Safety, immunogenicity, and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide, microbial epitopes and chemokine genes in mice and olive baboons

摘要

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG),tetanus toxoid (TT) and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 + BCG + TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Thl-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and T-regulatory responses vaccinated animals showed enhanced CD4+ (P ＜ 0.01),CD 8+ T cells (P ＜ 0.001) activation and IgG anti-SE36 antibodies responses (P＜0.001) at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69％ cumulative parasite load reduction and 60％ suppression in baboons (P ＜ 0.05) and enhanced survivorship (P＜ 0.001) with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.