|Author:||Lam, Ka Wai|
|Title:||Damage-associated molecular pattern S100A4 : a potential adjuvant for mucosal immunization|
|Advisors:||Zou, Xiang (HTI)|
|Subject:||Mucous membrane -- Immunology|
Hong Kong Polytechnic University -- Dissertations
|Department:||Department of Health Technology and Informatics|
|Pages:||ix, 64 pages : color illustrations|
Pathogenic microorganisms, including bacteria, viruses, fungi and parasites, can enter the human body through different routes. Mucosal membrane is often the first site of entry although different types of mucosa-associated lymphoid tissue (MALT) responsible for providing physical, chemical and immunological protection against foreign pathogens are present in the human body. Mucosal infections, such as influenza and COVID-19 pandemic, have been causing high morbidity and mortality in humans. Mucosal immunization is an effective strategy for prevention of mucosal infections. However, due to the immunotolerance effect produced by mucosal membranes, the immunogenicity of mucosal vaccine is unacceptably low. The use of adjuvant may be a possible solution to this inherent problem. Among different adjuvants, the damage-associated molecular pattern (DAMP) molecule S100A4 may be a potential candidate for eliciting a strong mucosal immune response.
This study aims at investigating the effects of DAMP molecule S100A4 as an mucosal adjuvant for intranasal immunization.
Mice were intranasally immunized three times with model antigen ovalbumin (OVA; 10 μg) alone, or admixed to S100A4 (10 μg) or cholera toxin (CT; 1 μg) at a 10-day interval and blood and lung samples were collected 10 days after the last immunization for investigation. Two experiments were performed on the serum and lung samples. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum OVA-specific total IgG and IgG subclass (IgG1 and IgG2c) antibody titers. Flow cytometry analysis was performed to measure the activation of OVA-specific cytotoxic T lymphocytes.
Anti-OVA total IgG, IgG1 and IgG2c levels in mice serum were significantly enhanced after immunization adjuvanted with the DAMP molecule S100A4. S100A4 as an adjuvant after intranasal immunization also augmented the antigen specific cytotoxic T lymphocytes activation in the lungs.
The results suggested that intranasal immunization adjuvanted with S100A4 can trigger greater humoral and cellular immune response. However, further studies are needed more convincing conclusion.
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