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Vaccination against Lyme disease: past, present, and future.

Embers ME, Narasimhan S - Front Cell Infect Microbiol (2013)

Bottom Line: Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an Ixodes spp. tick (deer tick).In this review we discuss the enzootic cycle of B. burgdorferi, and the unique opportunities it poses to block infection or transmission at different levels.We present the correlates of protection for this infectious disease, the pros and cons of past vaccination strategies, and new paradigms for future vaccine design that would include elements of both the vector and the pathogen.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA. members@tulane.edu

ABSTRACT
Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an Ixodes spp. tick (deer tick). Despite improvements in diagnostic tests and public awareness of Lyme disease, the reported cases have increased over the past decade to approximately 30,000 per year. Limitations and failed public acceptance of a human vaccine, comprised of the outer surface A (OspA) lipoprotein of B. burgdorferi, led to its demise, yet current research has opened doors to new strategies for protection against Lyme disease. In this review we discuss the enzootic cycle of B. burgdorferi, and the unique opportunities it poses to block infection or transmission at different levels. We present the correlates of protection for this infectious disease, the pros and cons of past vaccination strategies, and new paradigms for future vaccine design that would include elements of both the vector and the pathogen.

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Temporally changing composition of tick saliva spit into the host skin. Schematic representation of the dynamic tick saliva. Ixodes scapularis engorge on vertebrate host skin for 3–7 days spitting saliva into the host dermis at the bite-site. Salivary composition potentially changes during feeding to confront the different host defense responses.
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Figure 3: Temporally changing composition of tick saliva spit into the host skin. Schematic representation of the dynamic tick saliva. Ixodes scapularis engorge on vertebrate host skin for 3–7 days spitting saliva into the host dermis at the bite-site. Salivary composition potentially changes during feeding to confront the different host defense responses.

Mentions: A careful analysis of the tick salivary transcriptome suggested that the tick salivary proteome might be dynamic, and change during feeding (Narasimhan et al., 2007a). Feeding proceeds not as one “big gulp” nor as a steady “sipping,” but proceeds in phases defined grossly as slow in the first 1–2 days and then rapid in the last 3rd and 4th day (Anderson and Magnarelli, 2008). It is then plausible that the salivary proteome changes to meet feeding phase-specific requirements (Figure 3). Histopathological and molecular examination of the dermis at the tick bite site also showed differences in the composition of the inflammatory milieu that accumulates in the early and late stages of feeding (Krause et al., 2009; Heinze et al., 2012). During the final rapid feeding phase, I. scapularis ticks have been shown to secrete a protein that facilitates release of histamines from neutrophils, mast cells and possibly basophils to increase vasodilation and accelerate the flow of blood to the bite site (Dai et al., 2010). Understanding the dynamics of the tick proteome reveals a possible drawback in the approach to identification of tick salivary proteins targeted by host tick-immunity. Since acquired resistance to tick feeding results in rapid tick rejection within the first 12–24 h of tick attachment, presumably, host immunity is directed against salivary proteins expressed in the early phase and it might be critical to identify this subset of salivary proteins. Perhaps we have to shift the focus away from antigens expressed later in feeding, to antigens expressed early in tick feeding. Targeting salivary proteins expressed early in feeding has the advantage of blocking tick feeding early and blocking the transmission of pathogens such as TBEV, A. phagocytophilum and B. microti that are transmitted earlier in feeding than B. burgdorferi (Goodman et al., 2005). The process to dissect and obtain sufficient amount of proteins or RNA from 12 to 24 h fed salivary glands is tedious. Yet, powerful molecular approaches are now available to circumvent the limitations of this approach and to spur the analysis of the early phase transcriptome and proteome of I. scapularis (Hill and Wikel, 2005).


Vaccination against Lyme disease: past, present, and future.

Embers ME, Narasimhan S - Front Cell Infect Microbiol (2013)

Temporally changing composition of tick saliva spit into the host skin. Schematic representation of the dynamic tick saliva. Ixodes scapularis engorge on vertebrate host skin for 3–7 days spitting saliva into the host dermis at the bite-site. Salivary composition potentially changes during feeding to confront the different host defense responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569838&req=5

Figure 3: Temporally changing composition of tick saliva spit into the host skin. Schematic representation of the dynamic tick saliva. Ixodes scapularis engorge on vertebrate host skin for 3–7 days spitting saliva into the host dermis at the bite-site. Salivary composition potentially changes during feeding to confront the different host defense responses.
Mentions: A careful analysis of the tick salivary transcriptome suggested that the tick salivary proteome might be dynamic, and change during feeding (Narasimhan et al., 2007a). Feeding proceeds not as one “big gulp” nor as a steady “sipping,” but proceeds in phases defined grossly as slow in the first 1–2 days and then rapid in the last 3rd and 4th day (Anderson and Magnarelli, 2008). It is then plausible that the salivary proteome changes to meet feeding phase-specific requirements (Figure 3). Histopathological and molecular examination of the dermis at the tick bite site also showed differences in the composition of the inflammatory milieu that accumulates in the early and late stages of feeding (Krause et al., 2009; Heinze et al., 2012). During the final rapid feeding phase, I. scapularis ticks have been shown to secrete a protein that facilitates release of histamines from neutrophils, mast cells and possibly basophils to increase vasodilation and accelerate the flow of blood to the bite site (Dai et al., 2010). Understanding the dynamics of the tick proteome reveals a possible drawback in the approach to identification of tick salivary proteins targeted by host tick-immunity. Since acquired resistance to tick feeding results in rapid tick rejection within the first 12–24 h of tick attachment, presumably, host immunity is directed against salivary proteins expressed in the early phase and it might be critical to identify this subset of salivary proteins. Perhaps we have to shift the focus away from antigens expressed later in feeding, to antigens expressed early in tick feeding. Targeting salivary proteins expressed early in feeding has the advantage of blocking tick feeding early and blocking the transmission of pathogens such as TBEV, A. phagocytophilum and B. microti that are transmitted earlier in feeding than B. burgdorferi (Goodman et al., 2005). The process to dissect and obtain sufficient amount of proteins or RNA from 12 to 24 h fed salivary glands is tedious. Yet, powerful molecular approaches are now available to circumvent the limitations of this approach and to spur the analysis of the early phase transcriptome and proteome of I. scapularis (Hill and Wikel, 2005).

Bottom Line: Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an Ixodes spp. tick (deer tick).In this review we discuss the enzootic cycle of B. burgdorferi, and the unique opportunities it poses to block infection or transmission at different levels.We present the correlates of protection for this infectious disease, the pros and cons of past vaccination strategies, and new paradigms for future vaccine design that would include elements of both the vector and the pathogen.

View Article: PubMed Central - PubMed

Affiliation: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA. members@tulane.edu

ABSTRACT
Lyme borreliosis is a zoonotic disease caused by Borrelia burgdorferi sensu lato bacteria transmitted to humans and domestic animals by the bite of an Ixodes spp. tick (deer tick). Despite improvements in diagnostic tests and public awareness of Lyme disease, the reported cases have increased over the past decade to approximately 30,000 per year. Limitations and failed public acceptance of a human vaccine, comprised of the outer surface A (OspA) lipoprotein of B. burgdorferi, led to its demise, yet current research has opened doors to new strategies for protection against Lyme disease. In this review we discuss the enzootic cycle of B. burgdorferi, and the unique opportunities it poses to block infection or transmission at different levels. We present the correlates of protection for this infectious disease, the pros and cons of past vaccination strategies, and new paradigms for future vaccine design that would include elements of both the vector and the pathogen.

Show MeSH
Related in: MedlinePlus