Anthrax vaccines

About: Anthrax vaccines is a research topic. Over the lifetime, 685 publications have been published within this topic receiving 21495 citations.

Toll-like receptor 4 signalling regulates antibody response to adenoviral vector-based vaccines by imprinting germinal centre quality.

Abstract: Adenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of Toll-like receptors (TLRs) participate in the adenovirus-induced adaptive immune response, yet there is little information regarding the role of TLR4 in AdV-induced immune responses in recent literature. We investigated the function of TLR4 in both adaptive and innate immune responses to an AdV-based anthrax vaccine. By immunizing wild-type and TLR4 knockout (TLR4-KO) mice, we revealed the requirement of TLR4 in AdV-induced innate responses. We also showed that TLR4 functions are required for germinal centre responses in immunized mice, as expression of the apoptosis-related marker Fas was down-regulated on germinal centre B cells from TLR4-KO mice. Likewise, decreased expression of inducible costimulator on follicular T helper cells was observed in immunized TLR4-KO mice. Moreover, a potent protective antigen-specific humoral immune response was mimicked using an adjuvant system containing the TLR4 agonist monophosphoryl lipid A. Overall, our findings showed that very rapid antigen-specific antibody production is correlated with the TLR4-imprinted germinal centre response to AdV-based vaccine. These results provide additional evidence for the use of the AdV and a TLR agonist to induce humoral responses. Our findings offer new insights into rational vaccine design.

Enhanced systemic and mucosal immune responses in mice immunized with recombinant Bacillus anthracis protective antigen (rPA) using a novel nanoemulsion adjuvant

Abstract: Rationale New anthrax vaccines involve immunization with rPA, an immunologic target of antibodies that neutralize anthrax toxin. We have evaluated a non-toxic nanoemulsion as an adjuvant for intramuscular (IM) and intranasal (IN) immunization with rPA. Methods Balb/c mice were immunized with three monthly administrations of 2.5 and 25 ug rPA. The protein was given alone, in a solution of 1% nanoemulsion or with the nanoemulsion and CpG-rich oligonucleotides. Results IM injections of rPA with nanoemulsion resulted in higher titers of anti-PA IgG than IM administration of antigen alone, particularly with low doses of rPA. In contrast, nanoemulsion was absolutely required for the development of immunity after IN administration since anti-PA specific IgA (in bronchial lavage) and IgG (in serum) were observed only in animals receiving in rPA with nanoemulsion, whether or not CpG was present. No animal immunized IM with rPA developed a mucosal antibody response. rPA specific splenocyte activation was demonstrated by proliferative responses in vitro and was accompanied by markedly increased production of INFγ and TNFα, indicating that TH1 responses were induced by the nanoemulsion. Nanoemulsion increased in vitro binding of rPA to dendritic cells but not lymphocytes, suggesting dendritic cells participate in the induction of rPA mucosal immunity after IN immunization. Conclusions Nanoemulsions may serve as useful adjuvants for recombinant anthrax vaccines.

Natural cutaneous anthrax infection, but not vaccination, induces a CD4+ T cell response involving diverse cytokines

Abstract: Background Whilst there have been a number of insights into the subsets of CD4+ T cells induced by pathogenic Bacillus anthracis infections in animal models, how these findings relate to responses generated in naturally infected and vaccinated humans has yet to be fully established. We describe the cytokine profile produced in response to T cell stimulation with a previously defined immunodominant antigen of anthrax, lethal factor (LF), domain IV, in cohorts of individuals with a history of cutaneous anthrax, compared with vaccinees receiving the U.K. licenced Anthrax Vaccine Precipitated (AVP) vaccine.