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      Current Challenges and Achievements in Maternal Immunization Research

      review-article
      1 , 2 , *
      Frontiers in Immunology
      Frontiers Media S.A.
      maternal immunization, ethics, research, pregnancy, inclusion, regulatory, vaccination

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          Abstract

          Maternal immunization has the potential to significantly improve maternal and child health worldwide by reducing maternal and infant morbidity and mortality associated with disease caused by pathogens that are particularly relevant in the perinatal period and in early life, and for which no alternative effective preventive strategies exist. Research on all aspects related to vaccines for administration during pregnancy is ongoing with support of multiple stakeholders and global participation. Substantial progress has been made, and the availability of new vaccines licensed exclusively for use in pregnant women to protect their infants has become an achievable goal. This review provides an update of the current challenges and achievements in maternal immunization research, focusing on recent milestones that advance the field and the prospects to make maternal immunization a feasible and accessible strategy to improve global health.

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          Most cited references29

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          Sustained Effectiveness of the Maternal Pertussis Immunization Program in England 3 Years Following Introduction

          The effectiveness of maternal immunization in preventing infant pertussis was first demonstrated in England, 1 year after the program using diphtheria–tetanus–5-component acellular pertussis–inactivated polio vaccine (dT5aP-IPV) was introduced in 2012. Vaccine effectiveness against laboratory-confirmed pertussis has been sustained >90% in the 3 years following its introduction, despite changing to another acellular vaccine with different antigen composition. Consistent with this, disease incidence in infants <3 months of age has remained low despite high activity persisting in those aged 1 year and older. Vaccine effectiveness against infant deaths was estimated at 95% (95% confidence interval, 79%–100%). Additional protection from maternal immunization is retained in infants who received their first dose of the primary series. There is no longer evidence of additional protection from maternal vaccination after the third infant dose. Although numbers are small and ongoing assessment is required, there is no evidence of increased risk of disease after primary immunization in infants whose mothers received maternal vaccination.
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            Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregnant Women — Advisory Committee on Immunization Practices (ACIP), 2012

            In October 2011, in an effort to reduce the burden of pertussis in infants, the Advisory Committee on Immunization Practices (ACIP) recommended that unvaccinated pregnant women receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) (1). Vaccination of women with Tdap during pregnancy is expected to provide some protection to infants from pertussis until they are old enough to be vaccinated themselves. Tdap given to pregnant women will stimulate the development of maternal antipertussis antibodies, which will pass through the placenta, likely providing the newborn with protection against pertussis in early life, and will protect the mother from pertussis around the time of delivery, making her less likely to become infected and transmit pertussis to her infant (1). The 2011 Tdap recommendation did not call for vaccinating pregnant women previously vaccinated with Tdap. On October 24, 2012, ACIP voted to recommend use of Tdap during every pregnancy. This report summarizes data considered and conclusions made by ACIP and provides guidance for implementing its recommendations. These updated recommendations on use of Tdap in pregnant women aim to optimize strategies for preventing pertussis morbidity and mortality in infants. ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the Director of the Centers for Disease Control and Prevention (CDC) on use of vaccines and related agents for the control of vaccine-preventable diseases in the civilian population of the United States. Recommendations for routine use of vaccines in children and adolescents are harmonized to the greatest extent possible with recommendations made by the American Academy of Pediatrics, the American Academy of Family Physicians (AAFP), and the American College of Obstetricians and Gynecologists. Recommendations for routine use of vaccines in adults are reviewed and approved by the American College of Physicians, AAFP, the American College of Obstetricians and Gynecologists, and the American College of Nurse-Midwives. ACIP recommendations adopted by the CDC Director become agency guidelines on the date published in the Morbidity and Mortality Weekly Report (MMWR). The United States has experienced substantial increases in reported pertussis cases over the past several years. Provisional case counts for 2012 have surpassed the last peak year, 2010, with 41,880 pertussis cases and 14 deaths in infants aged 10 years since previous Td), then Tdap should be administered. Optimal timing is between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant. Wound management for pregnant women As part of standard wound management to prevent tetanus, a tetanus toxoid–containing vaccine might be recommended for wound management in a pregnant woman if ≥5 years have elapsed since the previous Td booster. If a Td booster is recommended for a pregnant woman, health-care providers should administer Tdap. Pregnant women with unknown or incomplete tetanus vaccination To ensure protection against maternal and neonatal tetanus, pregnant women who never have been vaccinated against tetanus should receive three vaccinations containing tetanus and reduced diphtheria toxoids. The recommended schedule is 0, 4 weeks, and 6 through 12 months. Tdap should replace 1 dose of Td, preferably between 27 and 36 weeks gestation to maximize the maternal antibody response and passive antibody transfer to the infant. Cocooning ACIP recommends that adolescents and adults (e.g., parents, siblings, grandparents, child-care providers, and health-care personnel) who have or anticipate having close contact with an infant aged <12 months should receive a single dose of Tdap to protect against pertussis if they have not received Tdap previously. Guidance will be forthcoming on revaccination of persons who anticipate close contact with an infant, including postpartum women who previously have received Tdap. Research Needs Future research needs will address the effectiveness of Tdap vaccination of pregnant women to prevent infant pertussis morbidity and mortality, the impact of timing of Tdap during pregnancy on infant pertussis, and safety of multiple doses of Tdap in pregnant women. CDC will monitor and assess the safety of Tdap use during pregnancy. Results from these studies and monitoring systems will inform future considerations made by ACIP on use of Tdap in preventing infant pertussis morbidity and mortality.
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              Maternal immunisation: collaborating with mother nature.

              Maternal immunisation has the potential to substantially reduce morbidity and mortality from infectious diseases after birth. The success of tetanus, influenza, and pertussis immunisation during pregnancy has led to consideration of additional maternal immunisation strategies to prevent group B streptococcus and respiratory syncytial virus infections, among others. However, many gaps in knowledge regarding the immunobiology of maternal immunisation prevent the optimal design and application of this successful public health intervention. Therefore, we did an innovative landscape analysis to identify research priorities. Key topics were delineated through review of the published literature, consultation with vaccine developers and regulatory agencies, and a collaborative workshop that gathered experts across several maternal immunisation initiatives-group B streptococcus, respiratory syncytial virus, pertussis, and influenza. Finally, a global online survey prioritised the identified knowledge gaps on the basis of expert opinion about their importance and relevance. Here we present the results of this worldwide landscape analysis and discuss the identified research gaps.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                06 March 2018
                2018
                : 9
                : 436
                Affiliations
                [1] 1Department of Pediatrics, Baylor College of Medicine , Houston, TX, United States
                [2] 2Department of Molecular Virology and Microbiology, Baylor College of Medicine , Houston, TX, United States
                Author notes

                Edited by: Kirsty Le Doare, Imperial College London, United Kingdom

                Reviewed by: Scott D. Gray-Owen, University of Toronto, Canada; Randy A. Albrecht, Icahn School of Medicine at Mount Sinai, United States

                *Correspondence: Flor M. Munoz, florm@ 123456bcm.edu

                Specialty section: This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.00436
                5845678
                29559976
                2cf3bdab-e286-4e19-800c-b781f5c5d1c9
                Copyright © 2018 Munoz.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 November 2017
                : 19 February 2018
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 48, Pages: 7, Words: 5796
                Categories
                Immunology
                Review

                Immunology
                maternal immunization,ethics,research,pregnancy,inclusion,regulatory,vaccination
                Immunology
                maternal immunization, ethics, research, pregnancy, inclusion, regulatory, vaccination

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