CVD 909

CVD 909 is an attenuated live oral typhoid vaccine candidate derived from strain CVD 908-htrA. It was genetically modified to constitutively express Vi polysaccharide capsular antigen of Salmonella Typhi[1][3][7]. This vaccine candidate has been evaluated in clinical trials for its safety, immunogenicity, and ability to induce immune responses against typhoid fever. The vaccine works by eliciting a wide array of cell-mediated immune responses, including cytotoxic T cells, IFN-gamma, TNF-alpha, and IL-10 production, as well as proliferation to S. Typhi antigens[7]. It has been shown to induce opsonophagocytic functional antibodies that can cross-react with S. Paratyphi A and S. Paratyphi B, though with lower magnitudes[4]. Clinical trials have demonstrated that CVD 909 is well-tolerated and immunogenic. It has been tested in various dosing regimens, including as a single dose and in a heterologous prime-boost strategy with parenteral Vi vaccine[1][7]. The vaccine has shown promise as a potential single-dose live vaccine against S. Typhi[4]. ## Development Status CVD 909 has undergone Phase 1 clinical trials for typhoid fever prevention. One clinical trial (NCT00326443) evaluated its use in a heterologous prime-boost strategy with parenteral Vi vaccine[1]. The vaccine has shown immunogenicity comparable to four doses of Ty21a (another typhoid vaccine) after just a single dose[4]. There are also indications that CVD 909 might be considered for development as part of a bivalent vaccine (CVD 1902 + CVD 909) for broader protection against typhoid and paratyphoid fevers[8]. ## Immune Response CVD 909 induces both humoral and cell-mediated immune responses: - **Humoral immunity**: While it may not significantly increase serum anti-Vi antibodies on its own, it can prime for enhanced responses to subsequent Vi polysaccharide vaccination[1]. It also elicits anti-lipopolysaccharide antibodies and IgA antibody-secreting cells to Vi[3]. - **Cell-mediated immunity**: The vaccine induces a complex pattern of CD4+ memory T cells with the capability to home to the lamina propria and Peyer's patches[3]. It elicits cytotoxic T cells, IFN-gamma, TNF-alpha, and IL-10 production[7]. - **Cross-reactive immunity**: Functional antibodies induced by CVD 909 show cross-reactivity against S. Paratyphi A and S. Paratyphi B, suggesting potential cross-protection[4]. The genetic modifications to constitutively express Vi did not adversely affect the ability of CVD 909 to elicit a wide array of cell-mediated immune responses, making it a promising typhoid vaccine candidate[7].