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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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Ixodes scapularis infestations of guinea pigs results in the development of acquired resistance to ticks. Nymphs feeding on: (A) naïve guinea pig shows no redness at the tick bite-sites and (B) repeatedly tick-infested guinea pig shows increased redness around the tick bite-site within 24 h of tick attachment.
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Figure 2: Ixodes scapularis infestations of guinea pigs results in the development of acquired resistance to ticks. Nymphs feeding on: (A) naïve guinea pig shows no redness at the tick bite-sites and (B) repeatedly tick-infested guinea pig shows increased redness around the tick bite-site within 24 h of tick attachment.

Mentions: Several decades ago, William Trager observed that rabbits infested repeatedly with Dermacentor ticks develop a robust immune response against tick components that results in rapid rejection of ticks (Trager, 1939), and since then this phenomenon of acquired tick resistance has been noted in various tick-host models (Wikel and Alarcon-Chaidez, 2001). I scapularis ticks feed successfully on guinea pigs and rabbits, the laboratory models of non-reservoir hosts, at first infestation, but subsequent infestations result in dramatic reduction in feeding and ticks fall off or die within 12–24 h (Allen, 1989). Interestingly, this phenomenon does not occur upon repeated infestations of I. scapularis ticks on the murine host, the chosen reservoir host (Wikel et al., 1997), for reasons that are not well understood. The hallmark of tick resistance is the swelling and redness at the tick bite-site (Figure 2) due to cutaneous basophil hypersensitivity, or the rapid recruitment of basophils to the tick bite-site (Brossard and Fivaz, 1982; Wikel and Alarcon-Chaidez, 2001) and is apparently mediated by the concerted activation of humoral and cellular responses. Recruitment of basophils to the bite site, followed by their degranulation, effectively thwarts tick feeding, and promotes tick mortality by mechanisms that are not fully understood (Brown, 1982; Brown and Askenase, 1983, 1985). It is presumed that salivary proteins secreted into the bite site provoke the immune response in the host that recruits basophils to the site (Brown and Askenase, 1985; Wikel and Alarcon-Chaidez, 2001). Importantly, when B. burgdorferi-infected nymphs were allowed to feed on tick-immune guinea pigs, B. burgdorferi transmission was also dramatically impaired (Nazario et al., 1998; Narasimhan et al., 2007a). Hence, there is an ongoing interest to exploit the phenomenon of acquired tick resistance to identify tick salivary proteins that are natural targets of host immunity (Schuijt et al., 2011b). It is anticipated that this would help define salivary protein candidates that might serve as vaccine targets to block tick feeding and Borrelia transmission.


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

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

Ixodes scapularis infestations of guinea pigs results in the development of acquired resistance to ticks. Nymphs feeding on: (A) naïve guinea pig shows no redness at the tick bite-sites and (B) repeatedly tick-infested guinea pig shows increased redness around the tick bite-site within 24 h of tick attachment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Ixodes scapularis infestations of guinea pigs results in the development of acquired resistance to ticks. Nymphs feeding on: (A) naïve guinea pig shows no redness at the tick bite-sites and (B) repeatedly tick-infested guinea pig shows increased redness around the tick bite-site within 24 h of tick attachment.
Mentions: Several decades ago, William Trager observed that rabbits infested repeatedly with Dermacentor ticks develop a robust immune response against tick components that results in rapid rejection of ticks (Trager, 1939), and since then this phenomenon of acquired tick resistance has been noted in various tick-host models (Wikel and Alarcon-Chaidez, 2001). I scapularis ticks feed successfully on guinea pigs and rabbits, the laboratory models of non-reservoir hosts, at first infestation, but subsequent infestations result in dramatic reduction in feeding and ticks fall off or die within 12–24 h (Allen, 1989). Interestingly, this phenomenon does not occur upon repeated infestations of I. scapularis ticks on the murine host, the chosen reservoir host (Wikel et al., 1997), for reasons that are not well understood. The hallmark of tick resistance is the swelling and redness at the tick bite-site (Figure 2) due to cutaneous basophil hypersensitivity, or the rapid recruitment of basophils to the tick bite-site (Brossard and Fivaz, 1982; Wikel and Alarcon-Chaidez, 2001) and is apparently mediated by the concerted activation of humoral and cellular responses. Recruitment of basophils to the bite site, followed by their degranulation, effectively thwarts tick feeding, and promotes tick mortality by mechanisms that are not fully understood (Brown, 1982; Brown and Askenase, 1983, 1985). It is presumed that salivary proteins secreted into the bite site provoke the immune response in the host that recruits basophils to the site (Brown and Askenase, 1985; Wikel and Alarcon-Chaidez, 2001). Importantly, when B. burgdorferi-infected nymphs were allowed to feed on tick-immune guinea pigs, B. burgdorferi transmission was also dramatically impaired (Nazario et al., 1998; Narasimhan et al., 2007a). Hence, there is an ongoing interest to exploit the phenomenon of acquired tick resistance to identify tick salivary proteins that are natural targets of host immunity (Schuijt et al., 2011b). It is anticipated that this would help define salivary protein candidates that might serve as vaccine targets to block tick feeding and Borrelia transmission.

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