Complete Protection Against Yersinia pestis in BALB/c Mouse Model Elicited by Immunization With Inhalable Formulations of rF1-V10 Fusion Protein via Aerosolized Intratracheal Inoculation

Abstract

Pneumonic plague, caused by Yersinia pestis, is an infectious disease with high mortality rates unless treated early with antibiotics. Currently, no FDA-approved vaccine against plague is available for human use. The capsular antigen F1, the low-calcium-response V antigen (LcrV), and the recombinant fusion protein (rF1-LcrV) of Y. pestis are leading subunit vaccine candidates under intense investigation; however, the inability of recombinant antigens to provide complete protection against pneumonic plague in animal models remains a significant concern. In this study, we compared immunoprotection against pneumonic plague provided by rF1, rV10 (a truncation of LcrV), and rF1-V10, and vaccinations delivered via aerosolized intratracheal (i.t.) inoculation or subcutaneous (s.c.) injection. We further considered three vaccine formulations: conventional liquid, dry powder produced by spray freeze drying, or dry powder reconstituted in PBS. The main findings are: (i) rF1-V10 immunization with any formulation via i.t. or s.c. routes conferred 100% protection against Y. pestis i.t. infection; (ii) rF1 or rV10 immunization using i.t. delivery provided significantly stronger protection than rF1 or rV10 immunization via s.c. delivery; and (iii) powder formulations of subunit vaccines induced immune responses and provided protection equivalent to those elicited by unprocessed liquid formulations of vaccines. Our data indicate that immunization with a powder formulation of rF1-V10 vaccines via an i.t. route may be a promising vaccination strategy for providing protective immunity against pneumonic plague.

Manganese‐Based Nanoparticle Vaccine for Combating Fatal Bacterial Pneumonia

“…The LD 50 value was determined to be 20 colony forming units (CFU) per mouse (Figure S15, Supporting Information). [ 19 ] Impressively, all mice in the rF1‐V10@AMMSN group survived and exhibited no noticeable weight loss within 14 days post‐challenge, compared to 30% (3/10) survival in the rF1‐V10 group and 50% (5/10) survival in the rF1‐V10@AMSN group (Figure 3e,f). While the bacterial loads in the spleens and livers of the rF1‐V10, rF1‐V10@AMSN, or rF1‐V10@AMMSN immunized mice were all below the detection limit, the bacterial loads in the lungs of rF1‐V10@AMMSN immunized mice were significantly lower than those of other groups (Figure 3g).…”

“…The LD 50 value was determined to be 20 colony forming units (CFU) per mouse (Figure S15, Supporting Information). [19] Impressively, all mice in the rF1-V10@AMMSN group survived and exhibited no noticeable weight loss within 14 days post-challenge, compared to 30% (3/10) survival in the rF1-V10 group and 50%…”

Inhalable vaccine of bacterial culture supernatant extract mediates protection against fatal pulmonary anthrax

“…Particle morphology was observed in multiple fields under a scanning electron microscope (S-3400N; Hitachi, Tokyo, Japan). The moisture content, volume median diameter (VMD), and mass median aerodynamic diameter (MMAD) of the dry powder vaccines were measured according to previously described methods [ 23 ].…”

“…and s.c., respectively) on days 0, 21, and 42 of the trial. The liquid and dry powder formulations were administered with MicroSprayer Aerosolizer or Dry Powder Insufflator (Huironghe Company, Beijing, China), respectively, following previously described methods [ 23 ].…”

A novel sORF gene mutant strain of Yersinia pestis vaccine EV76 offers enhanced safety and improved protection against plague

“…Those currently under clinical trials are all subunit vaccines based on two antigens: F1 (capsular antigen) and LcrV (low calcium response V antigen, a type 3 secretion system [T3SS] component) [ 13 – 16 ]. Non-encapsulated (F1-negative) Y .…”