OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis

• Published in: Vaccine 2014-10, Vol.32 (45), p.5918-5924
• Main Authors: Yanase, Noriko, Toyota, Hiroko, Hata, Kikumi, Yagyu, Seina, Seki, Takahiro, Harada, Mitsunori, Kato, Yasuki, Mizuguchi, Junichiro
• Format: Article
• Language: English
• Subjects: Adjuvants; Adjuvants, Immunologic - pharmacology; Allergy and Immunology; Alum Compounds - pharmacology; Animals; Antibody Formation; Antibody responses; Antigens; Applied microbiology; B-Lymphocytes - immunology; Biological and medical sciences; Cytokines; Cytokines - immunology; Drug dosages; Formulation; Fundamental and applied biological sciences. Psychology; Immune system; Immunization; Immunoglobulin E - biosynthesis; Immunoglobulin G - immunology; Immunology; Mice, Inbred BALB C; Microbiology; Nanoparticles; Nanoparticles - administration & dosage; Ovalbumin - pharmacology; Phosphatase; Polyethylene glycol; Th1 Cells - immunology; Th2 Cells - immunology; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2014.08.059

Abstract There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110 nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses ( i.e. , Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro , OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis.