scholarly journals Efficiency of pH-Sensitive Fusogenic Polymer-Modified Liposomes as a Vaccine Carrier

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shinobu Watarai ◽  
Tana Iwase ◽  
Tomoko Tajima ◽  
Eiji Yuba ◽  
Kenji Kono
Keyword(s):  
Immune Responses ◽  
Ph Sensitive ◽  
Antibody Responses ◽  
Antigen Delivery ◽  
Spleen Cells ◽  
Delivery Vehicle ◽  
Spleen Lymphocytes ◽  
Vaccine Carrier ◽  
Specific Mrna

The usefulness of pH-sensitive fusogenic polymer-(succinylated poly(glycidol)-(SucPG-) modified liposomes as a vaccine carrier in the induction of immune responses was evaluated. Mice were intraperitoneally immunized with ovalbumin- (OVA-) containing SucPG-modified liposomes. After immunization, significant OVA-specific antibodies were detected in the serum. When sera were analyzed for isotype distribution, OVA-specific IgG1 antibody responses were noted in mice immunized with OVA-containing polymer-unmodified liposomes, whereas immunization with OVA-containing SucPG-modified liposomes resulted in the induction of OVA-specific IgG1, IgG2a, and IgG3 Ab responses. In spleen lymphocytes from mice immunized with OVA-containing SucPG-modified liposomes, both IFN-γ-(Th1-type-) and IL-4-(Th2 type-) specific mRNA were detected. Moreover, substantial production of IFN-γand IL-4 was demonstrated in spleen cells from OVA-containing SucPG-modified liposomesin vitro. These results suggest that the pH-sensitive fusogenic polymer-(SucPG-) modified liposomes would serve effectively as an antigen delivery vehicle for inducing Th1 and Th2 immune responses.

scholarly journals IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (4) ◽  
pp. 921-938 ◽  
Author(s):  
Carl W. Pierce ◽  
Judith A. Kapp ◽  
Susan M. Solliday ◽  
Martin E. Dorf ◽  
Baruj Benacerraf
Keyword(s):  
Immune Responses ◽  
Lymphoid Cells ◽  
Antibody Responses ◽  
Current Understanding ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Selective Suppression ◽  
D Region ◽  
Stimulate Antibody

The effects of alloantisera against leukocyte alloantigens on plaque-forming cell (PFC) responses to sheep erythrocytes and the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by mouse spleen cells in vitro have been investigated. Polyspecific antibodies against both H-2 and non-H-2 alloantigens on responding spleen cells suppressed both IgM and IgG PFC responses; antisera against alloantigens coded for by the K and I regions, but not the D region, of the H-2 complex also effectively suppressed PFC responses. The suppression was not due to cytotoxicity to the spleen cells or anti-immunoglobulin activity in the sera and was directly related to the amount of antiserum added to the cultures. The suppression was specific for spleen cells against which the alloantiserum was directed. The alloantisera suppressed responses most effectively when present during the first 24 h of incubation, and although not rendering lymphoid cells incapable of developing PFC responses after removal of noncell-bound antibody, did act by interfering with successful initiation of the PFC response. The alloantisera suppressed both IgM and IgG PFC responses when directed against alloantigens only on macrophages, but selectively suppressed IgG responses when directed against alloantigens only on lymphoid cells. The alloantisera did not interfere with the ability of macrophages to bind GAT or to support the viability of the lymphoid cells, but did interfere with the ability of macrophage-associated antigen to effectively stimulate antibody responses by the lymphoid cells. Possible mechanisms for the effects of alloantisera on macrophages and the selective suppression of IgG responses when the antisera are directed against alloantigens on lymphoid cells are discussed with reference to our current understanding of genetic restrictions governing cell interactions in the development of antibody responses in mice.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (1) ◽  
pp. 185-198 ◽  
Author(s):  
Baruj Benacerraf ◽  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
David H. Katz
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Responses ◽  
Antibody Responses ◽  
Specific Response ◽  
Gene Products ◽  
Spleen Cells ◽  
Culture Initiation ◽  
Cooperative Interactions

The conditions for cooperative interactions between nonresponder B10.S B cells and GAT-primed irradiated (C57BL/6 x SJL)F1 T cells in the response by cultures of mouse spleen cells to GAT were investigated. GAT-specific antibody responses could be elicited by soluble GAT in cultures of GAT-primed irradiated (C57BL/6 x SJL)F1 T cells with C57BL/6 B cells but not with B10.S B cells. In contrast, when GAT was presented to the cultures on F1 macrophages or as aggregates of GAT with MBSA, GAT-specific PFC responses were observed with both B10.S or C57BL/6 B cells. Irradiated GAT-primed T cells were nevertheless essential for the development of these responses. The GAT-specific response of B10.S B cells in these cultures was inhibited by the addition of soluble GAT at culture initiation. These results indicate that genetic disparity at Ir loci is not an absolute barrier to T-B-cell cooperative interactions in the response to antigens under Ir gene control. The significance of these data for the function of Ir gene products in immunocompetent cells is discussed.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

scholarly journals Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Daniel Tapia ◽  
Javier I. Sanchez-Villamil ◽  
Alfredo G. Torres
Keyword(s):  
Rational Design ◽  
Antibody Responses ◽  
Effective Vaccine ◽  
Antigen Delivery ◽  
Burkholderia Mallei ◽  
Protein Antigens ◽  
Intrinsic Resistance ◽  
Vaccine Platform ◽  
A Genome

Abstract Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.

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.

scholarly journals Haplotype-specific suppression of antibody responses in vitro. I. Generation of genetically restricted suppressor T cells by neonatal treatment with semiallogeneic spleen cells

1981 ◽  
Vol 154 (1) ◽  
pp. 35-47 ◽  
Author(s):  
CM Sorensen ◽  
CW Pierce
Keyword(s):  
T Cells ◽  
Time Course ◽  
Antibody Responses ◽  
Primary Antibody ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Cytotoxic Lymphocyte ◽  
Necessary And Sufficient ◽  
Lymphocyte Responses

C57BL/10 mice were injected with semiallogeneic (B10.D2 X C57BL/10)F(1) spleen cells via the anterior facial vein within 24 h of birth to induce tolerance to B10.D2 (H-2(d)) alloantigens. Spleen cells from these mice as adults developed reduced, but significant, mixed lymphocyte and cytotoxic lymphocyte responses in vitro to H-2(d) stimulator cells and these treated mice rejected first-set B10.D2 skin grafts within a normal time-course, indicating that at best only a state of partial tolerance had been induced. Spleen cells from these mice failed to develop antibody responses to a variety of antigens in vitro when H-2(d) macrophages were in the cultures. Partially purified T cells from these neonatally treated mice suppressed primary antibody responses by normal syngeneic spleen cells in the presence of H-2(d) but not other allogeneic macrophages. These radiosensitive, haplotype-specific suppressor T (Ts) cells inhibited primary antibody responses by blocking initiation of the response, but failed to suppress secondary antibody responses and mixed lymphocyte or cytotoxic lymphocyte responses by appropriate responding spleen cells. To activate H-2(d) haplotype-specific Ts cells, stimulation with IA(d) subregion antigen(s) was necessary and sufficient; syngenicity at the I-A subregion of H-2 between the activated Ts cells and target responding spleen cell populations was also necessary and sufficient to achieve suppression. Comparable results have been obtained with spleen cells from BALB/c mice injected as neonates with (B10.D2 × C57BL/10)F(1) spleen cells where IA(b) antigens activate the haplotype-specific Ts cells. Implications for the significance of this population of haplotype-specific Ts cells in immune regulation are discussed and the properties of these Ts cells are compared and contrasted with other antigen-specific and nonspecific Ts cells whose activity is restricted by I- region products.

scholarly journals Antigen-specific suppressor T-cell activity in genetically restricted immune spleen cells.

1978 ◽  
Vol 148 (5) ◽  
pp. 1271-1281 ◽  
Author(s):  
C W Pierce ◽  
J A Kapp
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Activity ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Specific Suppressor T Cells ◽  
Immune Spleen Cells

Virgin spleen cells develop comparable primary antibody responses in vitro to syngeneic or allogeneic macrophages (Mphi) bearing the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), whereas immune spleen cells primed with syngeneic or allogeneic GAT-Mphi develop secondary responses preferentially when stimulated with GAT-Mphi syngeneic to the GAT-Mphi used for priming in vivo. These restrictions are mediated by products of the I-A subregion of the H-2 complex and are operative at the level of the GAT-Mphi-immune helper T-cell interactions. To investigate why these immune spleen cells fail to develop a significant antibody response to GAT-Mphi other than those used for in vivo immunization and determine the mechanism by which the restriction is maintained, spleen cells from virgin and syngeneic or allogeneic GAT-Mphi-primed mice were co-cultured in the presence of GAT-Mphi of various haplotypes. Antibody responses to GAT developed only in the presence of GAT-Mphi syngeneic to the Mphi used for in vivo priming; responses in cultures with GAT-Mphi allogeneic to the priming Mphi, whether these Mphi were syngeneic or allogeneic with respect to the responding spleen cells, were suppressed. The suppression was mediated by GAT-specific radiosensitive T cells. Thus, development of GAT-specific suppressor T cells appears to be a natural consequence of the immune response to GAT in responder as well as nonresponder mice. The implications of stimulation of genetically restricted immune helper T cells, and antigen-specific, but unrestricted, suppressor T cells after immunization with GAT-Mphi in vivo are discussed in the context of regulatory mechanisms in antibody responses.

scholarly journals CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO

1972 ◽  
Vol 135 (5) ◽  
pp. 1049-1058 ◽  
Author(s):  
Marc Feldmann
Keyword(s):  
Thoracic Duct ◽  
Glass Bead ◽  
Gamma Globulin ◽  
Antibody Responses ◽  
Cell Populations ◽  
Spleen Cells ◽  
Cooperative Response ◽  
Exact Function ◽  
Immune Response In Vitro

The requirement for macrophages in thymus-dependent antibody responses was studied in vitro. Three different macrophage-deficient cell populations were studied: spleen cells passed through a glass bead column at 37°C, spleen cells cultured with specific antimacrophage serum, and thoracic duct lymphocytes. These cell populations from mice primed to dinitrophenylated (DNP) fowl gamma globulin were unable to respond to the homologous conjugate in vitro. DNP-reactive B cells were present in normal proportions, since all three macrophage-depleted populations responded normally to macrophage-independent and thymus-independent DNP flagella. Carrier-reactive T cells were present, as the helper capacity of carrier-primed spleen cells was the same as carrier-primed lymphocytes, and thoracic duct lymphocytes are a well-established source of helper cells. The inhibition of the cooperative response was thus due to removal of macrophages, and this was proven by restoration of thymus-dependent anti-DNP responses by small numbers of anti-θ-treated peritoneal exudate cells. These results suggest that macrophages are essential in cell collaboration, While their exact function in cell collaboration is not yet known, the above observation suggests that the mechanism of T-B collaboration involves the surface of macrophages.

Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae

Parasitology ◽  
2000 ◽  
Vol 120 (3) ◽  
pp. 271-280 ◽  
Author(s):  
L. LE GOFF ◽  
C. MARTIN ◽  
I. P. OSWALD ◽  
P. N. VUONG ◽  
G. PETIT ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recovery Rate ◽  
Spleen Cells ◽  
Challenge Inoculation ◽  
Infective Larvae ◽  
Litomosoides Sigmodontis ◽  
Before And After ◽  
Type Response

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells.

1975 ◽  
Vol 142 (6) ◽  
pp. 1391-1402 ◽  
Author(s):  
S S Rich ◽  
R R Rich
Keyword(s):  
Immune Responses ◽  
Mixed Lymphocyte Reaction ◽  
Antigenic Specificity ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Homology Relationship ◽  
Cell Suppression ◽  
Mixed Lymphocyte Reactions

The mechanism of alloantigen-activated spleen cell suppression of mixed lymphocyte reaction (MLR) is explored in this report. Activated murine suppressor spleen cells elaborated a soluble noncytotoxic factor which suppressed MLR responses by 55-95%. Generation of suppressor factor required both in vivo alloantigen sensitization and specific in vitro restimulation. Suppressor factor was not produced by activated spleen cells which had been treated with anti-Thy-1.2 serum and complement. Antigenic specificity toward alloantigens of the stimulator cells was not demonstrable. In contrast, suppressor factor effectively inhibited MLR response only of responder cells of those strains that shared the D-end and the I-C subregion of the H-2 complex with the cells producing suppressor factor. Therefore, active suppression appears to require an MHC-directed homology relationship between regulating and responder cells in MLR.

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