Adjuvanticity and protective immunity elicited by Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) microspheres
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1Laboratory of Pertussis, Food and Drug Administration, Bethesda, Maryland 20892-4555.
Abstract:
Purified Bordetella pertussis antigens, encapsulated in biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) microspheres, were evaluated for their immunogenicity and ability to elicit a protective immune response against B. pertussis respiratory infection. Microencapsulated pertussis toxoid, filamentous hemagglutinin, and pertactin all retained their immunogenicity when administered parenterally. Intranasal immunization with a low dose (1 micrograms) of encapsulated filamentous hemagglutinin, pertussis toxoid, or pertactin elicited strong specific immunoglobulin G and immunoglobulin A antibody responses in respiratory secretions that were greater in magnitude than the responses elicited by the same doses of unencapsulated antigen. Intranasal immunization with as little as 1 micrograms of encapsulated pertussis antigen prior to infection reduced the bacterial recovery by 3 log10 CFU. However, intranasal immunization with the same low doses of unencapsulated antigens did not reduce infection. Intranasal administration of a combination of 1 micrograms of each of the microencapsulated pertussis antigens was more effective in reducing bacterial infection than administration of any single microencapsulated antigen. Intranasal administration of microencapsulated B. pertussis antigens elicits high levels of specific antibody coinciding with protection against infection when these microspheres are administered to the respiratory tract. These data provide evidence of the respiratory adjuvanticity of three different DL-PLC microsphere preparations, each of which contains a unique B. pertussis antigen.
Insights
Microencapsulated Bordetella pertussis antigens delivered intranasally provide potent respiratory immunity. This novel approach protects against pertussis infection, unlike unencapsulated antigens.
Area of Science:
- Immunology
- Microbiology
- Biotechnology
Background:
- Pertussis remains a significant respiratory infection concern.
- Traditional vaccines have limitations in eliciting mucosal immunity.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of Bordetella pertussis antigens encapsulated in poly(DL-lactide-co-glycolide) (DL-PLG) microspheres.
- To assess the potential of intranasal immunization with microencapsulated antigens against B. pertussis respiratory infection.
Main Methods:
- Purified B. pertussis antigens (toxoid, filamentous hemagglutinin, pertactin) were encapsulated in DL-PLG microspheres.
- Animals were immunized intranasally with microencapsulated or unencapsulated antigens.
- Humoral immune responses (IgG, IgA) and protection against B. pertussis challenge were assessed.
Main Results:
- Microencapsulated antigens retained immunogenicity and elicited strong specific antibody responses in respiratory secretions.
- Intranasal immunization with low-dose microencapsulated antigens significantly reduced bacterial recovery post-infection.
- Combinations of microencapsulated antigens were more effective than single antigens or unencapsulated forms.
Conclusions:
- DL-PLG microsphere-encapsulated B. pertussis antigens demonstrate respiratory adjuvanticity.
- Intranasal administration of these microencapsulated antigens elicits protective immunity against B. pertussis infection.
- This technology offers a promising strategy for developing effective intranasal pertussis vaccines.