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.

Citation:
Onkoba N, Mumo RM, Ochanda H, Omwandho C, Ozwara HS, Egwang TG. "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." Journal of biomedical research. 2017.

Abstract:

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
ef cacy of Plasmodium falciparumserine 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. bergheiANKA and P. knowlesiH strain
parasites, respectively. Safety was determined by observing for injection sites reactogenicities, hematology and
clinical chemistry. Parasitaemia and survivorship pro les were used to determine cross-species ef cacy, 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 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.
Keywords: malaria, DNA vaccines, serine repeat antigen, chemokines, cross-species, protection, immunogenicity,
safety

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