Immunomodulatory effect of a plasmid expressing CD40 ligand on DNA vaccination against human immunodeficiency virus type-1
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Published on: September 1, 2015
1Department of Bacteriology, Yokohama City University School of Medicine, Japan.
Insights
This study shows that combining a CD40 ligand plasmid with an HIV-1 DNA vaccine boosts immune responses in mice. This combination enhances both cellular and antibody immunity, crucial for developing effective AIDS vaccines.
Area of Science:
- Immunology
- Vaccinology
- Molecular Biology
Background:
- CD40 ligand (CD40L) is a key costimulatory molecule and potent immunomodulator.
- Enhancing immune responses is critical for developing effective vaccines against persistent viral infections like HIV-1.
- Understanding how to modulate both humoral and cellular immunity is essential for vaccine design.
Purpose of the Study:
- To investigate the immunomodulatory effects of co-administering human CD40 ligand expression plasmid (pMEhCD40L) with a human immunodeficiency virus type-1 (HIV-1) DNA vaccine.
- To evaluate the impact of pMEhCD40L on both humoral (antibody) and cellular immune responses in an animal model.
- To determine the potential of this combined approach for enhancing immune responses relevant to Acquired Immune Deficiency Syndrome (AIDS) patients.
Main Methods:
- Mice were inoculated with a combination of pMEhCD40L and an HIV-1 DNA vaccine.
- Humoral immune responses were assessed by measuring antigen-specific immunoglobulin G (IgG) subclasses (IgG1 and IgG2a) and IgA.
- Cellular immune responses were evaluated through delayed-type hypersensitivity (DTH) assays and cytotoxic T lymphocyte (CTL) activity.
- Cytokine production (Th1 and Th2) was analyzed to assess the type of immune response elicited.
Main Results:
- Co-inoculation with pMEhCD40L significantly enhanced antigen-specific IgG antibody responses, particularly IgG2a, without suppressing IgG1.
- The expression of hCD40L failed to induce a mucosal IgA response.
- Both delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) activities were induced in a dose-dependent manner.
- pMEhCD40L enhanced both T helper 1 (Th1) and T helper 2 (Th2) type cytokine production, indicating a balanced immune response.
Conclusions:
- Co-administration of pMEhCD40L with an HIV-1 DNA vaccine effectively enhances antigen-specific humoral and cellular immunity in mice.
- This strategy boosts CTL responses and balanced Th1/Th2 cytokine profiles without compromising humoral immunity.
- The findings suggest that pMEhCD40L is a valuable adjuvant for DNA vaccines, potentially beneficial for enhancing immune responses in Acquired Immune Deficiency Syndrome (AIDS) patients.
Abstract:
CD40 ligand is a costimulatory molecule which acts a potent immunomodulator. We found the mice inoculated with human CD40 ligand expression plasmid (pMEhCD40L) combined with human immunodeficiency virus type-1 (HIV-1) DNA vaccine exhibited both humoral and cellular antigen-specific immunological enhancement. The expression of hCD40L induced predominantly antigen-specific immunoglobulin G (IgG) antibody response while it failed to induce mucosal IgA response. Delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte (CTL) activity were induced in a dose-dependent manner. Examination of the relative levels of the two IgG subclasses showed that co-injection of pMEhCD40L enhanced IgG2a response without suppressing IgG1 response. Similarly, the expression of pMEhCD40L enhanced not only T helper 1 (Th1)- but also Th2-type cytokine production. In conclusion, co-inoculation of pMEhCD40L with DNA vaccine was shown to be a useful way to enhance CTL responses without suppressing the humoral immune response in acquired immune deficiency syndrome (AIDS) patients.
