Synthetic Toll-like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome.
(65/301)
The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure consisting of a hexa-acylated acyclic backbone. The vaccine examined is a recombinantly attenuated form of staphylococcal enterotoxin B (STEBVax). Using cells stably transfected with TLRs, E6020 transduced signals only through TLR4, suggesting monospecificity, while Escherichia coli 055:B5 lipopolysaccharide activated both the TLR2/6 heterodimer and TLR4. Coadministration of E6020 with STEBVax, by the intramuscular or intranasal route, induced significant levels of immunoglobulin G (IgG) in BALB/c mice. Further, increased IgG production resulted from the combination of E6020 with aluminum hydroxide adjuvant (AH). The antibody response to the vaccine coadministered with E6020 was a mixed Th1/Th2 response, as opposed to the Th2-biased response obtained with AH. Mice vaccinated with STEBVax coadministered with AH, TLR4 agonists, or a combination of both adjuvants were protected from toxic shock. Our data demonstrate the effectiveness of the synthetic TLR4 agonist E6020 as an alternative adjuvant for protein subunit vaccines that may also be used in combination with traditional aluminum-containing adjuvants. (+info)
Interleukin-15 increases vaccine efficacy through a mechanism linked to dendritic cell maturation and enhanced antibody titers.
(66/301)
Interleukin-15 (IL-15) is generally considered to sustain T-cell memory and to be a growth factor for natural killer cells. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. For this study, we investigated the effects of IL-15 on antibody responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax) in a preclinical model of toxic shock syndrome induced by SEB. We observed that mouse spleen cells treated with IL-15 in ex vivo culture gained a dendritic cell-like phenotype. Administration of IL-15 to mice also resulted in an increased number of mature CD11c+ dendritic cells in mouse spleens. A significant, IL-15 dose-dependent increase in antigen-specific antibody was observed after coadministration with the vaccine and an aluminum-based adjuvant (alhydrogel). Furthermore, the coadministration of IL-15 with STEBVax and alhydrogel also protected mice from lethal toxic shock above the levels that obtained without IL-15. Thus, the vaccine response enhanced by IL-15 appears to be mediated by mature dendritic cells and results in prevalent seroconversion to Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines. (+info)
Ginsenoside Rg1 and aluminum hydroxide synergistically promote immune responses to ovalbumin in BALB/c mice.
(67/301)
The combined adjuvant effect of ginsenoside Rg1 and aluminum hydroxide (alum) on immune responses to ovalbumin (OVA) in mice was investigated. BALB/c mice were subcutaneously (s.c.) inoculated twice with OVA alone or in combination with Rg1, alum, or Rg1 plus alum. Samples were collected 2 weeks after the boosting for the measurement of anti-OVA immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-gamma) and interleukin-5 (IL-5) produced in singular splenocyte cultures. Delayed-type hypersensitivity (DTH) responses were measured in mice immunized as described above. After 10 days, the mice were injected s.c. with OVA at the footpads. Thereafter, the thickness of the footpads was measured once daily for 5 days. The results indicated that alum enhanced mainly Th2 (IgG1 and IL-5) responses (P < 0.05), while Rg1 enhanced both Th1 (IgG1 and IL-5) and Th2 (IgG2a, IFN-gamma, and DTH) responses (P < 0.05). The highest immune responses were found in the mice injected with OVA solution containing both alum and Rg1. In addition, the hemolytic activity of Rg1 was much lower than that of Quil A. Therefore, Rg1 deserves further studies in order to tailor desired immune responses when a mixed Th1/Th2 immune response is needed. (+info)
Considerable differences in vaccine immunogenicities and efficacies related to the diluent used for aluminum hydroxide adjuvant.
(68/301)
Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein.
(69/301)
Immunogenicity of a thermally inactivated rotavirus vaccine in mice.
(72/301)
Current approaches to the prevention of severe rotavirus diarrhea and deaths in children have all been through the use of live oral vaccines. To develop a safe and effective inactivated rotavirus vaccine (IRV), a new simple, rapid and robust method for the inactivation is critical and essential because chemical inactivation commonly used for a number of killed vaccines has been a challenge and problematic for rotavirus. We have examined an array of thermal conditions and demonstrated that purified YK-1 rotavirus in diluent buffer can be completely inactivated by heat treatment, as evidenced by the lack of virus growth in two successive passages in cell culture. Unlike chemical treatment that often causes physical and biochemical damages to viruses, thermally inactivated rotavirus particles maintained their structural, biochemical and antigenic integrity. A two-dose intramuscular administration of thermally inactivated YK-1 rotavirus without adjuvant resulted in high titers of total and neutralizing antibody in serum of mice. Adjuvant Al(OH)(3) further led to enhanced antibody titers and also dramatically lowered the amount of antigens in the vaccine formulation. Our results demonstrate the potential of heat inactivation as a novel approach to the manufacture of a safe and efficacious parenteral rotavirus vaccine, which should serve as an important addition to and back up for live oral rotavirus vaccine in children. (+info)