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Short- and long-term efficacy of single-dose subunit vaccines against Yersinia pestis in mice
G W Anderson1, D G Heath, C R Bolt
1Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011, USA.
Abstract:
A single, subcutaneous, 30-microg dose of either a combination of the Yersinia pestis proteins F1+V or a F1-V fusion protein adsorbed to the adjuvant aluminum hydroxide, protected Hsd:ND4 mice for one year against pneumonic plague. The recombinant F1+V vaccine provided significant protection as early as day 14 postimmunization. The current Plague Vaccine USP in a single 0.2-ml dose did not provide significant protection in this mouse model. Antibody titers to F1 and V peaked at approximately 5-12 weeks postimmunization and were still detectable one year later. These F1 and V subunit vaccines may offer effective long-term immunity with a reduced dosage schedule when compared with the presently licensed, formalin-killed, whole-cell vaccine.
Insights
New Yersinia pestis (Y. pestis) subunit vaccines, F1+V and F1-V, protected mice against pneumonic plague for one year. These recombinant vaccines offer potential long-term immunity with reduced dosing compared to current options.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Plague, caused by Yersinia pestis (Y. pestis), remains a significant public health concern.
- Existing plague vaccines have limitations in efficacy or dosage requirements.
- Development of effective and long-lasting plague vaccines is crucial for disease prevention.
Purpose of the Study:
- To evaluate the efficacy of novel Yersinia pestis (Y. pestis) subunit vaccines (F1+V and F1-V) in a mouse model.
- To assess the duration of protection conferred by these recombinant vaccines.
- To compare the protective potential of subunit vaccines against the currently licensed plague vaccine.
Main Methods:
- Subcutaneous administration of a single 30-microg dose of F1+V or F1-V subunit vaccines adsorbed to aluminum hydroxide in Hsd:ND4 mice.
- Challenge with Yersinia pestis to assess protection against pneumonic plague.
- Monitoring of survival and antibody titers (to F1 and V antigens) over a one-year period.
- Comparison with mice receiving the current Plague Vaccine USP.
Main Results:
- A single dose of either F1+V or F1-V subunit vaccine provided significant protection against pneumonic plague for one year.
- Significant protection was observed as early as 14 days post-immunization with the F1+V vaccine.
- Antibody titers to F1 and V peaked at 5-12 weeks and remained detectable after one year.
- The current Plague Vaccine USP did not provide significant protection in this model.
Conclusions:
- Recombinant Yersinia pestis (Y. pestis) F1+V and F1-V subunit vaccines demonstrate potent and long-lasting immunogenicity and protection against plague.
- These subunit vaccines may enable a reduced dosage schedule compared to the licensed formalin-killed, whole-cell vaccine.
- Novel subunit vaccines hold promise for improved plague prevention strategies.