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Protective immunity elicited by rBCG vaccines
C K Stover1, G P Bansal, S Langerman
1PathoGenesis Corp., Seattle, WA.
Developments in Biological Standardization
|January 1, 1994
Summary
Recombinant BCG (rBCG) vaccines show promise for enhancing immune responses. Engineering rBCG to express foreign antigens, particularly as membrane-associated lipoproteins, can improve humoral immunity and mucosal vaccine efficacy.
Area of Science:
- Vaccinology
- Microbial immunology
- Recombinant antigen delivery
Background:
- Bacille Calmette-Guerin (BCG) is a live attenuated vaccine against tuberculosis.
- BCG resides in macrophages, favoring cellular over humoral immune responses.
- Recombinant BCG (rBCG) offers potential as a vaccine vector for delivering foreign antigens.
Purpose of the Study:
- To enhance humoral immune responses elicited by rBCG vaccines.
- To investigate the efficacy of different antigen expression strategies in rBCG.
- To evaluate the potential of rBCG for inducing mucosal immunity.
Main Methods:
- Engineered rBCG to express antigens (OspA, PspA) as cytoplasmic, secreted, or membrane-associated lipoproteins.
- Assessed humoral immune responses (antibody titers and quality) in pre-clinical models.
- Investigated mucosal and systemic immune responses following nasal immunization with rBCG.
Main Results:
- Membrane-associated lipoprotein expression of OspA induced high-titred humoral responses.
- Secreted or membrane-associated PspA improved antibody quality but not titer compared to cytoplasmic expression.
- Nasal immunization with rBCG elicited robust and lasting mucosal immunity at multiple sites.
Conclusions:
- rBCG vaccine strategies can be optimized for improved humoral and mucosal immunity.
- Membrane-associated antigen presentation is a promising approach for enhancing rBCG vaccine efficacy.
- rBCG holds potential for developing vaccines against infectious diseases like Lyme and pneumococcal disease.