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A Quantum Vaccinomics Approach for the Design and Production of MSP4 Chimeric Antigen for the Control of Anaplasma
José de la Fuente1,2, Alberto Moraga-Fernández1, Pilar Alberdi3
1SaBio, Instituto de Investigación en Recursos Cinegéticos (IREC), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Castilla-La Mancha (UCLM)-Junta de Comunidades de Castilla-La Mancha (JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain.
Abstract:
Anaplasma phagocytophilum Major surface protein 4 (MSP4) plays a role during infection and multiplication in host neutrophils and tick vector cells. Recently, vaccination trials with the A. phagocytophilum antigen MSP4 in sheep showed only partial protection against pathogen infection. However, in rabbits immunized with MSP4, this recombinant antigen was protective. Differences between rabbit and sheep antibody responses are probably associated with the recognition of non-protective epitopes by IgG of immunized lambs. To address this question, we applied quantum vaccinomics to identify and characterize MSP4 protective epitopes by a microarray epitope mapping using sera from vaccinated rabbits and sheep. The identified candidate protective epitopes or immunological quantum were used for the design and production of a chimeric protective antigen. Inhibition assays of A. phagocytophilum infection in human HL60 and Ixodes scapularis tick ISE6 cells evidenced protection by IgG from sheep and rabbits immunized with the chimeric antigen. These results supported that the design of new chimeric candidate protective antigens using quantum vaccinomics to improve the protective capacity of antigens in multiple hosts.
Insights
Quantum vaccinomics identified protective epitopes on Anaplasma phagocytophilum MSP4. A chimeric antigen using these epitopes provided protection in sheep and rabbits, improving vaccine potential.
Area of Science:
- Veterinary immunology
- Molecular vaccinology
- Parasitology
Background:
- Anaplasma phagocytophilum Major Surface Protein 4 (MSP4) is crucial for pathogen infection and multiplication.
- Previous vaccination trials with MSP4 showed variable protection in sheep but efficacy in rabbits.
- Differences in antibody responses, potentially due to non-protective epitopes, may explain the variable protection.
Purpose of the Study:
- To identify and characterize protective epitopes of MSP4 using quantum vaccinomics.
- To design and produce a chimeric protective antigen based on identified epitopes.
- To evaluate the protective efficacy of the chimeric antigen in inhibiting Anaplasma phagocytophilum infection.
Main Methods:
- Applied quantum vaccinomics and microarray epitope mapping using sera from vaccinated rabbits and sheep.
- Designed and produced a chimeric protective antigen incorporating identified candidate protective epitopes.
- Conducted inhibition assays using Anaplasma phagocytophilum in human HL60 and Ixodes scapularis tick ISE6 cells.
Main Results:
- Identified candidate protective epitopes within MSP4.
- Developed a chimeric antigen that elicited protective IgG responses in both sheep and rabbits.
- Demonstrated significant inhibition of Anaplasma phagocytophilum infection in cell cultures using antibodies from chimeric antigen-immunized animals.
Conclusions:
- Quantum vaccinomics is effective for identifying protective epitopes.
- The developed chimeric antigen shows promise for broad-host protection against Anaplasma phagocytophilum.
- This approach can guide the design of improved multi-host protective antigens.
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