scholarly journals Dynamic Longitudinal Antibody Responses during Borrelia burgdorferi Infection and Antibiotic Treatment of Rhesus Macaques

2012 ◽  
Vol 19 (8) ◽  
pp. 1218-1226 ◽  
Author(s):  
Monica E. Embers ◽  
Nicole R. Hasenkampf ◽  
Mary B. Jacobs ◽  
Mario T. Philipp
Keyword(s):  
Borrelia Burgdorferi ◽  
Antibiotic Treatment ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Disease Course ◽  
Longitudinal Assessment ◽  
Multiple Points ◽  
Content Type ◽  
Treatment Responses

ABSTRACTInfection withBorrelia burgdorferielicits robust yet disparate antibody responses in infected individuals. A longitudinal assessment of antibody responses to multiple diagnostic antigens following experimental infection and treatment has not previously been reported. Our goal was to identify a combination of antigens that could indicate infection at all phases of disease and response to antibiotic treatment. Because the rhesus macaque recapitulates the hallmark signs and disease course of human Lyme disease, we examined the specific antibody responses to multiple antigens ofB. burgdorferifollowing infection of macaques. Five macaques infected with strain B31 and 12 macaques infected with strain JD1 were included in the analysis. Approximately half of these animals were treated with antibiotics at 4 to 6 months postinoculation. Antibody responses to severalB. burgdorferirecombinant antigens, including OspC, DbpA, BBK32, OspA, and OppA-2, were measured at multiple points throughout infection. We have previously shown a decline in the response to the C6 peptide following antibiotic treatment. Responses to OspA and OspC, however, were variable over time among individuals, irrespective of antibiotic treatment. Not every individual responded to BBK32, but anti-DbpA IgG levels were uniformly high and remained elevated for all animals. All responded to OppA-2, with a decline posttreatment that was slow and incomplete. This is the first demonstration ofB. burgdorferiOppA-2 antigenicity in nonhuman primates. The combination of DbpA, OspC, OspA, and OppA-2 with the C6 diagnostic peptide has the potential to detect infection throughout all disease phases.

scholarly journals Antibody Responses to a Spore Carbohydrate Antigen as a Marker of Nonfatal Inhalation Anthrax in Rhesus Macaques

2011 ◽  
Vol 18 (5) ◽  
pp. 743-748 ◽  
Author(s):  
Elke Saile ◽  
Geert-Jan Boons ◽  
Therese Buskas ◽  
Russell W. Carlson ◽  
Elmar L. Kannenberg ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Rhesus Macaques ◽  
Lethal Factor ◽  
Structural Analog ◽  
Diagnostic Value ◽  
Carbohydrate Antigen ◽  
Antibody Responses ◽  
Content Type ◽  
Aerosol Exposure ◽  
Inhalation Anthrax

ABSTRACTTheBacillus anthracisexosporium protein BclA contains an O-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (J. M. Daubenspeck et al., J. Biol. Chem. 279:30945–30953, 2004). We hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolizedB. anthracis. We evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ATS) in a group of five rhesus macaques that survived inhalation anthrax following exposure toB. anthracisAmes spores. Two of five animals (RM2 and RM3) were treated with ciprofloxacin starting at 48 hours postexposure and two (RM4 and RM5) at 72 h postexposure; one animal (RM1) was untreated. Infection was confirmed by blood culture and detection of anthrax toxin lethal factor (LF) in plasma. Anti-ATS IgG responses were determined at 14, 21, 28, and 35 days postexposure, with preexposure serum as a control. All animals, irrespective of ciprofloxacin treatment, mounted a specific, measurable anti-ATS IgG response. The earliest detectable responses were on days 14 (RM1, RM2, and RM5), 21 (RM4), and 28 (RM3). Specificity of the anti-ATS responses was demonstrated by competitive-inhibition enzyme immunoassay (CIEIA), in which a 2-fold (wt/wt) excess of carbohydrate in a bovine serum albumin (BSA) conjugate of the oligosaccharide (ATS-BSA) effected >94% inhibition, whereas a structural analog lacking the 3-hydroxy-3-methyl-butyryl moiety at the C-4" of the anthrosyl residue had no inhibition activity. These data suggest that anti-ATS antibody responses may be used to identify aerosol exposure toB. anthracisspores. The anti-ATS antibody responses were detectable during administration of ciprofloxacin.

scholarly journals Evaluation of the Impact of Codon Optimization and N-Linked Glycosylation on Functional Immunogenicity of Pfs25 DNA Vaccines Delivered byIn VivoElectroporation in Preclinical Studies in Mice

2015 ◽  
Vol 22 (9) ◽  
pp. 1013-1019 ◽  
Author(s):  
Dibyadyuti Datta ◽  
Geetha P. Bansal ◽  
Rajesh Kumar ◽  
Barry Ellefsen ◽  
Drew Hannaman ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Vaccine Development ◽  
Dna Vaccines ◽  
Codon Optimization ◽  
Antibody Responses ◽  
Transmission Blocking ◽  
Content Type ◽  
The Impact ◽  
Transmission Blocking Vaccine

ABSTRACTPlasmodium falciparumsexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application ofin vivoelectroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization,in vivoelectroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines. The results from this study demonstrate that while codon optimization andin vivoelectroporation greatly improved functional immunogenicity of Pfs25 DNA vaccines, the presence or absence of N-linked glycosylation did not significantly impact vaccine efficacy. These findings suggest that N-glycosylation of Pfs25 encoded by DNA vaccines is not detrimental to overall transmission-blocking efficacy.

scholarly journals Antibodies to Borrelia burgdorferi OspA, OspC, OspF, and C6 Antigens as Markers for Early and Late Infection in Dogs

2012 ◽  
Vol 19 (4) ◽  
pp. 527-535 ◽  
Author(s):  
Bettina Wagner ◽  
Heather Freer ◽  
Alicia Rollins ◽  
David Garcia-Tapia ◽  
Hollis N. Erb ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
The United States ◽  
Sensu Stricto ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Early Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Antibody Levels

ABSTRACTLyme disease in the United States is caused byBorrelia burgdorferisensu stricto, which is transmitted to mammals by infected ticks.Borreliaspirochetes differentially express immunogenic outer surface proteins (Osp). Our aim was to evaluate antibody responses to Osp antigens to aid the diagnosis of early infection and the management of Lyme disease. We analyzed antibody responses during the first 3 months after the experimental infection of dogs using a novel multiplex assay. Results were compared to those obtained with two commercial assays detecting C6 antigen. Multiplex analysis identified antibodies to OspC and C6 as early as 3 weeks postinfection (p.i.) and those to OspF by 5 weeks p.i. Antibodies to C6 and OspF increased throughout the study, while antibodies to OspC peaked between 7 and 11 weeks p.i. and declined thereafter. A short-term antibody response to OspA was observed in 3/8 experimentally infected dogs on day 21 p.i. Quant C6 enzyme-linked immunosorbent assay (ELISA) results matched multiplex results during the first 7 weeks p.i.; however, antibody levels subsequently declined by up to 29%. Immune responses then were analyzed in sera from 125 client-owned dogs and revealed high agreement between antibodies to OspF and C6 as robust markers for infection. Results from canine patient sera supported that OspC is an early infection marker and antibodies to OspC decline over time. The onset and decline of antibody responses toB. burgdorferiOsp antigens and C6 reflect their differential expression during infection. They provide valuable tools to determine the stage of infection, treatment outcomes, and vaccination status in dogs.

scholarly journals Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

2012 ◽  
Vol 80 (11) ◽  
pp. 3821-3827 ◽  
Author(s):  
Amma A. Semenya ◽  
JoAnn S. Sullivan ◽  
John W. Barnwell ◽  
W. Evan Secor
Keyword(s):  
Immune Responses ◽  
Schistosoma Mansoni ◽  
Malaria Infection ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Content Type ◽  
Macaque Model ◽  
Malaria Parasitemia ◽  
Intravenous Inoculation ◽  
Plasmodium Coatneyi

ABSTRACTMalaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas wherePlasmodiumandSchistosomaspecies are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infectingPlasmodiumspecies differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparumversusSchistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role ofS. mansonion malaria parasitemia and antimalarial immune responses usingPlasmodium coatneyi, a malaria species that closely resemblesP. falciparuminfection in humans. Eight rhesus macaques were exposed toS. mansonicercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans withP. falciparumthat are coinfected withS. mansoniorS. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes.

scholarly journals Experimental Infections of the Reservoir Species Peromyscus leucopus with Diverse Strains of Borrelia burgdorferi, a Lyme Disease Agent

mBio ◽  
2012 ◽  
Vol 3 (6) ◽  
Author(s):  
Elisabeth Baum ◽  
Fong Hue ◽  
Alan G. Barbour
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Peromyscus Leucopus ◽  
Antibody Responses ◽  
Full Length ◽  
Content Type ◽  
Reservoir Species ◽  
Disease Agent ◽  
Low Prevalence ◽  
Lyme Disease Agent

ABSTRACTThe rodentPeromyscus leucopusis a major natural reservoir for the Lyme disease agentBorrelia burgdorferiand a host for its vectorIxodes scapularis. At various locations in northeastern United States 10 to 15 B. burgdorferistrains coexist at different prevalences in tick populations. We asked whether representative strains of high or low prevalence differed in their infections ofP. leucopus. After 5 weeks of experimental infection of groups with each of 6 isolates, distributions and burdens of bacteria in tissues were measured by quantitative PCR, and antibodies toB. burgdorferiwere evaluated by immunoblotting and protein microarray. All groups of animals were infected in their joints, ears, tails, and hearts, but overall spirochete burdens were lower in animals infected with low-prevalence strains. Animals were similar regardless of the infecting isolate in their levels of antibodies to whole cells, FlaB, BmpA, and DbpB proteins, and the conserved N-terminal region of the serotype-defining OspC proteins. But there were strain-specific antibody responses to full-length OspC and to plasmid-encoded VlsE, BBK07, and BBK12 proteins. Sequencing of additional VlsE genes revealed substantial diversity within some pairs of strains but near-identical sequences within other pairs, which otherwise differed in theirospCalleles. The presence or absence of full-length bbk07 and bbk12 genes accounted for the differences in antibody responses. We propose that forB. burgdorferi, there is selection in reservoir species for (i) sequence diversity, as for OspC and VlsE, and (ii) the presence or absence of polymorphisms, as for BBK07 and BBK12.IMPORTANCEHumans are dead-end hosts forBorreliaagents of Lyme disease (LD), and, thus, irrelevant for the pathogens’ maintenance. Many reports of human cases and laboratory mouse infections exist, but less is known about infection and immunity in natural reservoirs, such as the rodentPeromyscus leucopus. We observed that high- and low-prevalence strains ofBorrelia burgdorferiwere capable of infectingP. leucopusbut elicited different patterns of antibody responses. Antibody reactivities to the VlsE protein were as type-specific as previously characterized reactivities to serotype-defining OspC proteins. In addition, the low-prevalence strains lacked full-length genes for two proteins that (i) are encoded by a virulence-associated plasmid in some high-prevalence strains and (ii) LD patients and field-captured rodents commonly have antibodies to. Immune selection against these genes may have led to null phenotype lineages that can infect otherwise immune hosts but at the cost of reduced fitness and lower prevalence.

scholarly journals Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. e29914 ◽  
Author(s):  
Monica E. Embers ◽  
Stephen W. Barthold ◽  
Juan T. Borda ◽  
Lisa Bowers ◽  
Lara Doyle ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Antibiotic Treatment ◽  
Rhesus Macaques ◽  
Disseminated Infection

scholarly journals Correction: Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
Author(s):  
Monica E. Embers ◽  
Stephen W. Barthold ◽  
Juan T. Borda ◽  
Lisa Bowers ◽  
Lara Doyle ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Antibiotic Treatment ◽  
Rhesus Macaques ◽  
Disseminated Infection

scholarly journals Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

2014 ◽  
Vol 21 (6) ◽  
pp. 838-846 ◽  
Author(s):  
Elisabeth Baum ◽  
Deborah A. Grosenbaugh ◽  
Alan G. Barbour
Keyword(s):  
Borrelia Burgdorferi ◽  
Binding Protein ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Domestic Dog ◽  
Beagle Dogs ◽  
Effective Population ◽  
Content Type ◽  
Immunogenic Proteins ◽  
Antibody Levels

ABSTRACTLyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agentBorrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses toB. burgdorferiinfection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected withB. burgdorferithrough tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encodedB. burgdorferiproteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC.

scholarly journals A Novel Multivalent OspA Vaccine against Lyme Borreliosis Is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi Sensu Lato

2014 ◽  
Vol 21 (11) ◽  
pp. 1490-1499 ◽  
Author(s):  
Nina Wressnigg ◽  
P. Noel Barrett ◽  
Eva-Maria Pöllabauer ◽  
Maria O'Rourke ◽  
Daniel Portsmouth ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Lyme Borreliosis ◽  
Adult Population ◽  
Antibody Responses ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Enzyme Linked Immunosorbent Assay ◽  
Limited Information ◽  
Surface Binding ◽  
Double Blind ◽  
Content Type

ABSTRACTLyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection withBorrelia burgdorferisensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previousB. burgdorferi sensu latoinfection. The participants received three monthly priming immunizations with either 30 μg or 60 μg alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected withB. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.)

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