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Published on: July 29, 2022
Immune response variations to Salmonella enterica serovar Typhi recombinant porin proteins in mice
Hoda Toobak1, Iraj Rasooli, Daryush Talei
1Department of Biology, Shahed University, Tehran-Qom Express Way, Opposite Imam Khomeini's Shrine, Tehran 3319118651, Iran.
Objectives:
Typhoid fever is caused by Salmonella enterica serovar Typhi. OmpC, OmpF and OmpA, the three major outer membrane proteins (OMPs), could serve as vaccine candidates.
Methods:
The porins antigenicity was predicted in silico. The OMP genes were amplified, cloned and expressed. Sero-reactivities of the recombinant proteins purified by denaturing method were assayed by ELISA. BALB/c mice were immunized with the recombinant porins followed by bacterial challenge.
Results:
Bacterial challenge of the animal model brought about antibody triggering efficacy of the antigen in OmpF > OmpC > OmpA order. Experimental findings validated the in silico results. None of the antigens had synergic or antagonistic effects on each other from immune system induction points of view. Despite their high immunogenicity, none of the antigens was protective. However, administration of two or three antigens simultaneously resulted in retardation of lethal effect. Porins, in addition to their specific functions, share common functions. Hence, they can compensate for each other's functions.
Conclusions:
The produced antibodies could not eliminate the pathogenicity by blockade of one or some of the antigens. Porin antigens are not suitable vaccine candidates alone or in denatured forms. Native forms of the antigens maybe studied for protective immunogenicity.
Insights
Salmonella Typhi outer membrane proteins (OMPs) showed immunogenicity but not protection against typhoid fever. Denatured OMPs are unsuitable as vaccine candidates alone, but native forms may offer protective immunity.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Typhoid fever is a significant global health concern caused by Salmonella enterica serovar Typhi.
- Major outer membrane proteins (OMPs) like OmpC, OmpF, and OmpA are potential vaccine targets.
Purpose of the Study:
- To evaluate the antigenicity and immunogenicity of Salmonella Typhi OMPs (OmpC, OmpF, OmpA) as potential vaccine candidates.
- To assess the protective efficacy of these OMPs, individually and in combination, in a mouse model.
Main Methods:
- In silico prediction of porin antigenicity.
- Cloning, expression, and purification of recombinant OMPs.
- ELISA to determine sero-reactivity and immunization of BALB/c mice followed by bacterial challenge.
Main Results:
- In silico predictions were validated by experimental results, showing antibody triggering efficacy in the order OmpF > OmpC > OmpA.
- Despite high immunogenicity, none of the individual denatured OMPs provided protection against typhoid challenge.
- Simultaneous administration of multiple OMPs delayed the lethal effect, suggesting functional compensation.
Conclusions:
- Denatured OMPs are not suitable as standalone typhoid vaccine candidates due to insufficient pathogenicity blockade.
- Further investigation into the native forms of these porin antigens is warranted to explore their protective immunogenicity.
