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
Nyamongo Onkoba
Ruth M.Mumo
Horace Ochanda
Charles Omwandho
Hastings S.Ozwara
Thomas G.Egwang
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.
机标关键词：Plasmodium falciparumimmune responsesclinical signsDNA vaccinesT cell
论文发表日期：2017-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：12( 321-332 )
英文信息