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Histidine affinity tags affect MSP1(42) structural stability and immunodominance in mice
Farhat Khan1, Patricia M Legler, Ryan M Mease
1Walter Reed Army Institute of Research, Military Malaria Research Program, Malaria Vaccine Branch, Silver Spring, MD, USA.
Biotechnology Journal
|November 15, 2011
Summary
Adding affinity tags to proteins like malaria vaccine candidate MSP1(42) can alter their structure and immune response. While increasing immunogenicity, His-tags change antibody and T-cell responses, suggesting caution in protein development.
Area of Science:
- Biochemistry
- Immunology
- Protein Engineering
Background:
- Affinity tags aid protein purification but can affect protein properties.
- Merozoite surface protein 1 (MSP1) is a candidate malaria vaccine antigen.
- The impact of affinity tags on protein structure and immunogenicity requires careful evaluation.
Purpose of the Study:
- To investigate the influence of histidine (His) affinity tags on the structure and immunogenicity of Plasmodium falciparum MSP1(42).
- To assess the effects of His-tags on protein expression, solubility, aggregation, and immune responses in mice.
Main Methods:
- Cloning and purification of P. falciparum MSP1(42) (FVO and 3D7 strains) with and without His-tags.
- Analysis of protein structure (secondary structure, thermal denaturation) and aggregation.
- Evaluation of humoral and cellular immune responses in mice.
Main Results:
- His-affinity tags influenced protein expression, solubility, and aggregation.
- His-tagged MSP1(42) proteins induced greater overall immunogenicity.
- The fine specificity of humoral and cellular immune responses was altered by the His-tag.
Conclusions:
- Histidine affinity tags can significantly impact the structural integrity and functional immunogenicity of protein antigens like MSP1(42).
- The benefits of using His-tags in protein development may be offset by unintended alterations in protein structure and immune response profiles.
- Caution is advised when using affinity tags for protein antigen development, particularly for vaccine candidates.

