Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy

Wilcox, Christopher R; Holder, Beth; Jones, Christine E

doi:10.3389/fimmu.2017.01294

Cited by 135 publications

(150 citation statements)

References 148 publications

(164 reference statements)

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“…1 The concentration of fetal IgG in late second and early third trimester is 25%-50% lower than that found in term infants, which has significant relevance for the timing of vaccination in pregnancy to provide protection to preterm infants. There remains debate in the literature about the optimal timing of vaccination in pregnancy.…”

Section: Mechanisms Of Protection By Vaccination In Pregnancymentioning

confidence: 97%

Vaccination in Pregnancy—Recent Developments

Jones¹,

Calvert

Doare³

2018

Pediatric Infectious Disease Journal

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Section: Mechanisms Of Protection By Vaccination In Pregnancymentioning

confidence: 97%

Vaccination in Pregnancy—Recent Developments

Jones¹,

Calvert

Doare³

2018

Pediatric Infectious Disease Journal

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“…28 While low molecular weight compounds (<500 Da) can simply diffuse across this placental barrier, larger compounds are generally prevented from traversing an intact placenta in the absence of an active transport mechanism. 46 At least some malaria antigens appear to be transported across the placenta as immune complexes, 19,39 which are ferried across the syncytiotrophoblast cell layer by FcRn, the neonatal Fc receptor. FcRn is expressed by syncytiotrophoblast cells and acts as a pH-dependent shuttle.…”

Section: Mal Aria Anti G En E Xp Osure I N Uteromentioning

confidence: 99%

The immune response to malaria in utero

Feeney

2019

Immunological Reviews

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Malaria caused by Plasmodium falciparum is a leading killer of infants and children. Efforts to develop a protective vaccine have been hindered by the parasite's numerous evasion strategies, which include the induction of immunoregulatory mechanisms in the human host.Indeed, several promising vaccine candidates that induce robust protection in malaria-naive populations have been shown to have much lower efficacy when administered to individuals residing in endemic settings, 1,2 suggesting that immunomodulatory mechanisms induced by prior malaria exposure may pose a critical barrier to vaccine-mediated protection. In endemic regions, many individuals are first exposed to malaria in utero, when P. falciparum-infected red blood cells sequester in the placenta and parasite antigens cross the syncytiotrophoblast barrier, gaining entry into the fetal circulation.Therefore, even during the neonatal period, vaccination may be influenced by prior malaria exposure. Here, we examine the consequences of in utero antigen exposure for fetal immune development and postnatal immunity. The worldwide burden posed by malaria-related complications of pregnancy is profound. More than 125 million pregnancies occur annually in regions at risk for malaria transmission, 3 and one in four pregnant women in sub-Saharan Africa have evidence of infection with malaria at parturition. 4 Although most placental malaria (PM) infections are attributable to P. falciparum, recent evidence indicates that P.vivax is also associated with poor pregnancy outcomes, and some data suggest that it too may sequester in the placenta. 5,6 Pregnancy-associated malaria results in tremendous obstetrical and pediatric morbidity, AbstractMalaria causes tremendous early childhood morbidity and mortality, providing an urgent impetus for the development of a vaccine that is effective in neonates. However, the infant immune response to malaria may be influenced by events that occur well before birth. Placental malaria infection complicates one quarter of all pregnancies in Africa and frequently results in exposure of the fetus to malaria antigens in utero, while the immune system is still developing. Some data suggest that in utero exposure to malaria may induce immunologic tolerance that interferes with the development of protective immunity during childhood. More recently, however, a growing body of evidence suggests that fetal malaria exposure can prime highly functional malariaspecific T-and B-cells, which may contribute to postnatal protection from malaria. In utero exposure to malaria also impacts the activation and maturation of fetal antigen presenting cells and innate lymphocytes, which could have implications for global immunity in the infant. Here, we review recent advances in our understanding of how various components of the fetal immune system are altered by in utero exposure to malaria, discuss factors that may tilt the critical balance between tolerance and adaptive immunity, and consider the implications of these findings for malaria prevention strateg...

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“…Another study limitation is that antibody isotypes other than IgG (such as IgM or IgE) were not measured. We focused on IgGs because, among the five isotypes of human antibodies, only IgG is transferred in significant quantities across the placenta, 38 where it could potentially affect fetal neogenin function. Altogether, given the presented immunogenicity data and the implemented modified vaccine purification processes, the potential risks associated with the presence of the neogenin HCP were considered negligible.…”

Section: Discussionmentioning

confidence: 99%

Hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants

Steff

Cadieux-Dion²,

Lannoy

et al. 2020

Human Vaccines & Immunotherapeutics

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A recombinant respiratory syncytial virus (RSV) fusion glycoprotein candidate vaccine (RSV-PreF) manufactured in Chinese hamster ovary cells was developed for immunization of pregnant women, to protect newborns against RSV disease through trans-placental antibody transfer. Traces of a host-cell protein, hamster neogenin (haNEO1), were identified in purified RSV-PreF antigen material. Given the high amino-acid sequence homology between haNEO1 and human neogenin (huNEO1), there was a risk that potential vaccine-induced anti-neogenin immunity could affect huNEO1 function in mother or fetus. Anti-huNEO1 IgGs were measured by enzyme-linked immunosorbent assay in sera from rabbits and trial participants (Phase 1 and 2 trials enrolling 128 men and 500 non-pregnant women, respectively; NCT01905215/NCT02360475) collected after immunization with RSV-PreF formulations containing different antigen doses with/without aluminum-hydroxide adjuvant. In rabbits, four injections administered at 14-day intervals induced huNEO1-specific IgG responses in an antigen-dose-and adjuvantdependent manner, which plateaued in the highest-dose groups after three injections. In humans, no vaccination-induced anti-huNEO1 IgG responses were detected upon a single immunization, as the values in vaccine and control groups fluctuated around pre-vaccination levels up to 90/360 days postvaccination. A minority of participants had anti-huNEO1 levels ≥ assay cutoff before vaccination, which did not increase post-vaccination. Thus, despite detecting vaccine-induced huNEO1-specific responses in rabbits, we found no evidence that the candidate vaccine had induced anti-huNEO1 immunity in human adults. The antigen purification process was nevertheless optimized, and haNEO1-reduced vaccines were used in a subsequent Phase 2 trial enrolling 400 non-pregnant women (NCT02956837), in which again no vaccine-induced anti-huNEO1 responses were detected. ARTICLE HISTORY

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Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy

Cited by 135 publications

References 148 publications

Vaccination in Pregnancy—Recent Developments

Vaccination in Pregnancy—Recent Developments

The immune response to malaria in utero

Hamster neogenin, a host-cell protein contained in a respiratory syncytial virus candidate vaccine, induces antibody responses in rabbits but not in clinical trial participants

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