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Ticks and tick-borne diseases are on the rise due to socioecosystemic changes and climate modification and are affecting human and animal health. Few vaccines are available. Two recent articles from Matias et al. and Pine et al. used mRNA technology to explore tick and pathogen proteins as vaccine candidates.
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Enfermedades por Picaduras de Garrapatas , Garrapatas , Vacunas , Animales , Humanos , Enfermedades por Picaduras de Garrapatas/prevención & controlRESUMEN
(1) Background: The incidence of Lyme borreliosis (LB) is increasing in Europe. The new LB vaccine is still in clinical development, thus the dissemination of knowledge about the disease is essential. We assessed the knowledge, attitudes and preventive practices (KAP) against tick-borne diseases (TBDs) of people living in the endemic area in northeastern Poland. (2) Methods: We surveyed 406 adults using a 37-item anonymous paper survey. The data were analyzed with regression models. (3) Results: The two most popular knowledge sources were the Internet and doctors, selected by 77.8% and 53.4%, respectively. Respondents felt moderately knowledgeable about TBDs and tick bite prophylaxis (median scores 5/10, and 6/10, respectively), considered TBDs to be a significant health threat (median 8/10), attributed high risk to tick mouthparts remaining in the skin after tick removal (median 10/10), and shared multiple misconceptions regarding LB transmission, symptoms, and management. General knowledge scores (GKS) about TBDs and tick protection practices scores (TPS) were moderate (65.0%; IQR, 55.8−71.7%, 63.6%; 54.5−72.7%, respectively). Only 48.0% had a positive attitude towards TBE vaccination. A recent tick-bite was associated with higher GKS (OR, 2.55; 95% CI, 1.27−5.10; p = 0.008), higher TPS (OR 4.76, 95% CI, 2.0−11.1; p < 0.001), and a positive attitude towards TBE vaccine (OR 2.10, 1.07−4.10, p = 0.030). A positive vaccine attitude was also associated with obtaining TBD knowledge from doctors and other verified sources (OR, 2.654, 1.66−4.23; p < 0.001). Age, place of residence, and frequent exposure to ticks in green areas were not associated with GKS, TPS, nor vaccine attitude. (4) Conclusions: Increased risk perceptions are associated with adoption of behaviors preventing TBDs. Medical professionals play an important role in communicating knowledge about TBDs. There is a need to revise current communication strategies with respect to tick bites and prevention of LB and other TBDs.
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Purpose: Vaccine effectiveness (VE) studies are often conducted after the introduction of new vaccines to ensure they provide protection in real-world settings. Control of confounding is often needed during the analyses, which is most efficiently done through multivariable modeling. When many confounders are being considered, it can be challenging to know which variables need to be included in the final model. We propose an intuitive Bayesian model averaging (BMA) framework for this task. Patients and Methods: Data were used from a matched case-control study that aimed to assess the effectiveness of the Lyme vaccine post-licensure. Cases were residents of Connecticut, 15-70 years of age with confirmed Lyme disease. Up to 2 healthy controls were matched to each case subject by age. All participants were interviewed, and medical records were reviewed to ascertain immunization history and evaluate potential confounders. BMA was used to systematically search for potential models and calculate the weighted average VE estimate from the top subset of models. The performance of BMA was compared to three traditional single-best-model-selection methods: two-stage selection, stepwise elimination, and the leaps and bounds algorithm. Results: The analysis included 358 cases and 554 matched controls. VE ranged between 56% and 73% and 95% confidence intervals crossed zero in <5% of all candidate models. Averaging across the top 15 models, the BMA VE was 69% (95% CI: 18-88%). The two-stage, stepwise, and leaps and bounds algorithm yielded VE of 71% (95% CI: 21-90%), 73% (95% CI: 26-90%), and 74% (95% CI: 27-91%), respectively. Conclusion: This paper highlights how the BMA framework can be used to generate transparent and robust estimates of VE. The BMA-derived VE and confidence intervals were similar to those estimated using traditional methods. However, by incorporating model uncertainty into the parameter estimation, BMA can lend additional rigor and credibility to a well-designed study.
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Lyme disease (LD) is a tick-transmitted bacterial infection caused by Borreliella burgdorferi and other closely related species collectively referred to as the LD spirochetes. The LD spirochetes encode an uncharacterized family of proteins originally designated protein family twelve (PF12). In B. burgdorferi strain B31, PF12 consists of four plasmid-carried genes, encoding BBK01, BBG01, BBH37, and BBJ08. Henceforth, we designate the PF12 proteins family twelve lipoprotein (Ftl) A (FtlA) (BBK01), FtlB (BBG01), FtlC (BBH37), and FtlD (BBJ08). The goal of this study was to assess the potential utility of the Ftl proteins in subunit vaccine development. Immunoblot analyses of LD spirochete cell lysates demonstrated that one or more of the Ftl proteins are produced by most LD isolates during cultivation. The Ftl proteins were verified to be membrane associated, and nondenaturing PAGE revealed that FtlA, FtlB, and FtlD formed dimers, while FtlC formed hexamers. Analysis of serum samples from B. burgdorferi antibody (Ab)-positive client-owned dogs (n = 50) and horses (n = 90) revealed that a majority were anti-Ftl Ab positive. Abs to the Ftl proteins were detected in serum samples from laboratory-infected dogs out to 497 days postinfection. Anti-FtlA and FtlB antisera displayed potent complement-dependent Ab-mediated killing activity, and epitope localization revealed that the bactericidal epitopes reside within the N-terminal domain of the Ftl proteins. This study suggests that FtlA and FtlB are potential candidates for inclusion in a multivalent vaccine for LD.
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Borrelia burgdorferi , Ixodes , Enfermedad de Lyme , Animales , Perros , Anticuerpos Antibacterianos , Antígenos Bacterianos , Proteínas de la Membrana Bacteriana Externa/genética , Epítopos , Caballos , Sueros Inmunes , Ixodes/microbiología , Lipoproteínas/genética , Enfermedad de Lyme/microbiología , Vacunas Combinadas , Vacunas de Subunidad/genéticaRESUMEN
We conducted a matched case-control study to assess the effectiveness of Lyme vaccine (LYMErix) as it was used in clinical practice. We found ≥3 doses to be 71% effective against Lyme disease. This is the first study to show that the Lyme vaccine is effective in a real-world setting.
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Experimental Outer surface protein (Osp) C based subunit chimeritope vaccinogens for Lyme disease (LD) were assessed for immunogenicity, structure, ability to elicit antibody (Ab) responses to divergent OspC proteins, and bactericidal activity. Chimeritopes are chimeric epitope based proteins that consist of linear epitopes derived from multiple proteins or multiple variants of a protein. An inherent advantage to chimeritope vaccinogens is that they can be constructed to trigger broadly protective Ab responses. Three OspC chimeritope proteins were comparatively assessed: Chv1, Chv2 and Chv3. The Chv proteins possess the same set of 18 linear epitopes derived from 9 OspC type proteins but differ in the physical ordering of epitopes or by the presence or absence of linkers. All Chv proteins were immunogenic in mice and rats eliciting high titer Ab. Immunoblot and enzyme linked immunosorbent assays demonstrated that the Chv proteins elicit IgG that recognizes a diverse array of OspC type proteins. The panel included OspC proteins produced by N. American and European strains of the LD spirochetes. Rat anti-Chv antisera uniformly labeled intact, non-permeabilized Borreliella burgdorferi demonstrating that vaccinal Ab can bind to targets that are naturally presented on the spirochete cell surface. Vaccinal Ab also displayed potent complement dependent-Ab mediated killing activity. This study highlights the ability of OspC chimeritopes to serve as vaccinogens that trigger potentially broadly protective Ab responses. In addition to the current use of an OspC chimeritope in a canine LD vaccine, chimeritopes can serve as key components of human LD subunit vaccines.
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Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Borrelia burgdorferi , Lipoproteínas/inmunología , Vacunas contra Enfermedad de Lyme/inmunología , Enfermedad de Lyme/prevención & control , Animales , Anticuerpos Antibacterianos/inmunología , Borrelia burgdorferi/inmunología , Epítopos/inmunología , Ratones , RatasRESUMEN
BACKGROUND: Prevention of Lyme disease in dogs in North America depends on effective vaccination against infection by the tick vector-born spirochete Borrelia burgdorferi. Most vaccines effectively prevent spirochete transmission to dogs during tick feeding based on immunization with the outer-surface lipoprotein A (OspA) of B. burgdorferi. More recently, vaccines containing additional OspC protein moieties have been introduced. These are designed to enhance protection by forming a second line of defense within the vertebrate host, where OspC expression replaces OspA as the dominant surface antigen. However, supportive data for demonstration of OspC mediated protection is still lacking. Since OspA immunogenicity is of paramount importance to protection against spirochete transmission; this study was designed to compare the immunogenicity of two commercially available vaccines against the Borrelia burgdorferi OspA. We further characterized OspA antigen fractions of these vaccines with respect to their biochemical and biophysical properties. RESULTS: Two groups of beagle dogs (n = 9) were administered either: (1) a nonadjuvanted/monovalent, recombinant OspA vaccine (Recombitek® Lyme) or (2) an adjuvanted, recombinant OspA /OspC chimeric fusion vaccine (Vanguard® crLyme). The onset of the anti-OspA antibody response elicited by the nonadjuvanted/monovalent OspA vaccine was significantly earlier than that for the bivalent OspA /OspC vaccine and serum borreliacidal activity was significantly greater at all post-vaccination time points. As expected, only dogs inoculated with the bivalent OspA/OspC vaccine mounted a humoral anti-OspC response. However, only three out of nine dogs in that group had a positive response. Comparison of the OspA vaccine structures revealed that the OspA in the nonadjuvanted/monovalent vaccine was primarily in the lipidated form, eluting (SEC-HPLC) at a high molecular weight, suggestive of micelle formation. Conversely, the OspA moiety of the OspA/OspC vaccine was found to be nonlipidated and eluted as the monomeric protein. CONCLUSIONS: We hypothesize that these structural differences may account for the superior immunogenicity of the nonadjuvanted monovalent recombinant OspA vaccine in dogs over the adjuvanted OspA fraction of the OspA/OspC vaccine.
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Antígenos Bacterianos/inmunología , Antígenos de Superficie/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/inmunología , Borrelia burgdorferi/inmunología , Enfermedades de los Perros/prevención & control , Lipoproteínas/inmunología , Enfermedad de Lyme/veterinaria , Animales , Anticuerpos Antibacterianos/sangre , Formación de Anticuerpos , Antígenos Bacterianos/administración & dosificación , Antígenos de Superficie/administración & dosificación , Proteínas de la Membrana Bacteriana Externa/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/microbiología , Perros , Femenino , Inmunización , Lipoproteínas/administración & dosificación , Enfermedad de Lyme/inmunología , Enfermedad de Lyme/prevención & control , Masculino , Vacunas SintéticasRESUMEN
Borrelia burgdorferi can induce Lyme disease. Approved Lyme vaccines for horses are currently not available. In an effort to protect horses, veterinarians are using Lyme vaccines licensed for dogs. However, data to assess the response of horses to, or determine the efficacy of this off-label vaccine use are missing. Here, antibodies against outer surface protein A (OspA), OspC, and OspF were quantified in diagnostic serum submissions from horses with a history of vaccination with canine Lyme vaccines. The results suggested that many horses respond with low and often short-lasting antibody responses. Subsequently, four experimental vaccination trials were performed. First, we investigated antibody responses to three canine vaccines in B. burgdorferi-naïve horses. One killed bacterin vaccine induced antibodies against OspC. OspA antibodies were low for all three vaccines and lasted less than 16weeks. The second trial tested the impact of the vaccine dose using the OspA/OspC inducing bacterin vaccine in horses. A 2mL dose produced higher OspA and OspC antibody values than a 1mL dose. However, the antibody response again quickly declined, independent of dose. Third, the horses were vaccinated with 2 doses of a recombinant OspA vaccine. Previous vaccination and/or environmental exposure enhanced the magnitude and longevity of the OspA antibody response to about 20weeks. Last, the influence of intramuscular versus subcutaneous vaccine administration was investigated for the recombinant OspA vaccine. OspA antibody responses were not influenced by injection route. The current work highlights that commercial Lyme vaccines for dogs induce only transient antibody responses in horses which can also be of low magnitude. Protection from infection with B. burgdorferi should not be automatically assumed after vaccinating horses with Lyme vaccines for dogs.
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Anticuerpos Antibacterianos/sangre , Formación de Anticuerpos , Borrelia burgdorferi/inmunología , Enfermedades de los Caballos/prevención & control , Vacunas contra Enfermedad de Lyme/administración & dosificación , Enfermedad de Lyme/veterinaria , Animales , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Perros , Caballos , Inyecciones Intramusculares , Enfermedad de Lyme/prevención & control , Factores de Tiempo , Vacunación/métodos , Medicina Veterinaria/métodosRESUMEN
The lipoprotein OspA is produced by the Lyme disease spirochetes primarily in unfed ticks. OspA production is down-regulated by the blood meal and it is not produced in mammals except for possible transient production during late stage infection in patients with Lyme arthritis. Vaccination with OspA elicits antibody (Ab) that can target spirochetes in the tick midgut during feeding and inhibit transmission to mammals. OspA was the primary component of the human LYMErix™ vaccine. LYMErix™ was available from 1998 to 2002 but then pulled from the market due to declining sales as a result of unsubstantiated concerns about vaccination induced adverse events and poor efficacy. It was postulated that a segment of OspA that shares sequence similarity with a region in human LFA-1 and may trigger putative autoimmune events. While evidence supporting such a link has not been demonstrated, most efforts to move forward with OspA as a vaccine component have sought to eliminate this region of concern. Here we identify an OspA linear epitope localized within OspA amino acid residues 221-240 (OspA221-240) that lacks the OspA region suggested to elicit autoimmunity. A peptide consisting of residues 221-240 was immunogenic in mice. Ab raised against OspA221-240 peptide surface labeled B. burgdorferi in IFAs and displayed potent Ab mediated-complement dependent bactericidal activity. BLAST analyses identified several variants of OspA221-240 and a closely related sequence in OspB. It is our hypothesis that integration of the OspA221-240 epitope into a multivalent-OspC based chimeric epitope based vaccine antigen (chimeritope) could result in a subunit vaccine that protects against Lyme disease through synergistic mechanisms.