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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
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作者 Nyamongo Onkoba Ruth M.Mumo +3 位作者 Horace Ochanda Charles Omwandho Hastings S.Ozwara Thomas G.Egwang 《The Journal of Biomedical Research》 CAS CSCD 2017年第4期321-332,共12页
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species e... Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending 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 BacilleCalmette 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,Th1-,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 Tregulatory 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. 展开更多
关键词 malaria DNA vaccines serine repeat antigen chemokines cross-species protection immunogenicity safety
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