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Immune Ontogeny and Vaccination in Early Life

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Pathogens-host Immune Interface".

Deadline for manuscript submissions: closed (10 February 2021) | Viewed by 49145

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Special Issue Editors

Dr. Nabila Seddiki

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Guest Editor

Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases, UMR1184, IDMIT Department, Université Paris-Saclay, Inserm, CEA, 92265 Fontenay-aux-Roses, France
Interests: T cells; Tregs; Tfh; vaccines; innate and adaptive immunity; infectious diseases; T cell ontogeny

Prof. Dr. Roger Le Grand

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Guest Editor

Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases, UMR1184, IDMIT Department, Université Paris-Saclay, Inserm, CEA, France
Interests: NHP; HIV; infectious diseases; innate and adaptive immunity; vaccinology

Special Issue Information

Dear Colleagues,

The development of the immune system needs a number of changes that occur during the first years of life. The neonatal immune system is exposed to a large number of previously unseen antigens. Newborn children, especially preterm, are susceptible to infections because of the immaturity of their immune system. Although there is clear evidence now that several factors, including microbial exposure, are necessary for shaping immunity, we still need to understand the basis of this and consequently be able to protect our children by developing better treatments and efficacious vaccines tailored to their immune systems. A large number of great studies have explored these avenues. However, the field is still lacking a good animal model to get insights into immune ontogeny in early life and development of immune-mediated diseases later in life. For us, the non-human primate (NHP) model is a very good candidate to study immune development early in life and to monitor human immune systems in the most comprehensive way, encompassing its’ impact on emerging and re-emerging infectious diseases and vaccinology but also its close interaction with microbiota. We are currently establishing a pediatric immunology program (PIP) where the NHP will be essential and central to developing comprehensive studies that will explore immune ontogeny, microbiome, vaccination, transfer of maternal immunology, system immunology, and serology.

The goal of this Research Topic is to gather several known experts in the field of pediatric immunology, infectious diseases, and vaccinology to give an update on their latest research studies that are relevant to early life newborns and immune-mediated diseases later in life, and to develop a method to use the NHP model in the most comprehensive way to address important/remaining questions in the field.

Dr. Nabila Seddiki
Prof. Dr. Roger Le Grand
Guest Editors

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Keywords

vaccines
innate and adaptive immunity
infectious diseases
T cell ontogeny
early-life immunity
immune system development

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 515 KiB

Open AccessEditorial

Special Issue “Immune Ontogeny and Vaccination in Early Life: How the Non-Human Primate Model Can Help Expand the Current Knowledge in Pediatric Immunology and Infectious Diseases Research”

by Nabila Seddiki and Roger Le Grand

Vaccines 2021, 9(9), 1014; https://doi.org/10.3390/vaccines9091014 - 12 Sep 2021

Viewed by 1537

Abstract

The development of the immune system requires a number of changes that occur during the first months of life [...] Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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Research

Jump to: Editorial, Review

10 pages, 260 KiB

Open AccessCommunication

The Potential Role of Nonhuman Primate Models to Better Comprehend Early Life Immunity and Maternal Antibody Transfer

by Julie Sartoretti and Christiane S. Eberhardt

Vaccines 2021, 9(4), 306; https://doi.org/10.3390/vaccines9040306 - 24 Mar 2021

Cited by 6 | Viewed by 2092

Abstract

Early life immunity is a complex field of research and there are still gaps in knowledge regarding the detailed mechanism of maternal antibody transfer, the impact of maternal antibodies on infant vaccine responses and the ontogeny of human early life immunity. A comprehensive understanding is necessary to identify requirements for early life vaccines and to improve early childhood immunization. New immunological methods have facilitated performing research in the youngest, however, some questions can only be addressed in animal models. To date, mostly murine models are used to study neonatal and infant immunity since they are well-described, easy to use and cost effective. Given their limitations especially in the transfer biology of maternal antibodies and the lack of infectivity of numerous human pathogens, this opinion piece discusses the potential and prerequisites of the nonhuman primate model in studying early life immunity and maternal antibody transfer. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

15 pages, 1810 KiB

Open AccessArticle

Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

by Stefania Dispinseri, Mariangela Cavarelli, Monica Tolazzi, Anna Maria Plebani, Marianne Jansson and Gabriella Scarlatti

Vaccines 2021, 9(3), 260; https://doi.org/10.3390/vaccines9030260 - 14 Mar 2021

Cited by 2 | Viewed by 2663

Abstract

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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15 pages, 7976 KiB

Open AccessArticle

Impact of COVID-19 on Immunization Services for Maternal and Infant Vaccines: Results of a Survey Conducted by Imprint—The Immunising Pregnant Women and Infants Network

by Anja Saso, Helen Skirrow and Beate Kampmann

Vaccines 2020, 8(3), 556; https://doi.org/10.3390/vaccines8030556 - 22 Sep 2020

Cited by 63 | Viewed by 13239

Abstract

The COVID-19 pandemic response has caused disruption to healthcare services globally, including to routine immunizations. To understand immunization service interruptions specifically for maternal, neonatal and infant vaccines, we captured the local experiences of members of the Immunising Pregnant Women and Infants Network (IMPRINT) by conducting an online survey over 2-weeks in April 2020. IMPRINT is a global network of clinicians and scientists working in maternal and neonatal vaccinology. The survey included discrete questions to quantify the extent of disruption as well as free-text options to explore the reasons behind reported disruptions. Of the 48 responses received, the majority (75%) were from low-and-middle-income countries (LMICs). Of all respondents, 50% or more reported issues with vaccine delivery within their country. Thematic analysis identified three key themes behind immunization disruption: “access” issues, e.g., logistical barriers, “provider” issues, e.g., staff shortages and user “concern” about attending immunization appointments due to COVID-19 fear. Access and provider issues were more commonly reported by LMIC respondents. Overall, respondents reported uncertainty among parents and healthcare providers regarding routine immunization. We conclude that further quantification of routine vaccination disruption is needed, alongside health service prioritization, logistical support and targeted communication strategies to reinforce routine immunizations during the COVID-19 response. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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Review

Jump to: Editorial, Research

14 pages, 315 KiB

Open AccessReview

Pediatric COVID-19: Immunopathogenesis, Transmission and Prevention

by Geraldine Blanchard-Rohner, Arnaud Didierlaurent, Anne Tilmanne, Pierre Smeesters and Arnaud Marchant

Vaccines 2021, 9(9), 1002; https://doi.org/10.3390/vaccines9091002 - 8 Sep 2021

Cited by 19 | Viewed by 4122

Abstract

Children are unique in the context of the COVID-19 pandemic. Overall, SARS-CoV-2 has a lower medical impact in children as compared to adults. A higher proportion of children than adults remain asymptomatic following SARS-CoV-2 infection and severe disease and death are also less common. This relative resistance contrasts with the high susceptibility of children to other respiratory tract infections. The mechanisms involved remain incompletely understood but could include the rapid development of a robust innate immune response. On the other hand, children develop a unique and severe complication, named multisystem inflammatory syndrome in children, several weeks after the onset of symptoms. Although children play an important role in the transmission of many pathogens, their contribution to the transmission of SARS-CoV-2 appears lower than that of adults. These unique aspects of COVID-19 in children must be considered in the benefit–risk analysis of vaccination. Several COVID-19 vaccines have been authorized for emergency use in adolescents and clinical studies are ongoing in children. As the vaccination of adolescents is rolled out in several countries, we shall learn about the impact of this strategy on the health of children and on transmission within communities. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

41 pages, 1321 KiB

Open AccessReview

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

by Anja Saso, Beate Kampmann and Sophie Roetynck

Vaccines 2021, 9(8), 877; https://doi.org/10.3390/vaccines9080877 - 7 Aug 2021

Cited by 11 | Viewed by 4974

Abstract

Pertussis (‘whooping cough’) is a severe respiratory tract infection that primarily affects young children and unimmunised infants. Despite widespread vaccine coverage, it remains one of the least well-controlled vaccine-preventable diseases, with a recent resurgence even in highly vaccinated populations. Although the exact underlying reasons are still not clear, emerging evidence suggests that a key factor is the replacement of the whole-cell (wP) by the acellular pertussis (aP) vaccine, which is less reactogenic but may induce suboptimal and waning immunity. Differences between vaccines are hypothesised to be cell-mediated, with polarisation of Th1/Th2/Th17 responses determined by the composition of the pertussis vaccine given in infancy. Moreover, aP vaccines elicit strong antibody responses but fail to protect against nasal colonisation and/or transmission, in animal models, thereby potentially leading to inadequate herd immunity. Our review summarises current knowledge on vaccine-induced cellular immune responses, based on mucosal and systemic data collected within experimental animal and human vaccine studies. In addition, we describe key factors that may influence cell-mediated immunity and how antigen-specific responses are measured quantitatively and qualitatively, at both cellular and molecular levels. Finally, we discuss how we can harness this emerging knowledge and novel tools to inform the design and testing of the next generation of improved infant pertussis vaccines. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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25 pages, 4163 KiB

Open AccessReview

Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

by Natalia Nunez, Louis Réot and Elisabeth Menu

Vaccines 2021, 9(6), 584; https://doi.org/10.3390/vaccines9060584 - 1 Jun 2021

Cited by 21 | Viewed by 5921

Abstract

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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19 pages, 1016 KiB

Open AccessReview

COVID-19 and Pregnancy: Vertical Transmission and Inflammation Impact on Newborns

by Mohamed Joma, Claire-Maelle Fovet, Nabila Seddiki, Pierre Gressens and Mireille Laforge

Vaccines 2021, 9(4), 391; https://doi.org/10.3390/vaccines9040391 - 15 Apr 2021

Cited by 25 | Viewed by 6748

Abstract

The COVID-19 pandemic is ongoing and we are still compiling new findings to decipher and understand SARS-CoV-2 infection during pregnancy. No reports encompass any conclusive confirmation of vertical transmission. Nevertheless, cases of fetal distress and multiple organ failure have been reported, as well as rare cases of fetal demise. While clinicians and scientists continue to seek proof of vertical transmission, they miss the greater point, namely the cause of preterm delivery. In this review, we suggest that the cause might not be due to the viral infection but the fetal exposure to maternal inflammation or cytokine storm that translates into a complication of COVID-19. This statement is extrapolated from previous experience with infections and inflammation which were reported to be fatal by increasing the risk of preterm delivery and causing abnormal neonatal brain development and resulting in neurological disorders like atypical behavioral phenotype or autistic syndrome. Given the potentially fatal consequences on neonate health, we highlight the urgent need for an animal model to study vertical transmission. The preclinical model will allow us to make the link between SARS-COV-2 infection, inflammation and long-term follow-up of child brain development. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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13 pages, 298 KiB

Open AccessReview

The Path to New Pediatric Vaccines against Pertussis

by Camille Locht

Vaccines 2021, 9(3), 228; https://doi.org/10.3390/vaccines9030228 - 5 Mar 2021

Cited by 12 | Viewed by 3783

Abstract

Whooping cough, or pertussis, mostly caused by Bordetella pertussis, is a respiratory disease that affects all age groups, but severe and fatal pertussis occurs almost exclusively in young children. The widespread use of whole-cell and, more recently, of acellular vaccines has substantially reduced the disease incidence. However, it has not been eliminated in any part of the world and has made a worrisome rebound in several areas. Cocoon and maternal immunization have been implemented in several countries but have their intrinsic limitations. To effectively control pertussis, novel vaccines are needed that protect against disease and prevent B. pertussis infection and transmission, which is not the case for current vaccines. Several approaches are contemplated, including alternative administration routes, such as nasal immunization, improvement of acellular vaccines by adding more antigens and T-cell-promoting adjuvants, and the development of novel vaccines, such as outer membrane vesicles and live attenuated vaccines. Among them, only a live attenuated vaccine has so far been assessed for safety and immunogenicity in preclinical models other than mice and is in clinical development. Before any of these vaccines can be used in neonates, extensive safety and immunogenicity assessment in pre-clinical neonatal models and in carefully designed clinical trials is necessary. The aim of this review is to discuss the current pertussis problem, implemented strategies to resolve it, the value of animal models and novel vaccine approaches. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

14 pages, 2915 KiB

Open AccessReview

Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

by Daisuke Tokuhara and Norikatsu Hikita

Vaccines 2021, 9(2), 95; https://doi.org/10.3390/vaccines9020095 - 27 Jan 2021

Cited by 7 | Viewed by 3059

Abstract

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood. Full article

(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)

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