Macrolidic antibiotics: Effects on primary in vitro antibody responses

Abstract Neutrophils can shape adaptive immunity; however, their role in vaccine-induced protection against infections in vivo remains unclear. Here, we tested their role in the clinically relevant polysaccharide conjugate vaccine against Streptococcus pneumoniae (pneumococcus). We antibody depleted neutrophils during vaccination, allowed them to recover, and 4 weeks later challenged mice with pneumococci. We found that while isotype-treated vaccinated controls were protected against an otherwise lethal infection in naive mice, full protection was lost upon neutrophil depletion. Compared to vaccinated controls, neutrophil-depleted mice had higher lung bacterial burdens, increased incidence of bacteremia, and lower survival rates. Sera from neutrophil-depleted mice had less antipneumococcal IgG2c and IgG3, were less efficient at inducing opsonophagocytic killing of bacteria by neutrophils in vitro, and were worse at protecting naive mice against pneumococcal pneumonia. In summary, neutrophils are required during vaccination for optimal host protection, which has important implications for future vaccine design against pneumococci and other pathogens.

Download Full-text

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

npj Vaccines ◽

10.1038/s41541-020-00229-9 ◽

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.

Download Full-text

Antibody responses of experimentally infected lambs to antigens collected during in vitro maintenance of the adult, metacestode or oncosphere stages ofTaenia hydatigena andTaenia ovis with further observations on anti-oncospheral antibodies

Zeitschrift für Parasitenkunde Parasitology Research ◽

10.1007/bf00928115 ◽

1982 ◽

Vol 67 (2) ◽

pp. 197-209 ◽

Cited By ~ 12

Author(s):

P. S. Craig ◽

M. D. Rickard

Keyword(s):

Antibody Responses ◽

In Vitro Maintenance

Download Full-text

Enhancement of in vitro and in vivo antigen-specific antibody responses by interleukin 11.

Journal of Experimental Medicine ◽

10.1084/jem.175.1.211 ◽

1992 ◽

Vol 175 (1) ◽

pp. 211-216 ◽

Cited By ~ 75

Author(s):

T G Yin ◽

P Schendel ◽

Y C Yang

Keyword(s):

T Cells ◽

Antibody Titer ◽

Specific Antibody ◽

Antibody Responses ◽

Rabbit Serum ◽

Dependent Manner ◽

Dose Dependent ◽

Interleukin 11

The availability of large quantities of highly purified recombinant interleukin 11 (rhuIL-11) has allowed us to investigate the effects of rhuIL-11 on sheep red blood cell (SRBC)-specific antibody responses in the murine system. The results showed that rhuIL-11 was effective in enhancing the generation of mouse spleen SRBC-specific plaque-forming cells (PFC) in the in vitro cell culture system in a dose-dependent manner. These effects of rhuIL-11 were abrogated completely by the addition of anti-rhuIL-11 antibody, but not by the addition of preimmunized rabbit serum. Cell-depletion studies revealed that L3T4 (CD4)+ T cells, but not Lyt-2 (CD8)+ T cells, are required in the rhuIL-11-stimulated augmentation of SRBC-specific antibody responses. The effects of rhuIL-11 on the SRBC-specific antibody responses in vivo were also examined. RhuIL-11 administration to normal C3H/HeJ mice resulted in a dose-dependent increase in the number of spleen SRBC-specific PFC as well as serum SRBC-specific antibody titer in both the primary and secondary immune responses. In mice immunosuppressed by cyclophosphamide treatment, rhuIL-11 administration significantly augmented the number of spleen SRBC-specific PFC as well as serum SRBC-specific antibody titer when compared with the cyclophosphamide-treated mice without IL-11 treatment. These results demonstrated that IL-11 is a novel cytokine involved in modulating antigen-specific antibody responses in vitro as well as in vivo.

Download Full-text

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

Journal of Experimental Medicine ◽

10.1084/jem.154.1.35 ◽

1981 ◽

Vol 154 (1) ◽

pp. 35-47 ◽

Cited By ~ 5

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.

Download Full-text

Recombinant Antigen-Enterotoxin A2/B Chimeric Mucosal Immunogens Differentially Enhance Antibody Responses and B7-Dependent Costimulation of CD4+ T Cells

Infection and Immunity ◽

10.1128/iai.69.1.252-261.2001 ◽

2001 ◽

Vol 69 (1) ◽

pp. 252-261 ◽

Cited By ~ 25

Author(s):

Michael Martin ◽

George Hajishengallis ◽

Daniel J. Metzger ◽

Suzanne M. Michalek ◽

Terry D. Connell ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Ex Vivo ◽

Immunoglobulin A ◽

Chimeric Protein ◽

Antibody Responses ◽

Chimeric Proteins ◽

Binding Region ◽

Cervical Lymph Nodes

ABSTRACT The ADP-ribosylating enterotoxins, cholera toxin (CT) and theEscherichia coli heat-labile toxin (LT-IIa), have been shown to enhance mucosal and systemic antibody (Ab) responses to coadministered antigens. The purpose of the present study was to compare the ability of the nontoxic A2/B subunits of these toxins, which have distinct targeting properties, to augment the immunogenicity of a genetically coupled protein antigen. Structurally similar chimeric proteins were generated by genetically replacing the toxic A1 subunit of CT or LT-IIa with the saliva-binding region (SBR) from the streptococcal adhesin AgI/II. Intranasal immunization of BALB/c mice with either chimeric protein induced significantly higher plasma and mucosal anti-SBR immunoglobulin A (IgA) and IgG Ab responses than SBR alone. Moreover, compared to SBR–LT-IIaA2/B, SBR-CTA2/B elicited significantly higher levels of plasma IgG1 and salivary IgA anti-SBR Ab responses. Ex vivo and in vitro experiments revealed that SBR-CTA2/B selectively up-regulated B7-2 expression on murine B cells isolated from both the nasal associated lymphoid tissue, cervical lymph nodes, and spleen. In contrast, SBR–LT-IIaA2/B had little effect on B7-1 or B7-2 expression on B220+, CD11b+, or CD11c+ cells. Analysis of the functional costimulatory activity of SBR-CTA2/B-treated B cells revealed a significant enhancement in anti-CD3-stimulated CD4+ T-cell proliferative responses, and this proliferation was significantly reduced by treatment with anti-B7-2 but not with anti-B7-1 or isotype control Abs. Thus, SBR-CTA2/B and SBR–LT-IIaA2/B exhibit distinct patterns of antibody responses associated with differential effects on B7-2 expression and subsequent costimulatory effects on CD4+ T cells.

Download Full-text