Title: 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

 

Authors: Nyamongo Onkoba1,2, Ruth M. Mumo1,3, Horace Ochanda2, Charles Omwandho3,4, Hastings S. Ozwara1, Thomas G. Egwang 5

 

Institutions: 1Department 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; 3Department of Biochemistry, School of Medicine, University of Nairobi, Nairobi P. O. Box 30197-00100, Kenya; 4Kirinyaga University College, Kerugoya P. O. Box 143-10300, Kenya; 5Med-Biotech Laboratories, Kampala P. O. Box 9364, Uganda.

 

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.

 

Keywords: malaria, DNA vaccines, serine repeat antigen, chemokines, cross-species, protection, immunogenicity, safety

 

Full Text: JBR-2016-0025.pdf

 

J Biomed Res published on 25 January, 2017, doi: 10.7555/JBR.31.20160025