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Recombinant (F1+V) vaccine protects cynomolgus macaques against pneumonic plague
E D Williamson1, P J Packer, E L Waters
1Dstl PortonDown, Salisbury, Wilts SP4 0JQ, UK. dewilliamson@dstl.gov.uk
Abstract:
Cynomolgus macaques, immunised at the 80 μg dose level with an rF1+rV vaccine (two doses, three weeks apart), were fully protected against pneumonic plague following inhalational exposure to a clinical isolate of Yersinia pestis (strain CO92) at week 8 of the schedule. At this time, all the immunised animals had developed specific IgG titres to rF1 and rV with geometric mean titres of 96.83±20.93 μg/ml and 78.59±12.07 μg/ml, respectively, for the 40 μg dose group; by comparison, the 80 μg dose group had developed titres of 114.4±22.1 and 90.8±15.8 μg/ml to rF1 and rV, respectively, by week 8. For all the immunised animals, sera drawn at week 8 competed with the neutralising and protective Mab7.3 for binding to rV antigen in a competitive ELISA, indicating that a functional antibody response to rV had been induced. All but one of the group immunised at the lower 40 μg dose-level were protected against infection; the single animal which succumbed had significantly reduced antibody responses to both the rF1 and rV antigens. Although a functional titre to rV antigen was detected for this animal, this was insufficient for protection, indicating that there may have been a deficiency in the functional titre to rF1 and underlining the need for immunity to both vaccine antigens to achieve protective efficacy against plague. This candidate vaccine, which has been evaluated as safe and immunogenic in clinical studies, has now been demonstrated to protect cynomolgus macaques, immunised in the clinical regimen, against pneumonic plague.
Insights
A novel plague vaccine demonstrated full protection in cynomolgus macaques against pneumonic plague. This vaccine, targeting Yersinia pestis, induced functional antibody responses, highlighting the importance of dual antigen immunity for effective plague prevention.
Area of Science:
- Infectious Diseases
- Vaccinology
- Microbiology
Background:
- Pneumonic plague remains a significant biothreat.
- Existing plague vaccines have limitations in efficacy and safety.
- Development of effective vaccines against Yersinia pestis is crucial.
Purpose of the Study:
- To evaluate the efficacy of a recombinant F1 and V antigen (rF1+rV) vaccine against pneumonic plague in a non-human primate model.
- To assess the immunogenicity and functional antibody responses induced by the rF1+rV vaccine.
- To determine the protective immunity conferred by different vaccine dosage levels.
Main Methods:
- Cynomolgus macaques were immunized with two doses of the rF1+rV vaccine at 40 μg or 80 μg.
- Animals were challenged via inhalation with Yersinia pestis strain CO92 at week 8 post-vaccination.
- Humoral immune responses, including specific IgG titres and functional antibody assays (competitive ELISA), were measured.
- Protection was assessed based on survival and absence of pneumonic plague.
Main Results:
- The 80 μg dose group showed full protection against pneumonic plague, with high IgG titres to both rF1 and rV antigens.
- The 40 μg dose group demonstrated high protection rates, with one animal succumbing due to insufficient antibody responses.
- Functional antibodies against rV antigen were detected in all vaccinated animals, indicating a functional immune response.
- Antibody titres and functional responses correlated with protection, emphasizing the need for immunity to both vaccine components.
Conclusions:
- The rF1+rV vaccine is safe, immunogenic, and protective against pneumonic plague in cynomolgus macaques at the tested dosage regimen.
- Immunity to both F1 and V antigens is essential for achieving protective efficacy against plague.
- This vaccine candidate represents a promising approach for preventing pneumonic plague.
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