Vaccination with chimeric protein induces protection in murine model against ascariasis

• Published in: Vaccine Vol. 39; no. 2; pp. 394 - 401
• Main Authors: de Castro, Joseane C., de Almeida, Laila V., Cardoso, Mariana Santos, Oliveira, Fabricio M. Silva, Nogueira, Denise S., Reis-Cunha, João Luis, Magalhaes, Luisa M.D., Zhan, Bin, Bottazzi, Maria Elena, Hotez, Peter J., Bueno, Lilian L., Bartholomeu, Daniella Castanheira, Fujiwara, Ricardo T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 08-01-2021; Elsevier Limited
• Subjects: Animal models; Animals; Antigens; Antigens, Helminth; Ascariasis - prevention & control; Ascaris; Ascaris sp; B cell epitopes; Chimeric antigens; Deoxyribonucleic acid; Disease Models, Animal; DNA; Epitopes; Female; IgG response; Immunization; Immunoglobulin G; Infections; Inflammation; Lipid A; Lipids; Lungs; Lymphocytes B; Mice; Mice, Inbred BALB C; Monophosphoryl lipid A; Parasites; Peptides; Proteins; Recombinant Fusion Proteins - genetics; Reduction; Vaccination; Vaccine development; Vaccines; Zoonoses; Brazil; United States > US; B cell epitopes; Chimeric antigens; Ascaris sp; Antigens; IgG response
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2020.11.046

•The construction of a chimeric protein leads to enhanced immune protection against Ascaris infection.•Vaccination with chimeric protein induced greater than 70% reduction in larval load after challenge.•Vaccine protection is associated with IgG response and reduced lung inflammation compared to controls.
An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.