and nonreplicative MVA strain, the attenuated and replicative Lister strain, or the virulent WR strain. Overall, cell responses elicited upon WR infections are downmodulated compared to those elicited by MVA and Lister infections, especially in determined cell compartments such as macrophages/monocytes and CD4+T cells. CD4+T cells are not only diminished in WR-infected mice but also less activated, as evaluated by the expression of costimulatory molecules such as CD25, CD212, and CD28 and by the production of cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-10. On the other hand, MVA infections are able to induce strong T-cell responses in mice, whereas Lister infections consistently induced responses that were intermediary between those induced by WR and MVA. Together, our results support a model in which the virulence of a VACV strain is proportional to its potential to downmodulate the host’s immune responses.IMPORTANCEVaccinia virus was used as vaccine against smallpox and was instrumental in the successful eradication of that disease. Although smallpox vaccination is no longer in place in the overall population, the use of vaccinia virus in the development of viral vector-based vaccines has become popular. Nonetheless, different vaccinia virus strains are known and induce different immune responses. To look into this, we compared immune responses triggered by mouse infections with the nonreplicative MVA strain, the attenuated Lister strain, or the virulent WR strain. We observed that the WR strain was capable of downmodulating mouse cell responses, whereas the highly attenuated MVA strain induced high levels of cell-mediated immunity. Infections by the intermediately attenuated Lister strain induced cell responses that were intermediary between those induced by WR and MVA. We propose that the virulence of a vaccinia virus strain is directly proportional to its ability to downmodulate specific compartments of antiviral cell responses.

scholarly journals Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40745 ◽  
Author(s):  
Juliana Vitoriano-Souza ◽  
Nádia das Dores Moreira ◽  
Andréa Teixeira-Carvalho ◽  
Cláudia Martins Carneiro ◽  
Fernando Augusto Mathias Siqueira ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Adjuvants ◽  
Cell Recruitment ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Incomplete Freund’S Adjuvant ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

Cattle immune responses to tetanus toxoid elicited by recombinant S. typhimurium vaccines or tetanus toxoid in alum or Freund's adjuvant

Vaccine ◽  
2000 ◽  
Vol 18 (15) ◽  
pp. 1515-1521 ◽  
Author(s):  
Bernardo Villarreal-Ramos ◽  
Jaquie M. Manser ◽  
Robert A. Collins ◽  
Gordon Dougan ◽  
Christopher J. Howard
Keyword(s):  
Immune Responses ◽  
Tetanus Toxoid ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant

scholarly journals Adjuvant Immunotherapy Is Dependent on Inducible Nitric Oxide Synthase

2001 ◽  
Vol 193 (11) ◽  
pp. 1261-1268 ◽  
Author(s):  
Daniel A. Kahn ◽  
D. Clay Archer ◽  
Daniel P. Gold ◽  
Carolyn J. Kelly
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Immune Responses ◽  
Inducible Nitric Oxide Synthase ◽  
Interferon Γ ◽  
Type I ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Rodents immunized with complete Freund's adjuvant (CFA) are resistant to subsequent attempts to induce autoimmune disease, while animals immunized with incomplete Freund's adjuvant (IFA) remain susceptible. Mycobacterial extracts can stimulate inducible nitric oxide synthase (NOS2) gene transcription. Robust expression of NOS2 has been linked to suppression of T cell proliferation and alterations in immune responses. Our studies investigated the hypothesis that the immunoprotective effect of CFA before immunization requires functional NOS2. NOS2 gene expression is chronically elevated in lymph nodes and spleens of CFA-immunized mice. Maximal expression of NOS2 after CFA immunization requires the presence of functional type I tumor necrosis factor α receptor (TNFR1) and interferon γ. Groups of nontreated and CFA-preimmunized male C57BL/6J or C57BL/6NOS2−/− mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35–55 in CFA to induce experimental allergic encephalomyelitis (EAE). Wild-type C57BL/6J mice were protected from the development of symptoms of EAE, while the NOS2−/− mice failed to be protected. NOS2-dependent effects of CFA included an augmentation of the MOG-specific IgG1 response, a decrease in interleukin 6 production by MOG-reactive lymphocytes, and a marked decrease in mononuclear cell infiltrates in the central nervous system. These studies support the hypothesis that CFA immunization modulates immune responses through a nitric oxide–dependent mechanism.

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