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Effect of polybasic amines on the immunogenicity of mycobacterial ribonucleic acid
Abstract:
The five polybasic amines, methylated bovine serum albumin (MBSA), protamine sulfate, neomycin sulfate, streptomycin sulfate, and diethylaminoethyl-dextran (DEAE-dextran), were examined to determine their effects on the immunogenic activity of mycobacterial ribonucleic acid (RNA) preparations, and whether they could substitute for Freund incomplete adjuvant (FIA) by protecting the mycobacterial RNA in vivo. These compounds were either emulsified in FIA or not emulsified in FIA. Different results were obtained when these compounds, complexed with mycobacterial RNA, were emulsified in FIA. MBSA, in ratios of mycobacterial RNA-MBSA of 1:0.2 to 1:0.4, had no effect on immunogenic activity. However, when the ratio was increased to 1:1, 1:2, or to 1:4, marked inhibition of the immunogenic activity occurred. Protamine sulfate and neomycin sulfate also inhibited the immunogenic activity of mycobacterial RNA; however, neither streptomycin sulfate nor DEAE-dextran had any effect on immunogenic activity. Without being emulsified in FIA, these five polybasic amines, with the exception of DEAE-dextran, acted only as weak adjuvants for mycobacterial RNA and, therefore, could not be used as substitutes for FIA for the protection of mycobacterial RNA from host nucleases. DEAE-dextran, although not as effective as FIA, afforded some protection for the mycobacterial RNA. DEAE-dextran alone also produced a low degree of nonspecific immunity against tuberculosis. Since MBSA, protamine sulfate, and neomycin sulfate reduce the biological activity of mycobacterial RNA after complexing with it, it is probable that these compounds "mask" the immunogenic sites on the mycobacterial RNA structure.
Insights
Five polybasic amines were tested for their ability to enhance the immunogenicity of mycobacterial RNA. Methylated bovine serum albumin (MBSA), protamine sulfate, and neomycin sulfate inhibited RNA immunogenicity, while streptomycin sulfate and DEAE-dextran did not significantly affect it.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Mycobacterial ribonucleic acid (RNA) possesses immunogenic properties.
- Freund incomplete adjuvant (FIA) is commonly used to enhance immune responses.
- The role of polybasic amines in modulating RNA immunogenicity requires further investigation.
Purpose of the Study:
- To evaluate the effects of five polybasic amines on the immunogenic activity of mycobacterial RNA.
- To determine if these amines could substitute for Freund incomplete adjuvant (FIA) in protecting mycobacterial RNA in vivo.
- To elucidate the mechanism by which these amines interact with mycobacterial RNA.
Main Methods:
- Complexation of mycobacterial RNA with five polybasic amines: methylated bovine serum albumin (MBSA), protamine sulfate, neomycin sulfate, streptomycin sulfate, and diethylaminoethyl-dextran (DEAE-dextran).
- Emulsification of these complexes in FIA or use without emulsification.
- Assessment of the immunogenic activity of the resulting preparations.
- Evaluation of the protective effect of the amines against host nucleases.
Main Results:
- MBSA, protamine sulfate, and neomycin sulfate inhibited mycobacterial RNA immunogenicity in a dose-dependent manner when complexed with RNA.
- Streptomycin sulfate and DEAE-dextran did not significantly affect RNA immunogenicity.
- When not emulsified in FIA, most amines acted as weak adjuvants, with DEAE-dextran providing some protection to RNA and inducing low-level nonspecific immunity against tuberculosis.
Conclusions:
- MBSA, protamine sulfate, and neomycin sulfate likely mask immunogenic sites on mycobacterial RNA, reducing its biological activity.
- These polybasic amines, except for DEAE-dextran, cannot effectively substitute for FIA in protecting mycobacterial RNA.
- DEAE-dextran shows potential as a partial adjuvant and protective agent for mycobacterial RNA, warranting further study.