Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71

Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis....

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Veröffentlicht in:Vaccine 2008-02, Vol.26 (7), p.891-898
Hauptverfasser: Chen, Hsiao-Ling, Wang, Li-Chung, Chang, Chi-Hsuan, Yen, Chih-Ching, Cheng, Winston T.K, Wu, Shinn-Chih, Hung, Che-Ming, Kuo, Meng-Fu, Chen, Chuan-Mu
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container_issue 7
container_start_page 891
container_title Vaccine
container_volume 26
creator Chen, Hsiao-Ling
Wang, Li-Chung
Chang, Chi-Hsuan
Yen, Chih-Ching
Cheng, Winston T.K
Wu, Shinn-Chih
Hung, Che-Ming
Kuo, Meng-Fu
Chen, Chuan-Mu
description Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.
doi_str_mv 10.1016/j.vaccine.2007.12.013
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Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2007.12.013</identifier><identifier>PMID: 18207613</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animal models ; Animals ; Animals, Newborn ; Antimicrobial agents ; Antiviral activity ; Antiviral Agents - immunology ; Antiviral Agents - metabolism ; Biological and medical sciences ; Body Weight ; Child, Preschool ; Cytomegalovirus ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Enterovirus ; Enterovirus - isolation &amp; purification ; Enterovirus - pathogenicity ; Enterovirus 71 ; Enterovirus Infections - mortality ; Enterovirus Infections - prevention &amp; control ; Enterovirus Infections - virology ; Female ; Females ; Fundamental and applied biological sciences. Psychology ; HIV ; Human immunodeficiency virus ; Humans ; Infant, Newborn ; Infections ; Lactalbumin - genetics ; Lactalbumin - immunology ; Lactalbumin - metabolism ; Lactation ; Lactoferrin - genetics ; Lactoferrin - immunology ; Lactoferrin - metabolism ; Mammals ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Microbiology ; Milk ; Milk - chemistry ; Milk - metabolism ; Miscellaneous ; Mortality ; Neonatal viral infection ; Porcine lactoferrin ; Recombinant Proteins - genetics ; Recombinant Proteins - immunology ; Recombinant Proteins - metabolism ; Rodents ; Survival ; Swine ; Transgenic animals ; Transgenic mice ; Virology ; Yeast</subject><ispartof>Vaccine, 2008-02, Vol.26 (7), p.891-898</ispartof><rights>Elsevier Ltd</rights><rights>2007 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Limited Feb 13, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</citedby><cites>FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1558808763?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20043503$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18207613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hsiao-Ling</creatorcontrib><creatorcontrib>Wang, Li-Chung</creatorcontrib><creatorcontrib>Chang, Chi-Hsuan</creatorcontrib><creatorcontrib>Yen, Chih-Ching</creatorcontrib><creatorcontrib>Cheng, Winston T.K</creatorcontrib><creatorcontrib>Wu, Shinn-Chih</creatorcontrib><creatorcontrib>Hung, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Meng-Fu</creatorcontrib><creatorcontrib>Chen, Chuan-Mu</creatorcontrib><title>Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Summary The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</description><subject>Allergy and Immunology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antimicrobial agents</subject><subject>Antiviral activity</subject><subject>Antiviral Agents - immunology</subject><subject>Antiviral Agents - metabolism</subject><subject>Biological and medical sciences</subject><subject>Body Weight</subject><subject>Child, Preschool</subject><subject>Cytomegalovirus</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Enterovirus</subject><subject>Enterovirus - isolation &amp; purification</subject><subject>Enterovirus - pathogenicity</subject><subject>Enterovirus 71</subject><subject>Enterovirus Infections - mortality</subject><subject>Enterovirus Infections - prevention &amp; control</subject><subject>Enterovirus Infections - virology</subject><subject>Female</subject><subject>Females</subject><subject>Fundamental and applied biological sciences. 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Wang, Li-Chung ; Chang, Chi-Hsuan ; Yen, Chih-Ching ; Cheng, Winston T.K ; Wu, Shinn-Chih ; Hung, Che-Ming ; Kuo, Meng-Fu ; Chen, Chuan-Mu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-73e00412ffbc892efa2815254a9777dc527463377b91ae7a1d45f42be251881f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Allergy and Immunology</topic><topic>Animal models</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antimicrobial agents</topic><topic>Antiviral activity</topic><topic>Antiviral Agents - immunology</topic><topic>Antiviral Agents - metabolism</topic><topic>Biological and medical sciences</topic><topic>Body Weight</topic><topic>Child, Preschool</topic><topic>Cytomegalovirus</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Enterovirus</topic><topic>Enterovirus - isolation &amp; purification</topic><topic>Enterovirus - pathogenicity</topic><topic>Enterovirus 71</topic><topic>Enterovirus Infections - mortality</topic><topic>Enterovirus Infections - prevention &amp; control</topic><topic>Enterovirus Infections - virology</topic><topic>Female</topic><topic>Females</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Infections</topic><topic>Lactalbumin - genetics</topic><topic>Lactalbumin - immunology</topic><topic>Lactalbumin - metabolism</topic><topic>Lactation</topic><topic>Lactoferrin - genetics</topic><topic>Lactoferrin - immunology</topic><topic>Lactoferrin - metabolism</topic><topic>Mammals</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Microbiology</topic><topic>Milk</topic><topic>Milk - chemistry</topic><topic>Milk - metabolism</topic><topic>Miscellaneous</topic><topic>Mortality</topic><topic>Neonatal viral infection</topic><topic>Porcine lactoferrin</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - immunology</topic><topic>Recombinant Proteins - metabolism</topic><topic>Rodents</topic><topic>Survival</topic><topic>Swine</topic><topic>Transgenic animals</topic><topic>Transgenic mice</topic><topic>Virology</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hsiao-Ling</creatorcontrib><creatorcontrib>Wang, Li-Chung</creatorcontrib><creatorcontrib>Chang, Chi-Hsuan</creatorcontrib><creatorcontrib>Yen, Chih-Ching</creatorcontrib><creatorcontrib>Cheng, Winston T.K</creatorcontrib><creatorcontrib>Wu, Shinn-Chih</creatorcontrib><creatorcontrib>Hung, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Meng-Fu</creatorcontrib><creatorcontrib>Chen, Chuan-Mu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing &amp; 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Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (αLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>18207613</pmid><doi>10.1016/j.vaccine.2007.12.013</doi><tpages>8</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals Complete; ProQuest Central UK/Ireland
subjects Allergy and Immunology
Animal models
Animals
Animals, Newborn
Antimicrobial agents
Antiviral activity
Antiviral Agents - immunology
Antiviral Agents - metabolism
Biological and medical sciences
Body Weight
Child, Preschool
Cytomegalovirus
Deoxyribonucleic acid
Disease Models, Animal
DNA
Enterovirus
Enterovirus - isolation & purification
Enterovirus - pathogenicity
Enterovirus 71
Enterovirus Infections - mortality
Enterovirus Infections - prevention & control
Enterovirus Infections - virology
Female
Females
Fundamental and applied biological sciences. Psychology
HIV
Human immunodeficiency virus
Humans
Infant, Newborn
Infections
Lactalbumin - genetics
Lactalbumin - immunology
Lactalbumin - metabolism
Lactation
Lactoferrin - genetics
Lactoferrin - immunology
Lactoferrin - metabolism
Mammals
Mice
Mice, Inbred BALB C
Mice, Transgenic
Microbiology
Milk
Milk - chemistry
Milk - metabolism
Miscellaneous
Mortality
Neonatal viral infection
Porcine lactoferrin
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Recombinant Proteins - metabolism
Rodents
Survival
Swine
Transgenic animals
Transgenic mice
Virology
Yeast
title Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71
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