Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection

Abstract

Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

“…It was demonstrated that DNA tattooing induces stronger vaccine-specific immune responses over intramuscular immunization in mice [68,69] and in nonhuman primates [70]. More recently, DNA vaccination by tattoo induced full protection against bacterial challenge in mice in a rapid vaccination protocol [71]. A recent work developed an ex vivo human skin model to determine the factors that control vaccine-induced antigen expression and define the optimal parameters for the evaluation of DNA tattooing in Phase I clinical trials [72].…”

Development of Oral Vaccines Against Lyme Disease

“…Despite these attributes that make OspC a promising vaccine candidate, its function in mammalian infection has remained undefined. Moreover, discrepancies regarding the potential of OspC as a vaccinogen exist in the current literature [69,70,74,[76][77][78][79][80] and should be further elucidated. Aiming to expand our understanding of this antigen, it is pivotal that we revisit important literature findings, reassess their significance and integrate them in future studies of development and testing of OspC-based vaccines.…”

“…Despite this knowledge, the majority of studies that assessed protection conferred by vaccination with OspC used conditions that do not mimic the natural context of spirochete transmission, undervaluing the tick-spirochete interaction. Evaluation of efficacy of OspC-based vaccines by tick challenge is quite scarce [69,70,80], as most authors have been assessing vaccine efficacy using the non-natural route of B. burgdorferi infection [74,76,77,79]. The few who tested their vaccines against tick challenge [69,70,80] used a single strain of B. burgdorferi, neglecting the fact that wild ticks are infected with and transmit multiple heterologous OspC strains to the host [33,55,83,116,117].…”

“…OspC has been intensively investigated as a candidate Lyme Disease vaccinogen as a DNA vaccine [74][75][76] and a recombinant protein-based vaccine [69,[77][78][79][80]. A disadvantage of the OspC vaccine is the heterogeneity of OspC proteins among Borrelia strains.…”

“…A disadvantage of the OspC vaccine is the heterogeneity of OspC proteins among Borrelia strains. Studies have been shown that OspC immunization elicits protective immunity against challenge with homologous B. burgdorferi strains [69,70,74,77,79] but fails to protect from infection with heterologous B. burgdorferi strains [76,78]. Yet, other authors have demonstrated that OspC antibodies fail to confer homologous protection against some B. burgdorferi strains [80].…”