Enhancement of the immune responses of mice to Bacillus anthracis protective antigen by CIA07 combined with alum

Abstract

Anthrax is an acute zoonotic disease caused by infection with Bacillus anthracis. B. anthracis spores are highly resistant to environmental degradation and are used as a biological weapon. In this study, we investigated the adjuvant activity of CIA07 to anthrax protective antigen (PA). A/J mice were immunized intraperitoneally once, or twice with a 4-week interval, with recombinant PA alone or combined with alum, CpG1826, or CIA07 as adjuvant, and serum anti-PA IgG antibody responses were measured 4 weeks after each immunization. All three adjuvants significantly enhanced anti-PA IgG antibody titer 4 weeks after the priming and boosting immunizations, and alum gave the highest titer. In order to evaluate the adjuvant activity of CIA07 in the presence of alum, Balb/c mice were immunized 3 times at 1-week intervals with PA in combination with alum, CIA07 or alum plus CIA07, and the immune responses were assessed 2 weeks after the third immunization. The serum anti-PA IgG antibody titer of the CIA07-treated group was 14-fold higher than the group given PA alone, and the coadministration of CIA07 with alum further increased the titer 3.5-fold (P < 0.05). The toxin neutralizing activity of the sera from the mice given the combination of CIA07 and alum was 109-times higher than the animals given PA alone. The mice given CIA07 plus alum also showed a marked increase in the number of IFN-gamma-, IL-2-, and IL-4-producing CD4(+) T cells among their splenocytes. These data suggest the potential of CIA07 in combination with alum as an adjuvant for the development of a potent anthrax vaccine.

A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice

“…In addition, we observed that addition of CIA05 to a human papilloma virus (HPV) vaccine adjuvanted with alum significantly enhanced the immunogenicity of the vaccine antigen, demonstrating the synergistic activity of CIA05 and alum in the enhancement of immune responses to a vaccine antigen [18]. In a previous study, we evaluated an adjuvant effect of CIA07 to PA and observed that CIA07 alone was not as effective as alum in inducing PA-specific antibody but gave an additive effect only when combined with alum [19]. This study was carried out to evaluate the potential of CIA05 combined with alum as an adjuvant for an anthrax vaccine and to determine an optimal ratio between PA antigen, CIA05, and alum.…”

Progress and novel strategies in vaccine development and treatment of anthrax

“…Polyoxyethylene-polyoxypropylene (POE-POP) and immunostimulatory DNA containing CpG domains, seemed to be good potentiators of PA immunogenicity in mice (111) and rhesus macaques (112). Similarly, Alum and CIA07 (a combination of bacterial DNA fragments and modified E. coli lipopolysaccharide containing a short carbohydrate chain) appeared to be superior in terms of their immunostimulatory activity, compared with each adjuvant alone, when tested in mice for PA immunization potentiation (113). The mast cell activator compound 48 ⁄ 80 also was suggested to be an efficient inducer of an anti-PA antibody responses in mice (114).…”

Anthrax Vaccines

“…Some of these CpG motif ODNs have been evaluated in human clinical trials, thus providing a level of confi dence in their safety and effi cacy if used in human vaccines (Klinman, 2006 ). The presence of all three anthrax toxin components PA, LF, and EF in a polyvalent vaccine formulation also enhances antibody responses to all three components Kelly et al, 2007 ;Kim et al, 2008 ;Kolla et al, 2007 ;McLachlan et al, 2008 ;Park et al, 2008 ;Pezard et al, 1995 ;Quesnel -Hellmann et al, 2006 ;Sloat and Cui, 2006 ). These studies confi rm the pivotal role of PA in protection and that effi cacy can be enhanced by considered formulation, and serve as timely reminders that design of anthrax vaccines should be based fi rmly on the host in which the vaccine will eventually be used.…”

“…This research has included analyses of PA polypeptide domains (Flick -Smith et al, 2002b ;Yan et al, 2008 ), DNA vaccines (Galloway and Baillie, 2004 ), alternative delivery technologies (Luxembourg et al, 2008 ;Mikszta et al, 2005 ), evaluation of novel adjuvants (Kelly et al, 2007 ;Kim et al, 2008 ;Park et al, 2008 ), oral and mucosal vaccines Baillie et al, 2008 ;Bielinska et al, 2007 ;Jiang et al, 2006 ;Stokes et al, 2007 ), and PA -producing liveattenuated vaccines (Ivins et al, 1990 ;Skoble et al, 2009 ).…”