Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport
Pregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2017/7373196 |
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| _version_ | 1832549353387982848 |
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| author | Yanqun Xu Iftekhar Mahmood Lilin Zhong Pei Zhang Evi B. Struble |
| author_facet | Yanqun Xu Iftekhar Mahmood Lilin Zhong Pei Zhang Evi B. Struble |
| author_sort | Yanqun Xu |
| collection | DOAJ |
| description | Pregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach for protecting the mother and the neonate from infections remains a high priority. Our work is focused on better understanding the safety and efficacy determinants of IgG antibody preparations when used during pregnancy to benefit the mother and her baby. Using pregnant guinea pigs, we demonstrated that biodistribution of administered IgG to the fetus increases with gestation and results in lower maternal and higher fetal antibody concentrations as pregnancy progresses. Data suggests that partition of antibody immunotherapy to the fetal compartment may contribute to a lower maternal exposure (as measured by the AUC) and a shorter mean residence time of the IgG therapeutic at the end of pregnancy compared to nonpregnant age-matched controls, irrespective of the administered dose. Our studies provide insights on the importance of selecting an efficacious dose in pregnancy that takes into account IgG biodistribution to the fetus. The use of appropriate animal models of placental transfer and infectious disease during pregnancy would facilitate pharmacokinetic modeling to derive a starting dose in clinical trials. |
| format | Article |
| id | doaj-art-0bd519f8d7944269afb424be3f99abdb |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0bd519f8d7944269afb424be3f99abdb2025-02-03T06:11:31ZengWileyJournal of Immunology Research2314-88612314-71562017-01-01201710.1155/2017/73731967373196Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody TransportYanqun Xu0Iftekhar Mahmood1Lilin Zhong2Pei Zhang3Evi B. Struble4Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, CBER/FDA, Plasma Derivatives Branch, Silver Spring, MD, USADivision of Clinical Evaluation and Pharmacology/Toxicology, Office of Tissues and Advanced Therapies, CBER/FDA, Silver Spring, MD, USADivision of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, CBER/FDA, Plasma Derivatives Branch, Silver Spring, MD, USADivision of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, CBER/FDA, Plasma Derivatives Branch, Silver Spring, MD, USADivision of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, CBER/FDA, Plasma Derivatives Branch, Silver Spring, MD, USAPregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach for protecting the mother and the neonate from infections remains a high priority. Our work is focused on better understanding the safety and efficacy determinants of IgG antibody preparations when used during pregnancy to benefit the mother and her baby. Using pregnant guinea pigs, we demonstrated that biodistribution of administered IgG to the fetus increases with gestation and results in lower maternal and higher fetal antibody concentrations as pregnancy progresses. Data suggests that partition of antibody immunotherapy to the fetal compartment may contribute to a lower maternal exposure (as measured by the AUC) and a shorter mean residence time of the IgG therapeutic at the end of pregnancy compared to nonpregnant age-matched controls, irrespective of the administered dose. Our studies provide insights on the importance of selecting an efficacious dose in pregnancy that takes into account IgG biodistribution to the fetus. The use of appropriate animal models of placental transfer and infectious disease during pregnancy would facilitate pharmacokinetic modeling to derive a starting dose in clinical trials.http://dx.doi.org/10.1155/2017/7373196 |
| spellingShingle | Yanqun Xu Iftekhar Mahmood Lilin Zhong Pei Zhang Evi B. Struble Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport Journal of Immunology Research |
| title | Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport |
| title_full | Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport |
| title_fullStr | Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport |
| title_full_unstemmed | Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport |
| title_short | Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport |
| title_sort | passive immunoprophylaxis for the protection of the mother and her baby insights from in vivo models of antibody transport |
| url | http://dx.doi.org/10.1155/2017/7373196 |
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