Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection

Abstract

Candida albicans (CA) is a kind of fungi that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with Secreted aspartyl proteinases 2 (Sap2) could prevent the infection, we propose to use filamentous phage, a human-safe virus nanofiber specifically infecting bacteria (~900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val-Lys-Tyr-Thr-Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increase the survival rate of CA-infected mice. All these results, along with the fact that the virus nanofibers can be mass-produced by infecting bacteria cost-effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection.

Phage display as a tool for vaccine and immunotherapy development

“…59 The GALT samples circulating antigens mainly through microfold In another study aimed at infections of the mucosal tract, filamentous phage was used as an immunization strategy against CA. 60 This fungus is especially dangerous to patients with comprised immune systems, where it has a high morbidity and mortality rate. 61 Secretory aspartyl proteinases (Saps) are considered the major antigenic determinant in CA infection, with Sap2 being the most prominent to cause virulence.…”

Phage‐Enabled Nanomedicine: From Probes to Therapeutics in Precision Medicine

“…This approach led to curing of the infection as evidenced by significantly lowered fungal loading in the kidneys (i′). [140] …”

“…SAP2 is the most abundant of these SAPs.T herefore,aphage-based vaccine was created by displaying as hort peptide epitope from this target. [140] Filamentous fd phages displaying the epitope (the peptide Va l-Lys-Tyr-Thr-Ser) were shown to produce astrong immune response in mice.P hage-immunized mice showed dramatically increased survival after exposure to/infection with Candida albicans compared to non-immunized mice. Therefore,t his phage-based vaccine holds great promise for further clinical trials in humans.…”

“…This approach led to curing of the infectiona s evidenced by significantlyl owered fungal loading in the kidneys (i'). [140] Angewandte Chemie Reviews 10. Phage Structure Mimetics and Phage-Derived Particle Variants…”

Exploiting new knowledge of Candidal infection for future antifungal combat

“…Intravaginal immunization with truncated recombinant Sap2 showed prevention of C. albicans vaginal infection in a rat vaginal candidosis model as anti‐Sap2 antibodies were induced (Sandini et al , ). Intraperitoneally injected vaccine, where Sap2 epitopes were conjugated with nanofibers, showed reduced Candida load and higher survival of immunized mice after C. albicans inoculation (Huai et al , ).…”