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 ofPlasmodium 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 withP. 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.
Highlights
The rapid emergence of malaria parasite drug resistance to drugs of choice and anopheline mosquito vector insecticide resistance threatens current gains made in rolling back malaria[1]
Our findings showed that pSeBCGTT/chemokines plasmid DNA vaccine candidate were safe, immunogenic and conferred partial cross-species protection against P. knowlesi and P. berghei ANKA parasites in olive baboons and mice respectively
Our study has shown for the first time that the pSeBCGTT DNA vaccine candidate incorporating C-C chemokines is immunogenic in animal models and induces partial cross-species protection in mice against heterologous blood-stage P. berghei ANKA challenge and baboons against P. knowlesi H strain
Summary
The rapid emergence of malaria parasite drug resistance to drugs of choice and anopheline mosquito vector insecticide resistance threatens current gains made in rolling back malaria[1] This has reinvigorated the search for effective human malaria vaccines[2]. The prevalence of infections with the less prevalent P. ovale and P. malariae species seem to be increasing despite reported decreasing morbidity and mortality rates caused by P. falciparum worldwide[1,8]. This alarming trend suggests that future malaria vaccine development efforts should include the development of DNA based vaccines that are safe, immunogenic, and can confer cross-species protection. The current progress toward malaria vaccines development has been slow largely due to malaria parasite antigenic diversity and allelic heterogeneity, gaps in our knowledge about protective antigens, appropriate adjuvants for human use, and lack of suitable animal models for pre-clinical vaccine evaluation[9,10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
