Reservoir targeted vaccine against Borrelia burgdorferi: a new strategy to prevent Lyme disease transmission

Abstract

A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A-specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease.

Keywords: Borrelia burgdorferi; Lyme disease; Oral vaccine; enzootic cycle; transmission; wildlife reservoir.

Figure 1.

Proposed strategy to break the enzootic cycle of the Lyme disease spirochete. A, The triad which comprises the enzootic cycle: the tick vector (Ixodes scapularis), the major reservoir host (white footed-mouse), and Borrelia burgdorferi. B, Hypothesis: immunizing wild white-footed mice with oral reservoir-targeted vaccine (RTV) breaks the enzootic cycle of B. burgdorferi. C, Field study design and methods. Abbreviations: Ab, antibody; Ctrl, control plot; FlaB, Flagellin B; OspA, outer surface protein A; PCR, polymerase chain reaction.

Figure 2.

Analysis of the antibody response to outer surface protein A (OspA) as a function of the minimum effective dose (ie, 5 reservoir-targeted vaccine [RTV] units) in white-footed mice trapped in 2 distinct plots in suburban New York in 2008 (38 mice in plot NY1 and 30 mice in plot NY2). P values were determined by the Mann–Whitney U test.

Figure 3.

Anti–outer surface protein A (OspA) antibody (Ab) distribution between plots with and plots without deployment of reservoir-targeted vaccine (RTV). Blood specimens from trapped mice were tested for the presence of OspA-specific Ab by enzyme-linked immunosorbent assay. A, Mice were trapped in RTV-deployed plots NY1 and NY2 and untreated control plots during 2008–2011. B, Mice were trapped in RTV-deployed plots NY3 and NY4 and untreated control plots during 2009–2011. Vaccination resulted in a statistically significant increase in the anti-OspA Ab response after control for natural variation among plots and years, using a generalized linear mixed model (P = .002). Multiple pairwise comparisons of means by use of the Tukey honest significant difference post-hoc test revealed that differences in anti-OspA–specific Ab levels between mice captured in the vaccine plots and those captured in the control plots were statistically significant for all plots except NY3. Statistical analysis of the protective seroprevalence data was done using the χ² test. 2010 data were not included for NY3 because both values were 0.

Figure 4.

Borrelia burgdorferi infection in nymphal Ixodes scapularis ticks in plots where an oral reservoir-targeted vaccine (RTV) for wild white-footed mice were deployed. A, C, E, G, and I, Proportion of ticks infected with B. burgdorferi from control plots (A); from the NY1 plot, in which RTV was deployed for 5 consecutive years (C); from the NY2 plot, in which RTV was deployed for 4 years (E); and from the NY3 plot (G) and the NY4 plot (I), in which RTV was deployed for 3 years. B, D, F, and H, Nymphal infection prevalence (NIP) normalized against the baseline vs the control for the same years of treatment. Given that RTV is expected to exert an effect 1 year after deployment, the baseline NIP is the NIP recorded in the first year of the study. P values were determined by the χ² test.

Figure 5.

Percentage difference from baseline in the nymphal infection prevalence (NIP) after long-term deployment of reservoir-targeted vaccine (RTV), by duration of deployment. For 2-year deployment, NIP was calculated as the difference between the average proportions for years 1 and 2 (for plot NY1, 2008 and 2007; for plot NY2, 2009 and 2008; for plot NY3, 2010 and 2009; and for plot NY4, 2010 and 2009); for 3-year deployment, the difference between the average proportions for years 1 and 3 was used (for plot NY1, 2009 and 2007; for plot NY2, 2010 and 2008; for plot NY3, 2011 and 2009; and for plot NY4, 2011 and 2009); for 4-year deployment, the difference between the average proportions for years 1 and 4 was used (for plot NY1, 2010 and 2007; and for plot NY2, 2011 and 2008); and for 5-year deployment, the difference between the average proportions for years 1 and 5 was used (for plot NY1, 2011 and 2007). P = 4.7×10⁻⁵, by generalized linear mixed modeling. Abbreviation: EC, enzootic cycle.