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Published on: February 29, 2016
Reduced immunogenicity of DNA vaccine plasmids in mixtures
M Sedegah1, Y Charoenvit, L Minh
1Malaria Program, Naval Medical Research Center, Silver Spring, MD, USA.
Abstract:
We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-gamma responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-gamma responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-gamma responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.
Insights
Multiple DNA plasmids for malaria vaccines can suppress immune responses when combined. This study found that using single plasmids induced stronger antibody and interferon-gamma responses than a nine-plasmid mixture, even after poxvirus boosting.
Area of Science:
- Immunology
- Vaccinology
- Molecular Biology
Background:
- DNA vaccines are a promising platform for inducing immune responses against various pathogens.
- Developing multi-target vaccines, such as those for malaria, presents challenges in optimizing immunogenicity.
Purpose of the Study:
- To evaluate the immunogenicity of individual DNA vaccine plasmids encoding malaria antigens.
- To assess the impact of combining multiple plasmids on immune responses (antibody and interferon-gamma).
- To investigate potential immunosuppressive effects within multi-plasmid DNA vaccine formulations.
Main Methods:
- Nine DNA vaccine plasmids encoding candidate malaria antigens were tested individually and as a nine-plasmid mixture.
- Immunosuppressive effects were assessed by replacing individual plasmids with a control plasmid in mixtures.
- Antibody titers and interferon-gamma (IFN-γ) responses were measured.
- Animals were boosted with recombinant poxvirus to assess secondary responses.
Main Results:
- Individual DNA vaccine plasmids induced significant antibody titers and IFN-γ responses.
- Pooling nine plasmids into a single cocktail significantly suppressed immune responses.
- Removing individual genes from the mixture often reduced this suppression.
- Poxvirus boosting enhanced antibody responses but did not overcome the suppressive effects of the mixture.
- Boosting failed to improve IFN-γ responses in animals receiving the plasmid mixture.
Conclusions:
- Interactions between plasmids in a multi-plasmid DNA vaccine can lead to significant suppression of immune responses.
- Using a mixture of DNA plasmids may limit the ability to achieve simultaneous responses against multiple targets.
- Further research is needed to optimize multi-plasmid DNA vaccine design to overcome such suppressive interactions.
