A multi-epitope DNA vaccine co-administered with monophosphoryl lipid A adjuvant provides protection against tick transmitted Ehrlichia ruminantium in sheep

• Published in: Vaccine Vol. 37; no. 31; pp. 4354 - 4363
• Main Authors: Tshilwane, S.I., Thema, N., Steyn, H.C., van Kleef, M., Pretorius, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 18.07.2019; Elsevier Limited
• Subjects: Adjuvants; Antigens; CD4 antigen; CD8 antigen; Cell activation; Cytokines; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA vaccines; Drug delivery systems; E. ruminantium; Ehrlichia ruminantium; Epitopes; Gene guns; Heartwater fever; Immunological memory; Inoculation; Lipid A; Lipids; Lymphocytes; Lymphocytes T; Memory cells; Monophosphoryl lipid A; Multi-epitope DNA vaccine; Ovis aries; Peptides; Sheep; Tick challenge; Topical application; Vaccines; E. ruminantium; Monophosphoryl lipid A; Multi-epitope DNA vaccine; Tick challenge
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.06.027

•E. ruminantium peptides formulated in multi-epitope DNA vaccine constructs induced Th1 immunity in vitro.•pLamp multi-epitope DNA vaccine construct induced improved Th1 immune responses.•Co-administration of pLamp with MPL adjuvant protected 60% of sheep against E. ruminantium tick challenge. Previously, a heartwater experimental DNA vaccine provided 100% protection following laboratory challenge with Ehrlichia ruminantium administered by needle but not against an E. ruminantium tick challenge in the field. A multi-epitope DNA vaccine incorporating both CD4+ and CD8+ cytotoxic T lymphocytes epitopes could provide a better alternative. In this study, we investigated the use of multi-epitope DNA vaccines against an E. ruminantium experimental tick challenge in sheep. The multi-epitope DNA vaccines were delivered via the intramuscular route and intradermal route using the gene gun in the presence of monophosphoryl lipid A (MPL) adjuvant, which was either applied topically to the gene gun inoculation site or co-administered with the vaccine via the intramuscular route. Initially two constructs namely, pSignal plus and pLamp were tested with MPL applied topically only and no protection was obtained in this formulation. However, when pLamp was co-administered with MPL via the intramuscular route in addition to topical application, its protective efficiency improved to protect 60% of the sheep against tick challenge. In this formulation, the vaccine induced enhanced activation of memory T cell responses both before and after challenge with variations amongst the different sheep possibly due to their different genetic backgrounds. In conclusion, this study showed that a heartwater multi-epitope DNA vaccine, co-administered with MPL adjuvant can protect sheep following a laboratory E. ruminantium tick challenge.