Microencapsulation of viral or bacterial antigens has been found to enhance antigen-specific immune responses in experimental animals. The promise of these findings has encouraged studies of microencapsulated antigens in adult volunteers. However, little is known about the mechanisms by which microencapsulation enhances the immune response, the capacity of microencapsulation to induce an immune response which protects against challenge, or the potential for microencapsulation to perturb antigen-specific immune responses. For example, micro- encapsulated viruses inoculated orally may bypass antigen presentation by mucosal epithelial cells, select for antigen uptake by macrophages, and protect virus from exposure to mucosal proteases. These changes may perturb the balance between virus-specific humoral and cellular immune responseS or alter the proteins recognized by virus-specific antibodies or cytotoxic T lymphocytes (CTLs). We recently developed a system of microencapsulation using aqueous anionic polymers and aqueous amines (charged-film microcapsules). The capacity of water-soluble reagents to encapsulate infectious virus obviates concerns about loss of antigenicity associated with organic solvent-based systems of microencapsulation. Using the intestinal pathogen, rotavirus, we found that charged-film microcapsules have the capacity to enhance rotavirus immunogenicity after oral inoculation of mice. We will extend these observations by addressing the following questions: 1) What are the mechanisms by which microencapsulation of virus enhances virus-specific immunity? 2) Does oral inoculation of mice with microencapsulated preparations of rotavirus or rotavirus proteins alter the magnitude of or balance between virus-specific humoral and cellular responses? 3) Does microencapsulation of rotavirus alter the fine antigenic specificities of virus-specific neutralizing antibodies or CTLs? 4) Does oral inoculation of mice with microencapsulated virus or viral proteins enhance the capacity of immunization to protect against challenge?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026251-08
Application #
2429379
Study Section
Experimental Virology Study Section (EVR)
Project Start
1990-01-01
Project End
2000-05-31
Budget Start
1997-06-01
Budget End
1998-05-31
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Moser, C A; Offit, P A (2001) Distribution of rotavirus-specific memory B cells in gut-associated lymphoid tissue after primary immunization. J Gen Virol 82:2271-4
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Coffin, S E; Clark, S L; Bos, N A et al. (1999) Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization. J Immunol 163:3064-70
Moser, C A; Speaker, T J; Offit, P A (1998) Effect of water-based microencapsulation on protection against EDIM rotavirus challenge in mice. J Virol 72:3859-62
Brown, K A; Offit, P A (1998) Rotavirus-specific proteins are detected in murine macrophages in both intestinal and extraintestinal lymphoid tissues. Microb Pathog 24:327-31
Moser, C A; Cookinham, S; Coffin, S E et al. (1998) Relative importance of rotavirus-specific effector and memory B cells in protection against challenge. J Virol 72:1108-14
Coffin, S E; Offit, P A (1998) Induction of mucosal B-cell memory by intramuscular inoculation of mice with rotavirus. J Virol 72:3479-83
Coffin, S E; Moser, C A; Cohen, S et al. (1997) Immunologic correlates of protection against rotavirus challenge after intramuscular immunization of mice. J Virol 71:7851-6
Moser, C A; Speaker, T J; Offit, P A (1997) Effect of microencapsulation on immunogenicity of a bovine herpes virus glycoprotein and inactivated influenza virus in mice. Vaccine 15:1767-72

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