Immunogenicity of synthetic peptide constructs based on PvMSP9 E795-A808 , a linear B-cell epitope of the P. vivax Merozoite Surface Protein-9

• Published in: Vaccine Vol. 37; no. 2; p. 306
• Main Authors: Rodrigues-da-Silva, Rodrigo Nunes, Correa-Moreira, Daniely, Soares, Isabela Ferreira, de-Luca, Paula Melo, Totino, Paulo Renato Rivas, Morgado, Fernanda Nazaré, Oliveira Henriques, Maria das Graças de, Peixoto Candea, André Luis, Singh, Balwan, Galinski, Mary R, Moreno, Alberto, Oliveira-Ferreira, Joseli, Lima-Junior, Josué da Costa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Limited 07-01-2019
• Subjects: Animal models; Animals; Antibodies; Antigens; CD4 antigen; Enzyme-linked immunosorbent assay; Epitopes; Immunization; Immunofluorescence; Immunogenicity; Immunoglobulin G; Lymphocytes; Lymphocytes B; Lymphocytes T; Malaria; Mice; Parasites; Peptides; Polymerization; Proteins; R&D; Research & development; Synthetic peptides; Tetanus; Tetanus toxin; Toxins; Vaccines; Vector-borne diseases; γ-Interferon; Antigenicity; Immunogenicity; Malaria; Linear B-cell epitope; Peptide-based immunogens; T-cell epitope
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2018.10.016

Plasmodium vivax Merozoite Surface Protein-9 (PvMSP-9) is a malaria vaccine candidate naturally immunogenic in humans and able to induce high antibody titers in animals when delivered as a recombinant protein. Recently, we identified the sequence EAAPENAEPVHENA (PvMSP9
) as the main linear B-cell epitope in naturally exposed individuals. However, the potential of PvMSP9
as an immunogen in experimental animal models remained unexplored. Here we assess the immunogenicity of PvMSP9
using synthetic peptides. The peptides tested in BALB/c mice include two repeats of the sequence EAAPENAEPVHENA tested alone (peptide RII), or linked to an autologous (PvMSP9 peptide pL; pLRII) or heterologous (p2 tetanus toxin universal T cell epitope; TTRII) T cell epitope. Immune responses were evaluated by ELISA, FLUOROSPOT, and indirect immunofluorescence. We show that all of the peptide constructs tested were immunogenic eliciting specific IgG antibodies at different levels, with a prevalence of IgG1 and IgG2. Animals immunized with synthetic peptides containing T cell epitopes (pLRII or TTRII) had more efficient antibody responses that resulted in higher antibody titers able to recognize the native protein by immunofluorescence. Relevantly, the frequency of IFN-γ secreting SFC elicited by immunization with TTRII synthetic peptide was comparable to that reported to the PvMSP9-Nt recombinant protein. Taken together, our study indicates that PvMSP9
is highly immunogenic in mice and further studies to evaluate its value as promising vaccine target are warranted. Moreover, our study supports the critical role of CD4 T cell epitopes to enhance humoral responses induced by subunit based vaccines.