Protection against Borreliella burgdorferi infection mediated by a synthetically engineered DNA vaccine

通过合成 DNA 疫苗预防伯氏疏螺旋体感染

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作者:Ghiabe H Guibinga, Bikash Sahay, Heather Brown, Neil Cooch, Jing Chen, Jian Yan, Charles Reed, Meerambika Mishra, Bryan Yung, Holly Pugh, Katherine Schultheis, Rianne N Esquivel, David B Weiner, Laurent H Humeau, Kate E Broderick, Trevor R F Smith

Abstract

Lyme disease is the most common vector-borne disease in North America. The etiological agent is the spirochete Borreliella burgdorferi, transmitted to mammalian hosts by the Ixodes tick. In recent years there has been an increase in the number of cases of Lyme disease. Currently, there is no vaccine on the market for human use. We describe the development of a novel synthetically engineered DNA vaccine, pLD1 targeting the outer-surface protein A (OspA) of Borreliella burgdorferi. Immunization of C3 H/HeN mice with pLD1 elicits robust humoral and cellular immune responses that confer complete protection against a live Borreliella burgdorferi bacterial challenge. We also assessed intradermal (ID) delivery of pLD1 in Hartley guinea pigs, demonstrating the induction of robust and durable humoral immunity that lasts at least 1 year. We provide evidence of the potency of pLD1 by showing that antibodies targeting the OspA epitopes which have been associated with protection are prominently raised in the immunized guinea pigs. The described study provides the basis for the advancement of pDL1 as a potential vaccine for Lyme disease control.

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