Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model
Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation...
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| Veröffentlicht in: | Journal of pediatric surgery 2025-01, Vol.60 (1), p.161956, Article 161956 |
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| creator | Moskowitzova, Kamila Naus, Abbie E. Tsikis, Savas T. Dang, Tanya T. Lin, Shuqi B. Zurakowski, David Fauza, Dario O. |
| description | Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation via the placenta. We investigated whether transamniotic mRNA delivery could be a viable strategy for perinatal CMV immunization, first utilizing a rodent model.
Pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 103) of either human CMV (hCMV) envelope glycoprotein B (hCMV-gB) antigen mRNA encapsulated in lipopolyplex (mRNA group; n = 56), or of the same lipopolyplex without mRNA (controls; n = 47) on gestational day 17 (E17; term = E21-22). Term placentas were screened for host production of hCMV-gB by protein immunoblotting. Serum hCMV-gB IgG antibodies were measured at term, and 7 (P7) and 14 (P14) days after birth by ELISA.
Overall fetal/neonatal survival was 86 % (89/103). Immunoblotting showed hCMV-gB presence in term mRNA placentas (p = 0.008 vs. controls). No hCMV-gB IgG was detected in the serum of term fetuses (4 days following transamniotic delivery). However, significantly increased serum hCMV-gB IgG levels were present in mRNA pups at P7 (p = 0.008) and P14 (p = 0.006) when controlled by mRNA-free injections (11–19 days after transamniotic administration).
Transamniotic fetal mRNA delivery of a human cytomegalovirus antigen can induce a humoral immune response extending into the neonatal period in a healthy rat model. Fetal mRNA vaccination via the minimally invasive transamniotic route may become a practical strategy for the prevention of perinatal infections.
N/A (animal and laboratory study).
Animal and Laboratory Study. |
| doi_str_mv | 10.1016/j.jpedsurg.2024.161956 |
| format | Article |
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Pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 103) of either human CMV (hCMV) envelope glycoprotein B (hCMV-gB) antigen mRNA encapsulated in lipopolyplex (mRNA group; n = 56), or of the same lipopolyplex without mRNA (controls; n = 47) on gestational day 17 (E17; term = E21-22). Term placentas were screened for host production of hCMV-gB by protein immunoblotting. Serum hCMV-gB IgG antibodies were measured at term, and 7 (P7) and 14 (P14) days after birth by ELISA.
Overall fetal/neonatal survival was 86 % (89/103). Immunoblotting showed hCMV-gB presence in term mRNA placentas (p = 0.008 vs. controls). No hCMV-gB IgG was detected in the serum of term fetuses (4 days following transamniotic delivery). However, significantly increased serum hCMV-gB IgG levels were present in mRNA pups at P7 (p = 0.008) and P14 (p = 0.006) when controlled by mRNA-free injections (11–19 days after transamniotic administration).
Transamniotic fetal mRNA delivery of a human cytomegalovirus antigen can induce a humoral immune response extending into the neonatal period in a healthy rat model. Fetal mRNA vaccination via the minimally invasive transamniotic route may become a practical strategy for the prevention of perinatal infections.
N/A (animal and laboratory study).
Animal and Laboratory Study.</description><identifier>ISSN: 0022-3468</identifier><identifier>ISSN: 1531-5037</identifier><identifier>EISSN: 1531-5037</identifier><identifier>DOI: 10.1016/j.jpedsurg.2024.161956</identifier><identifier>PMID: 39389880</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Amnion ; Amniotic Fluid - virology ; Animals ; Animals, Newborn ; Antibodies, Viral - blood ; Cytomegalovirus ; Cytomegalovirus - genetics ; Cytomegalovirus - immunology ; Cytomegalovirus Infections - prevention & control ; Cytomegalovirus Vaccines - administration & dosage ; Cytomegalovirus Vaccines - immunology ; Disease Models, Animal ; Female ; Fetal mRNA immunization ; Fetus - virology ; Humans ; mRNA ; Pregnancy ; Pregnancy Complications, Infectious - prevention & control ; Pregnancy Complications, Infectious - virology ; Rats ; Rats, Sprague-Dawley ; RNA, Messenger - administration & dosage ; TRANAT ; Transamniotic fetal immunization ; Transamniotic mRNA therapy ; Transamniotic nucleic acid therapy ; Vaccination - methods</subject><ispartof>Journal of pediatric surgery, 2025-01, Vol.60 (1), p.161956, Article 161956</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1600-c80ea99a88193abe09ed2b96418cf75e16aa7e2f1ee86e4b3c42480f0bcc21273</cites><orcidid>0000-0002-0679-0125</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39389880$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moskowitzova, Kamila</creatorcontrib><creatorcontrib>Naus, Abbie E.</creatorcontrib><creatorcontrib>Tsikis, Savas T.</creatorcontrib><creatorcontrib>Dang, Tanya T.</creatorcontrib><creatorcontrib>Lin, Shuqi B.</creatorcontrib><creatorcontrib>Zurakowski, David</creatorcontrib><creatorcontrib>Fauza, Dario O.</creatorcontrib><title>Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model</title><title>Journal of pediatric surgery</title><addtitle>J Pediatr Surg</addtitle><description>Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation via the placenta. We investigated whether transamniotic mRNA delivery could be a viable strategy for perinatal CMV immunization, first utilizing a rodent model.
Pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 103) of either human CMV (hCMV) envelope glycoprotein B (hCMV-gB) antigen mRNA encapsulated in lipopolyplex (mRNA group; n = 56), or of the same lipopolyplex without mRNA (controls; n = 47) on gestational day 17 (E17; term = E21-22). Term placentas were screened for host production of hCMV-gB by protein immunoblotting. Serum hCMV-gB IgG antibodies were measured at term, and 7 (P7) and 14 (P14) days after birth by ELISA.
Overall fetal/neonatal survival was 86 % (89/103). Immunoblotting showed hCMV-gB presence in term mRNA placentas (p = 0.008 vs. controls). No hCMV-gB IgG was detected in the serum of term fetuses (4 days following transamniotic delivery). However, significantly increased serum hCMV-gB IgG levels were present in mRNA pups at P7 (p = 0.008) and P14 (p = 0.006) when controlled by mRNA-free injections (11–19 days after transamniotic administration).
Transamniotic fetal mRNA delivery of a human cytomegalovirus antigen can induce a humoral immune response extending into the neonatal period in a healthy rat model. Fetal mRNA vaccination via the minimally invasive transamniotic route may become a practical strategy for the prevention of perinatal infections.
N/A (animal and laboratory study).
Animal and Laboratory Study.</description><subject>Amnion</subject><subject>Amniotic Fluid - virology</subject><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Antibodies, Viral - blood</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - genetics</subject><subject>Cytomegalovirus - immunology</subject><subject>Cytomegalovirus Infections - prevention & control</subject><subject>Cytomegalovirus Vaccines - administration & dosage</subject><subject>Cytomegalovirus Vaccines - immunology</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fetal mRNA immunization</subject><subject>Fetus - virology</subject><subject>Humans</subject><subject>mRNA</subject><subject>Pregnancy</subject><subject>Pregnancy Complications, Infectious - prevention & control</subject><subject>Pregnancy Complications, Infectious - virology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA, Messenger - administration & dosage</subject><subject>TRANAT</subject><subject>Transamniotic fetal immunization</subject><subject>Transamniotic mRNA therapy</subject><subject>Transamniotic nucleic acid therapy</subject><subject>Vaccination - methods</subject><issn>0022-3468</issn><issn>1531-5037</issn><issn>1531-5037</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi0EokvhL1Q-cskythPH4cRqobRS-VBVuFqOM1l5FduLnaxYfj1ZpeXKaUaj553RPIRcMVgzYPLdfr0_YJentFtz4OWaSdZU8hlZsUqwogJRPycrAM4LUUp1QV7lvAeYx8BekgvRCNUoBSvy-zsmF8xoBvrTWHtuXQy0PdGHZEI2Prg4Okuv8Yz4-68b-hEHd8R0ek9vvZ-C-7NENjvjQh7pzeRNoNvTGD3uzBCPLk2ZukANvY8dhpF-mcvwmrzozZDxzWO9JD-uPz1sb4q7b59vt5u7wjIJUFgFaJrGKMUaYVqEBjveNrJkyvZ1hUwaUyPvGaKSWLbClrxU0ENrLWe8Fpfk7bL3kOKvCfOovcsWh8EEjFPWgrGqAlaDnFG5oDbFnBP2-pCcN-mkGeizdb3XT9b12bperM_Bq8cbU-ux-xd70jwDHxYA50-PDpPO1mGw2LmEdtRddP-78Rf16phj</recordid><startdate>202501</startdate><enddate>202501</enddate><creator>Moskowitzova, Kamila</creator><creator>Naus, Abbie E.</creator><creator>Tsikis, Savas T.</creator><creator>Dang, Tanya T.</creator><creator>Lin, Shuqi B.</creator><creator>Zurakowski, David</creator><creator>Fauza, Dario O.</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0002-0679-0125</orcidid></search><sort><creationdate>202501</creationdate><title>Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model</title><author>Moskowitzova, Kamila ; Naus, Abbie E. ; Tsikis, Savas T. ; Dang, Tanya T. ; Lin, Shuqi B. ; Zurakowski, David ; Fauza, Dario O.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1600-c80ea99a88193abe09ed2b96418cf75e16aa7e2f1ee86e4b3c42480f0bcc21273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Amnion</topic><topic>Amniotic Fluid - virology</topic><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Antibodies, Viral - blood</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus - genetics</topic><topic>Cytomegalovirus - immunology</topic><topic>Cytomegalovirus Infections - prevention & control</topic><topic>Cytomegalovirus Vaccines - administration & dosage</topic><topic>Cytomegalovirus Vaccines - immunology</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Fetal mRNA immunization</topic><topic>Fetus - virology</topic><topic>Humans</topic><topic>mRNA</topic><topic>Pregnancy</topic><topic>Pregnancy Complications, Infectious - prevention & control</topic><topic>Pregnancy Complications, Infectious - virology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA, Messenger - administration & dosage</topic><topic>TRANAT</topic><topic>Transamniotic fetal immunization</topic><topic>Transamniotic mRNA therapy</topic><topic>Transamniotic nucleic acid therapy</topic><topic>Vaccination - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moskowitzova, Kamila</creatorcontrib><creatorcontrib>Naus, Abbie E.</creatorcontrib><creatorcontrib>Tsikis, Savas T.</creatorcontrib><creatorcontrib>Dang, Tanya T.</creatorcontrib><creatorcontrib>Lin, Shuqi B.</creatorcontrib><creatorcontrib>Zurakowski, David</creatorcontrib><creatorcontrib>Fauza, Dario O.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pediatric surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moskowitzova, Kamila</au><au>Naus, Abbie E.</au><au>Tsikis, Savas T.</au><au>Dang, Tanya T.</au><au>Lin, Shuqi B.</au><au>Zurakowski, David</au><au>Fauza, Dario O.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model</atitle><jtitle>Journal of pediatric surgery</jtitle><addtitle>J Pediatr Surg</addtitle><date>2025-01</date><risdate>2025</risdate><volume>60</volume><issue>1</issue><spage>161956</spage><pages>161956-</pages><artnum>161956</artnum><issn>0022-3468</issn><issn>1531-5037</issn><eissn>1531-5037</eissn><abstract>Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation via the placenta. We investigated whether transamniotic mRNA delivery could be a viable strategy for perinatal CMV immunization, first utilizing a rodent model.
Pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 103) of either human CMV (hCMV) envelope glycoprotein B (hCMV-gB) antigen mRNA encapsulated in lipopolyplex (mRNA group; n = 56), or of the same lipopolyplex without mRNA (controls; n = 47) on gestational day 17 (E17; term = E21-22). Term placentas were screened for host production of hCMV-gB by protein immunoblotting. Serum hCMV-gB IgG antibodies were measured at term, and 7 (P7) and 14 (P14) days after birth by ELISA.
Overall fetal/neonatal survival was 86 % (89/103). Immunoblotting showed hCMV-gB presence in term mRNA placentas (p = 0.008 vs. controls). No hCMV-gB IgG was detected in the serum of term fetuses (4 days following transamniotic delivery). However, significantly increased serum hCMV-gB IgG levels were present in mRNA pups at P7 (p = 0.008) and P14 (p = 0.006) when controlled by mRNA-free injections (11–19 days after transamniotic administration).
Transamniotic fetal mRNA delivery of a human cytomegalovirus antigen can induce a humoral immune response extending into the neonatal period in a healthy rat model. Fetal mRNA vaccination via the minimally invasive transamniotic route may become a practical strategy for the prevention of perinatal infections.
N/A (animal and laboratory study).
Animal and Laboratory Study.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39389880</pmid><doi>10.1016/j.jpedsurg.2024.161956</doi><orcidid>https://orcid.org/0000-0002-0679-0125</orcidid></addata></record> |
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| subjects | Amnion Amniotic Fluid - virology Animals Animals, Newborn Antibodies, Viral - blood Cytomegalovirus Cytomegalovirus - genetics Cytomegalovirus - immunology Cytomegalovirus Infections - prevention & control Cytomegalovirus Vaccines - administration & dosage Cytomegalovirus Vaccines - immunology Disease Models, Animal Female Fetal mRNA immunization Fetus - virology Humans mRNA Pregnancy Pregnancy Complications, Infectious - prevention & control Pregnancy Complications, Infectious - virology Rats Rats, Sprague-Dawley RNA, Messenger - administration & dosage TRANAT Transamniotic fetal immunization Transamniotic mRNA therapy Transamniotic nucleic acid therapy Vaccination - methods |
| title | Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model |
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