CiteULike  View Full Text   View/Add Comment  Download reader    
Nyamongo Onkoba,Ruth M. Mumo,Horace Ochanda,Charles Omwandho,Hastings S. Ozwara,Thomas G. Egwang.Journal of Biomedical Research,2017,31(4):321-332
Safety, immunogenicity, and cross-species protection of aplasmid DNA encoding Plasmodium falciparum SERA5polypeptide, microbial epitopes and chemokine genes in miceand olive baboons
Received:March 16, 2016  Revised:June 14, 2016
DOI10.7555/JBR.31.20160025
Keywordsmalaria, DNA vaccines, serine repeat antigen, chemokines, cross-species, protection, immunogenicity, safety
Grant Program
                 
AuthorInstitution
Nyamongo Onkoba Department of Tropical & Infectious Diseases, Institute of Primate Research, Nairobi P. O. Box 24481-00502, Kenya; 2School of Biological Sciences, University of Nairobi, Nairobi P. O. Box 30197-00100, Kenya
Ruth M. Mumo Department of Tropical & Infectious Diseases, Institute of Primate Research, Nairobi P. O. Box 24481-00502, Kenya;Department of Biochemistry, School of Medicine, University of Nairobi, Nairobi P. O. Box 30197-00100, Kenya
Horace Ochanda School of Biological Sciences, University of Nairobi, Nairobi P. O. Box 30197-00100, Kenya
Charles Omwandho Department of Biochemistry, School of Medicine, University of Nairobi, Nairobi P. O. Box 30197-00100, Kenya;Kirinyaga University College, Kerugoya P. O. Box 143-10300, Kenya;
Hastings S. Ozwara Department of Tropical & Infectious Diseases, Institute of Primate Research, Nairobi P. O. Box 24481-00502, Kenya
Thomas G. Egwang Med-Biotech Laboratories, Kampala P. O. Box 9364, Uganda
Hits: 48
Download times: 58
      
Abstract
      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, 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 Th1-, 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.
Close