Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers

Abstract Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emerg...

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Veröffentlicht in:Journal of animal science 2020-06, Vol.98 (6), p.1-6
Hauptverfasser: Curtis, Andrew K, Reif, Kathryn E, Kleinhenz, Michael D, Martin, Miriam S, Skinner, Brandt, Kelly, Sean M, Jones, Douglas E, Schaut, Robert G, Reppert, Emily J, Montgomery, Shawnee R, Narasimhan, Balaji, Anantatat, Tippawan, Jaberi-Douraki, Majid, Coetzee, Johann F
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container_end_page 6
container_issue 6
container_start_page 1
container_title Journal of animal science
container_volume 98
creator Curtis, Andrew K
Reif, Kathryn E
Kleinhenz, Michael D
Martin, Miriam S
Skinner, Brandt
Kelly, Sean M
Jones, Douglas E
Schaut, Robert G
Reppert, Emily J
Montgomery, Shawnee R
Narasimhan, Balaji
Anantatat, Tippawan
Jaberi-Douraki, Majid
Coetzee, Johann F
description Abstract Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11 to 12 wk, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale, a major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing a combination of 2 different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty-one months post-implantation, calves were challenged intravenously with A. marginale stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed-effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long-lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct.
doi_str_mv 10.1093/jas/skz392
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Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11 to 12 wk, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale, a major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing a combination of 2 different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty-one months post-implantation, calves were challenged intravenously with A. marginale stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed-effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long-lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct.</description><identifier>ISSN: 0021-8812</identifier><identifier>EISSN: 1525-3163</identifier><identifier>DOI: 10.1093/jas/skz392</identifier><identifier>PMID: 31889177</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Active control ; Adjuvants ; Anaplasma marginale ; Anaplasmosis ; Anaplasmosis - immunology ; Anaplasmosis - microbiology ; Anaplasmosis - prevention &amp; control ; Animals ; Antibiotics ; Antigens ; Antimicrobial resistance ; Bacteremia ; Bacterial Vaccines - administration &amp; dosage ; Bacterial Vaccines - immunology ; Biodegradability ; Biodegradation ; Calves ; Cattle ; Cattle Diseases - prevention &amp; control ; Cell size ; Chlortetracycline ; Control programs ; Delayed-Action Preparations ; Dextran ; Diethylaminoethyl dextran ; Disease transmission ; Drug delivery systems ; Drug Implants ; Ear ; Fever ; Health risks ; Human papillomavirus ; Immune response ; Immune system ; Immunization ; Implantation ; Implants ; Infections ; Male ; Medicated feeds ; Polyanhydrides ; Priming ; Rapid Communication ; Rods ; Studies ; Vaccines</subject><ispartof>Journal of animal science, 2020-06, Vol.98 (6), p.1-6</ispartof><rights>The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. 2019</rights><rights>The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.</rights><rights>Copyright Oxford University Press Jun 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-d8f9ba03588ea1931ad7b87534c57384eabe20ce0c61180e0c01fc3924ae6a653</citedby><cites>FETCH-LOGICAL-c436t-d8f9ba03588ea1931ad7b87534c57384eabe20ce0c61180e0c01fc3924ae6a653</cites><orcidid>0000-0003-1802-3991 ; 0000-0001-9453-3657</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271671/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271671/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1578,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31889177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Curtis, Andrew K</creatorcontrib><creatorcontrib>Reif, Kathryn E</creatorcontrib><creatorcontrib>Kleinhenz, Michael D</creatorcontrib><creatorcontrib>Martin, Miriam S</creatorcontrib><creatorcontrib>Skinner, Brandt</creatorcontrib><creatorcontrib>Kelly, Sean M</creatorcontrib><creatorcontrib>Jones, Douglas E</creatorcontrib><creatorcontrib>Schaut, Robert G</creatorcontrib><creatorcontrib>Reppert, Emily J</creatorcontrib><creatorcontrib>Montgomery, Shawnee R</creatorcontrib><creatorcontrib>Narasimhan, Balaji</creatorcontrib><creatorcontrib>Anantatat, Tippawan</creatorcontrib><creatorcontrib>Jaberi-Douraki, Majid</creatorcontrib><creatorcontrib>Coetzee, Johann F</creatorcontrib><title>Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers</title><title>Journal of animal science</title><addtitle>J Anim Sci</addtitle><description>Abstract Bovine anaplasmosis is the most prevalent tick-transmitted disease of cattle worldwide and a major obstacle to profitable beef production. Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11 to 12 wk, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale, a major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing a combination of 2 different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty-one months post-implantation, calves were challenged intravenously with A. marginale stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed-effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long-lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct.</description><subject>Active control</subject><subject>Adjuvants</subject><subject>Anaplasma marginale</subject><subject>Anaplasmosis</subject><subject>Anaplasmosis - immunology</subject><subject>Anaplasmosis - microbiology</subject><subject>Anaplasmosis - prevention &amp; control</subject><subject>Animals</subject><subject>Antibiotics</subject><subject>Antigens</subject><subject>Antimicrobial resistance</subject><subject>Bacteremia</subject><subject>Bacterial Vaccines - administration &amp; dosage</subject><subject>Bacterial Vaccines - immunology</subject><subject>Biodegradability</subject><subject>Biodegradation</subject><subject>Calves</subject><subject>Cattle</subject><subject>Cattle Diseases - prevention &amp; control</subject><subject>Cell size</subject><subject>Chlortetracycline</subject><subject>Control programs</subject><subject>Delayed-Action Preparations</subject><subject>Dextran</subject><subject>Diethylaminoethyl dextran</subject><subject>Disease transmission</subject><subject>Drug delivery systems</subject><subject>Drug Implants</subject><subject>Ear</subject><subject>Fever</subject><subject>Health risks</subject><subject>Human papillomavirus</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Implantation</subject><subject>Implants</subject><subject>Infections</subject><subject>Male</subject><subject>Medicated feeds</subject><subject>Polyanhydrides</subject><subject>Priming</subject><subject>Rapid Communication</subject><subject>Rods</subject><subject>Studies</subject><subject>Vaccines</subject><issn>0021-8812</issn><issn>1525-3163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kV-L1TAQxYMo7vXqix9AArIgQnczSdukL4LsHxUWfNE3IUxzp5pr29SkvbB-erN2XdSHhcBA5sfhnDmMPQdxAqJRp3tMp-n7T9XIB2wDlawKBbV6yDZCSCiMAXnEnqS0FwJk1VSP2ZECYxrQesO-nNOB-jANNM48dBx5Wlq3zDhSWBInjNwPU495Owe-o94fKHIc88P8nYaQfOIHdM6P9BtBH695moliesoeddgnenY7t-zz5cWns_fF1cd3H87eXhWuVPVc7EzXtChUZQwhNApwp1ujK1W6SitTErYkhSPhagAj8hTQuRy3RKqxrtSWvVl1p6UdaOdyloi9naIfMF7bgN7-uxn9N_s1HKyWGmoNWeDVrUAMPxZKsx18ctT36xmsVDcXVRpkRl_-h-7DEsccz8pSVrWEJpvestcr5WJIKVJ3ZwaEvSnN5tLsWlqGX_xt_w7901IGjlcgLNN9Qr8AM26hrw</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Curtis, Andrew K</creator><creator>Reif, Kathryn E</creator><creator>Kleinhenz, Michael D</creator><creator>Martin, Miriam S</creator><creator>Skinner, Brandt</creator><creator>Kelly, Sean M</creator><creator>Jones, Douglas E</creator><creator>Schaut, Robert G</creator><creator>Reppert, Emily J</creator><creator>Montgomery, Shawnee R</creator><creator>Narasimhan, Balaji</creator><creator>Anantatat, Tippawan</creator><creator>Jaberi-Douraki, Majid</creator><creator>Coetzee, Johann F</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RQ</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>S0X</scope><scope>U9A</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1802-3991</orcidid><orcidid>https://orcid.org/0000-0001-9453-3657</orcidid></search><sort><creationdate>20200601</creationdate><title>Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers</title><author>Curtis, Andrew K ; Reif, Kathryn E ; Kleinhenz, Michael D ; Martin, Miriam S ; Skinner, Brandt ; Kelly, Sean M ; Jones, Douglas E ; Schaut, Robert G ; Reppert, Emily J ; Montgomery, Shawnee R ; Narasimhan, Balaji ; Anantatat, Tippawan ; Jaberi-Douraki, Majid ; Coetzee, Johann F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-d8f9ba03588ea1931ad7b87534c57384eabe20ce0c61180e0c01fc3924ae6a653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Active control</topic><topic>Adjuvants</topic><topic>Anaplasma marginale</topic><topic>Anaplasmosis</topic><topic>Anaplasmosis - immunology</topic><topic>Anaplasmosis - microbiology</topic><topic>Anaplasmosis - prevention &amp; control</topic><topic>Animals</topic><topic>Antibiotics</topic><topic>Antigens</topic><topic>Antimicrobial resistance</topic><topic>Bacteremia</topic><topic>Bacterial Vaccines - administration &amp; dosage</topic><topic>Bacterial Vaccines - immunology</topic><topic>Biodegradability</topic><topic>Biodegradation</topic><topic>Calves</topic><topic>Cattle</topic><topic>Cattle Diseases - prevention &amp; 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Use of chlortetracycline-medicated feed to control active anaplasmosis infections during the vector season has raised concerns about the potential emergence of antimicrobial resistance in bacteria that may pose a risk to human health. Furthermore, the absence of effectiveness data for a commercially available, conditionally licensed anaplasmosis vaccine is a major impediment to implementing anaplasmosis control programs. The primary objective of this study was to develop a single-dose vaccine delivery platform to produce long-lasting protective immunity against anaplasmosis infections. Twelve Holstein steers, aged 11 to 12 wk, were administered a novel 3-stage, single-dose vaccine against Anaplasma marginale, a major surface protein 1a. The vaccine consisted of a soluble vaccine administered subcutaneously (s.c.) for immune priming, a vaccine depot of a biodegradable polyanhydride rod with intermediate slow release of the vaccine for boosting immune response, and an immune-isolated vaccine platform for extended antigen release (VPEAR implant) deposited s.c. in the ear. Six calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing a combination of 2 different adjuvants, diethylaminoethyl (DEAE)-Dextran and Quil-A (Group A). The remaining 6 calves were randomly assigned to 2 vaccine constructs (n = 3) that featured rods and implants containing the same adjuvant (either DEAE-Dextran or Quil A) (Group B). Twenty-one months post-implantation, calves were challenged intravenously with A. marginale stabilate and were monitored weekly for signs of fever, decreased packed cell volume (PCV) and bacteremia. Data were analyzed using a mixed-effects model and chi-squared tests (SAS v9.04.01, SAS Institute, Cary, NC). Calves in Group A had higher PCV than calves in Group B (P = 0.006) at day 35 post-infection. Calves in Group A were less likely to require antibiotic intervention compared with calves in Group B (P = 0.014). Results indicate that calves exhibited diminished clinical signs of anaplasmosis when antigen was delivered with a combination of adjuvants as opposed to a single adjuvant. This demonstrates the feasibility of providing long-lasting protection against clinical bovine anaplasmosis infections using a subcutaneous ear implant vaccine construct.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>31889177</pmid><doi>10.1093/jas/skz392</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0003-1802-3991</orcidid><orcidid>https://orcid.org/0000-0001-9453-3657</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0021-8812
ispartof Journal of animal science, 2020-06, Vol.98 (6), p.1-6
issn 0021-8812
1525-3163
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7271671
source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Active control
Adjuvants
Anaplasma marginale
Anaplasmosis
Anaplasmosis - immunology
Anaplasmosis - microbiology
Anaplasmosis - prevention & control
Animals
Antibiotics
Antigens
Antimicrobial resistance
Bacteremia
Bacterial Vaccines - administration & dosage
Bacterial Vaccines - immunology
Biodegradability
Biodegradation
Calves
Cattle
Cattle Diseases - prevention & control
Cell size
Chlortetracycline
Control programs
Delayed-Action Preparations
Dextran
Diethylaminoethyl dextran
Disease transmission
Drug delivery systems
Drug Implants
Ear
Fever
Health risks
Human papillomavirus
Immune response
Immune system
Immunization
Implantation
Implants
Infections
Male
Medicated feeds
Polyanhydrides
Priming
Rapid Communication
Rods
Studies
Vaccines
title Development of a subcutaneous ear implant to deliver an anaplasmosis vaccine to dairy steers
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