Inclusion of the murine IgGκ signal peptide increases the cellular immunogenicity of a simian adenoviral vectored Plasmodium vivax multistage vaccine. Issue 20 (11th May 2018)

• Record Type: Journal Article
• Authors: Fonseca, Jairo A.; McCaffery, Jessica N.; Caceres, Juan; Kashentseva, Elena; Singh, Balwan; Dmitriev, Igor P.; Curiel, David T.; Moreno, Alberto
• Is Part Of: Vaccine. Volume 36:Issue 20(2018)
• Page Start: 2799
• Page End: 2808
• Publication Date: 2018-05-11
• Subjects: Malaria -- Plasmodium vivax -- Simian adenovirus vector -- Adenoviral vector -- Signal peptide -- Signal sequence -- Heterologous prime-boost immunization -- Immunogenicity; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.03.091
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: The murine IgGκ signal peptide was included in the Simian Adenovirus 36 vector. A P. vivax multi-stage vaccine candidate was encoded downstream of the SP. Mice were immunized with the unmodified or SP-SAd36 vector, and two protein boosts. SP-SAd36 immunization induced higher antibody avidity. SP-SAd36 immunization induced more IFN-γ and IL-2-secreting CD4 T cells. Abstract: Introduction: Cellular and humoral immune responses are both involved in protection against Plasmodium infections. The only malaria vaccine available, RTS, S, primarily induces short-lived antibodies and targets only a pre-erythrocytic stage antigen. Inclusion of erythrocytic stage targets and enhancing cellular immunogenicity are likely necessary for developing an effective second-generation malaria vaccine. Adenovirus vectors have been used to improve the immunogenicity of protein-based vaccines. However, the clinical assessment of adenoviral-vectored malaria vaccines candidates has shown the induction of robust Plasmodium -specific CD8+ but not CD4+ T cells. Signal peptides (SP) have been used to enhance the immunogenicity of DNA vaccines, but have not been tested in viral vector vaccine platforms. Objectives: The objective of this study was to determine if the addition of the SP derived from the murine IgGκ light chain within a recombinant adenovirus vector encoding a multistage P. vivax vaccine candidate could improve the CD4+ T cell response. Methods: In this proof-of-concept study, we immunized CB6F1/J mice with either the recombinant simian adenovirus 36 vector containing the SP (SP-SAd36) upstream from a transgene encoding a chimeric P. vivax multistage protein or the same SAd36 vector without the SP. Mice were subsequently boosted twice with the corresponding recombinant proteins emulsified in Montanide ISA 51 VG. Immunogenicity was assessed by measurement of antibody quantity and quality, and cytokine production by T cells after the final immunization. Results: The SP-SAd36 immunization regimen induced significantly higher antibody avidity against the chimeric P. vivax proteins tested and higher frequencies of IFN-γ and IL-2 CD4+ and CD8+ secreting T cells, when compared to the unmodified SAd36 vector. Conclusions: The addition of the murine IgGκ signal peptide significantly enhances the immunogenicity of a SAd36 vectored P. vivax multi-stage vaccine candidate in mice. The potential of this approach to improve upon existing viral vector vaccine platforms warrants further investigation.