The Lyme Disease Vaccine: Conception, Development, and Implementation

Thanassi, Wendy; Schoen, Robert T.

doi:10.7326/0003-4819-132-8-200004180-00009

Cited by 55 publications

(22 citation statements)

References 60 publications

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“…OspA is mainly expressed while the spirochetes persist in the tick and the expression of OspA is already down-regulated when the pathogen is transmitted to the human host. The OspA vaccine leads to a 70 -90% protection (10,11,13). On the other hand, OspC is preferentially expressed in the mammalian host.…”

mentioning

confidence: 99%

The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi

Hellwage

Meri

Heikkilä

et al. 2001

Journal of Biological Chemistry

327

309

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Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.

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confidence: 99%

The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi

Hellwage

Meri

Heikkilä

et al. 2001

Journal of Biological Chemistry

327

309

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“…Effective vaccines containing OMPs have been developed for Lyme disease and pertussis (7,17,23,47,49). Several characteristics should be considered when evaluating an OMP as a vaccine candidate, including expression of the protein on the bacterial surface during human infection, conservation of the protein among strains, and the ability to induce a protective immune response (9, 18).…”

mentioning

confidence: 99%

Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

et al. 2005

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Moraxella catarrhalis is an important cause of respiratory infections in adults with chronic obstructive pulmonary disease (COPD) and of otitis media in children. Outer membrane protein (OMP) G1a is an ϳ29-kDa surface lipoprotein and is a potential vaccine candidate. The gene that encodes OMP G1a was expressed and purified using a novel plasmid vector. [ 3 H]palmitic acid labeling demonstrated that both native and recombinant OMP G1a contain covalently bound palmitic acid. To assess the expression of OMP G1a during human infection, paired sera and sputum supernatants from adults with COPD followed prospectively were studied by enzyme-linked immunosorbent assays with recombinant lipidated OMP G1a to detect antibodies made specifically during carriage of M. catarrhalis. Overall, 23% of patients developed either a serum immunoglobulin G (IgG) response (9%) or sputum IgA response (21%) to OMP G1a, following 100 episodes of acquisition and clearance of M. catarrhalis. Patients developed antibody responses at similar rates following episodes of clinical exacerbation compared to asymptomatic colonization. Serum IgG antibodies following natural infection were directed predominantly at OMP G1a epitopes that are not exposed on the bacterial surface. These data show that OMP G1a is expressed during infection of the human respiratory tract and is a target of systemic and mucosal antibodies. These observations indicate that OMP G1a, a highly conserved surface protein, should be evaluated further as a vaccine candidate.Over the past 2 decades, Moraxella catarrhalis has emerged as an important human respiratory pathogen. Acquisition of a new strain of M. catarrhalis is associated with the development of an exacerbation in patients with chronic obstructive pulmonary disease (COPD) (43). Indeed, M. catarrhalis is the second most common bacterial cause of exacerbations in adults with COPD after nontypeable Haemophilus influenzae (32,38,44). COPD is the fourth-leading cause of death in the United States and is projected to rank fifth in the world by 2020 (2,26,28,39). M. catarrhalis is also the third-most-common bacterial cause of otitis media in children after Streptococcus pneumoniae and nontypeable H. influenzae (25). Approximately 25 million episodes of otitis media occur annually in the United States, and $2 billion is spent annually on treatment (25). It is estimated that M. catarrhalis causes 10% to 20% of cases of acute otitis media. Recurrent otitis media in infants and young children affects speech development and cognitive abilities (25, 42). Finally, M. catarrhalis is also a common cause of sinusitis in children and adults (32). Since M. catarrhalis is an important human pathogen for infants and adults with COPD, there is a need for a vaccine. Infants could be immunized to prevent otitis media and adults with COPD could be immunized to prevent exacerbations caused by M. catarrhalis.One approach to vaccine development for gram-negative bacteria has been to use outer membrane proteins (OMPs) as vaccine antigens. Effectiv...

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“…On few occasions, inoculation may occur earlier if spirochetes are already present in the salivary glands of the infected tick (Alekseev et al, 1995). Though, for proper B. burgdorferi transmission to occur an infected tick must attach for at least 24 hours on the animal (Thanassi & Schoen 2000), its transmission to the host has been seen to occur as early as 18 hours after attachment (Alekseev et al, 1995). Concurrent infection with other tick-borne pathogens like Anaplasma phagocytophilum (Persing 1997) and Theileria equi (Basile et al, 2015) can occur.…”

Section: Pathophysiologymentioning

confidence: 99%

Lyme borreliosis in the horse: A mini-review

Kolk¹

2016

JEBAS

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Lyme borreliosis is a multisystemic tick borne disease (also called Lyme disease in humans) which is caused by the Borrelia burgdorferi sensu lato species complex. It is a thin, elongated Gram-negative bacterium and exhibiting motility with flagellar projections. Affected animals mainly show cranial or peripheral neuropathies and uveitis as the more commonly seen extraneural manifestation. Serological evidences confirm its higher occurrence in elderly horses than young ones. Although, incidence of equine Lyme borreliosis is low, its diagnosis is a real challenge. As no indisputable test exists for detecting antibodies to B. burgdorferi, histopathology remains the gold standard and might reveal vascular sclerosis and pleocellular inflammatory infiltrates in neural tissue. Despite antibiotic treatment clinical signs might progress or recur. This review converses with the disease etiology, pathobiology in brief and its mangment from publich health point of view.

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The Lyme Disease Vaccine: Conception, Development, and Implementation

Cited by 55 publications

References 60 publications

The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi

The Complement Regulator Factor H Binds to the Surface Protein OspE of Borrelia burgdorferi

Human Antibody Response to Outer Membrane Protein G1a, a Lipoprotein of Moraxella catarrhalis

Lyme borreliosis in the horse: A mini-review

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