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Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine
Stephen J Elvin1, James E Eyles, Kenneth A Howard
1DSTL, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. SJElvin@dstl.gov.uk
Abstract:
Protection against virulent plague challenge by the parenteral and aerosol routes was afforded by a single administration of microencapsulated Caf1 and LcrV antigens from Yersinia pestis in BALB/c mice. Recombinant Caf1 and LcrV were individually encapsulated in polymeric microspheres, to the surface of which additional antigen was adsorbed. The microspheres containing either Caf1 or LcrV were blended and used to immunise mice on a single occasion, by either the intra-nasal or intra-muscular route. Both routes of immunisation induced systemic and local immune responses, with high levels of serum IgG being developed in response to both vaccine antigens. In Elispot assays, secretion of cytokines by spleen and draining lymph node cells was demonstrated, revealing activation of both Th1 and Th2 associated cytokines; and spleen cells from animals immunised by either route were found to proliferate in vitro in response to both vaccine antigens. Virulent challenge experiments demonstrated that non-invasive immunisation by intra-nasal instillation can provide strong systemic and local immune responses and protect against high level challenge. Microencapsulation of these vaccine antigens has the added advantage that controlled release of the antigens occurs in vivo, so that protective immunity can be induced after only a single immunising dose.
Insights
A single dose of microencapsulated plague antigens (Caf1 and LcrV) from Yersinia pestis protected mice against virulent challenge. This novel vaccine approach offers robust immunity via intranasal or intramuscular routes after just one administration.
Area of Science:
- Bacteriology
- Immunology
- Vaccine Development
Background:
- Yersinia pestis causes plague, a severe infectious disease.
- Effective vaccines are crucial for controlling plague outbreaks.
- Current plague vaccines often require multiple doses.
Purpose of the Study:
- To evaluate the protective efficacy of microencapsulated Yersinia pestis antigens (Caf1 and LcrV).
- To assess immune responses induced by single-dose parenteral and aerosol immunization.
- To determine if intranasal administration can elicit protective immunity.
Main Methods:
- Recombinant Caf1 and LcrV antigens were encapsulated in polymeric microspheres.
- Mice were immunized once via intranasal or intramuscular routes with blended microspheres.
- Immune responses were assessed by serum IgG levels, cytokine secretion (Elispot), and T-cell proliferation.
- Mice were challenged with virulent Yersinia pestis to evaluate protection.
Main Results:
- Single-dose immunization with microencapsulated antigens induced high levels of serum IgG.
- Both Th1 and Th2 cytokines were activated, and spleen cells proliferated in response to antigens.
- Intranasal immunization provided strong systemic and local immune responses.
- Mice immunized via both routes were protected against virulent plague challenge.
Conclusions:
- Single administration of microencapsulated Caf1 and LcrV antigens provides effective protection against plague.
- Intranasal immunization is a viable non-invasive route for inducing protective immunity.
- Controlled antigen release from microspheres enables single-dose vaccination for plague.
Related Concept Videos
Plague
Smallpox
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