Elsevier

Ticks and Tick-borne Diseases

Volume 2, Issue 3, September 2011, Pages 151-155
Ticks and Tick-borne Diseases

Original Article
Nest box-deployed bait for delivering oral vaccines to white-footed mice

https://doi.org/10.1016/j.ttbdis.2011.06.001Get rights and content

Abstract

Although a wide range of interventions are available for use in reducing the public health burden of Lyme disease, additional tools are needed. Vaccinating mouse reservoirs may reduce the prevalence of spirochetal infection due to the powerful vector and reservoir competence-modulating effects of anti-outer surface protein A (OspA) antibody. A delivery system for an oral immunogen would be required for field trials of any candidate vaccine. Accordingly, we tested candidate bait preparations that were designed to be environmentally stable, attractive to mice, and non-nutritive. In addition, we determined whether delivery of such baits within nest boxes could effectively target white-footed mice. A peanut butter-scented bait was preferred by mice over a blueberry-scented one. At a deployment rate of 12.5 nest boxes per hectare, more than half of resident mice ingested a rhodamine-containing bait, as demonstrated by fluorescent staining of their vibrissae. We conclude that a peanut butter-scented hardened bait placed within simple wood nest boxes would effectively deliver vaccine to white-footed mice, thereby providing baseline information critical for designing field trials of a candidate oral vaccine.

Introduction

Despite great improvements in public awareness and the availability of acaricidal modes of intervention, the spirochetal agent of Lyme disease now infects more than 20,000 people in the United States every year (Hadler, 2010). The geographical distribution of Lyme disease appears to be increasing as a result of intense development of habitat for housing or recreation and increases in deer density (Brownstein et al., 2005), suggesting that the incidence of this zoonosis may greatly increase over the next decades. Although a variety of interventions at the individual and community level are available, to date risk reduction seems to rarely be undertaken. Deer reduction reduces deer tick (the colloquial name for northern human biting populations of ticks that we refer to as Ixodes dammini, the junior subjective synonym of I. scapularis) densities in discrete sites over the long term (Telford, 2002), but sociopolitical considerations may limit the use of this effective intervention. Habitat modification on a large scale is impractical given constraints on the use of fire to modify the landscape, or the scarcity of funds to maintain brush reduction. Host-targeted acaricides such as Damminix or ‘4 posters’ (Mather et al., 1987, Hoen et al., 2009) based upon coating fur of a host with permethrin or other chemical by means of nesting cotton or an oil wick proximal to bait reduces the density of all host-seeking stages of deer ticks, but their expense and the fact that they must be deployed indefinitely also deters their widespread use. Ground-based spraying of acaricides dramatically reduce tick densities in residential neighborhoods for weeks at a time (Stafford, 1997), but many communities are averse even to the relatively small amounts of low-risk chemicals that may be used in their environment. Public awareness and education remain our most powerful tools, and have undoubtedly reduced risk in many communities where individuals are motivated to use personal protective measures and seek medical attention promptly. At the public health scale, our best hope is to promote the principles of integrated pest management and continue to seek complementary additional strategies.

Additional modes of intervention may help reduce risk. Oral vaccination using a recombinant rabies virus protein in a vaccinia vector has been extensively and safely used to reduce the transmission of rabies within European fox populations and eastern U.S. raccoons. We have previously demonstrated that oral delivery of vaccinia expressing the spirochetal outer surface protein A (OspA) protects mice from Lyme disease spirochetes in the laboratory (Scheckelhoff et al., 2006). Anti-OspA antibody reduces the spirochetal competence of vector ticks (Fikrig et al., 1992) and that of reservoir mice as well (Rosa Brunet et al., 1997). In many northeastern U.S. sites, the white-footed mouse (Peromyscus leucopus) serves as the main reservoir for the agent of Lyme disease (Levine et al., 1985). It may be that oral vaccination of such mice would reduce the force of spirochetal transmission by rendering them non-infectious to ticks (Fikrig et al., 1991, Tsao et al., 2004).

Towards this end, we evaluated a non-nutritive bait formulation designed to effectively deliver candidate vaccines to white-footed mice. In particular, we determined whether a blueberry or peanut butter-scented formulation was more attractive. In addition, we tested the candidate bait formulation using a simple delivery strategy over the course of 2 years at a study site. The proportion of mice that ingested bait was determined by in vivo marking with rhodamine B (Fisher, 1999). The parameters that we developed for bait delivery will greatly facilitate a field trial of an oral transmission-blocking vaccine targeted to white-footed mice.

Section snippets

Bait formulations

Bait blocks (15–25 g, 5 × 5 × 0.75 cm) designated WFM-PB2 (peanut butter scent) and WFM-BB1 (blueberry scent) were developed and produced at FoodSource Lures (Birmingham, Alabama, USA). In addition, 2 textures were evaluated, one with a smooth, hard surface similar to rubber and another with a rough cookie-like surface. Although the exact formulation is proprietary, the bait blocks comprise a hardened alginate and gelatin matrix that is non-nutritive; baits were similar in hardness and flexibility to

Results

To determine which candidate bait formulation would be ingested even in the presence of mouse chow (ad libitum), a choice of 3 bait blocks was presented to each cage. Mice tended to quickly ingest PB2 (Fig. 2) over the 4 days of exposure. We conclude that PB2, even in the presence of rodent chow ad libitum and in either small or large cages, is more attractive than either BB1 or the smooth formulation of PB.

To determine the palatability of our candidate baits comprising either a peanut butter

Discussion

An integrated pest management approach is needed to reduce the risk of acquiring Lyme disease, comprising a spectrum from short (e.g., personal protection) to long-term (deer reduction) approaches (Stafford, 2007). The success of the live recombinant vaccinia virus expressing a rabies virus glycoprotein (Brochier et al., 1991) in reducing the spread of rabies among foxes in Europe and raccoons in the eastern U.S. provides the rationale for a similar approach for other zoonoses. Indeed, attempts

Acknowledgement

We are supported by NIH SBIR/STTR R41AI078631.

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    Current address: Department of Biology, City College of New York, 160 Convent Avenue, New York, NY 10031, USA.

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