Oligonucleotides containing CpG motifs (CpG ODN) are strong adjuvants for humoral immune responses but data on cellular immune responses in primates are scarce. Rhesus macaque blood contained similar numbers of plasmacytoid dendritic cells and B cells, the key sensors of CpG ODN, as human blood, and these cells were activated by CpG-A and CpG-B in vitro. In vivo, both ODNs induced equal plasma levels of interferon-inducible protein 10 and similarly enhanced antibody responses following i.m. injections of the ODNs, protein antigen, and aluminium hydroxide into rhesus macaques, whereas antigen-specific CD4(+) T cell responses were only slightly increased by CpG ODN.
"The cell surface and intracellular cytokine staining was evaluated using flow cytometry (31,32). Briefly, cell suspensions from immunized mice were harvested from the spleen as described previously, then splenocytes were aliquoted into six-well round-bottom plates at 1×106 cells/well and stimulated with 10 μg/ml OVA in the presence of 5 μM brefeldin A (10 μg/ml; Sigma) for 24 h. "
[Show abstract][Hide abstract] ABSTRACT: In the present study, a low molecular weight polysaccharide, ABP-AW1, isolated from Agaricus blazei Murill was assessed for its potential adjuvant activity. ABP-AW1 is considered to create a 'depot' of antigen at a subcutaneous injection site. ICR mice were immunized with 100 μg ovalbumin (OVA) alone or with 100 μg OVA formulated in 0.9% saline containing 200 μg aluminum (alum) or ABP-AW1 (50, 100 and 200 μg) on days 1 and 15. Two weeks after the secondary immunization, splenocyte proliferation, the expression of surface markers, cytokine production and the OVA-specific antibody levels in the serum were determined. The OVA/ABP-AW1 vaccine, in comparison with OVA alone, markedly increased the proliferation of splenic lymphocytes and elicited greater antigen-specific CD4(+) T cell activation, as determined by splenic CD4(+)CD69(+) T cells and Th1 cytokine interferon (IFN)-γ release. The combination of ABP-AW1 and OVA also enhanced IgG2b antibody responses to OVA. In conclusion, these data indicated that ABP-AW1 significantly enhanced the humoral and cellular immune responses against OVA in the mice, suggesting that ABP-AW1 stimulated Th1-type immunity. We suggest that ABP-AW1 may serve as a new adjuvant.
[Show abstract][Hide abstract] ABSTRACT: The goal for an effective malaria transmission-blocking vaccine (TBV) is to induce immunity against the stages of the parasite that infect mosquitoes so that malaria transmission can be reduced or halted. Malaria transmission is generally spatially confined to an infectious source, thus a TBV used in a community can effectively suppress malaria transmission to others. Antibodies induced by TBVs target antigens on the surface of sexual and mosquito midgut stages of the malaria parasite and antibodies interfere with the development of the parasites in the midgut of the mosquito. Proteins synthesized in the gametocytes (pre-fertilization antigens, in Plasmodium falciparum: Pfs230 and Pfs48/45) and in the zygotes-ookinetes (post-fertilization antigens, in P. falciparum: Pfs25 and Pfs28) represent some of the key target antigens for the development of TBVs. All the four proteins contain multiple cysteinerich sequences and the epitopes recognized by transmission-blocking antibodies are reduction-sensitive conformational in nature. The inability to express properly folded proteins has frustrated a protein-based TBV development approach and DNA-based vaccine constructs were envisaged to overcome the conformational problem in recombinant proteins. Indeed studies in mice and monkeys have firmly established the value of DNA-based TBV approach. Although immunogenic in larger animals, delivery of DNA-based TBVs needs to be further optimized to elicit a strong and long lasting functional immune response. This DNA vaccine platform can also facilitate evaluation of a cocktail of pre- and post-fertilization antigens in pre-clinical setting prior to the development of an ideal and effective TBV for clinical trials in human volunteers.
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