High-throughput spatiotemporal monitoring of single-cell secretions via plasmonic microwell arrays.

Methods for the analysis of cell secretions at the single-cell level only provide semiquantitative endpoint readouts. Here we describe a microwell array for the real-time spatiotemporal monitoring of extracellular secretions from hundreds of single cells in parallel. The microwell array incorporates a gold substrate with arrays of nanometric holes functionalized with receptors for a specific analyte, and is illuminated with light spectrally overlapping with the device's spectrum of extraordinary optical transmission. Spectral shifts in surface plasmon resonance resulting from analyte-receptor bindings around a secreting cell are recorded by a camera as variations in the intensity of the transmitted light while machine-learning-assisted cell tracking eliminates the influence of cell movements. We used the microwell array to characterize the antibody-secretion profiles of hybridoma cells and of a rare subset of antibody-secreting cells sorted from human donor peripheral blood mononuclear cells. High-throughput measurements of spatiotemporal secretory profiles at the single-cell level will aid the study of the physiological mechanisms governing protein secretion.

Influence of Timing of Maternal Pertussis Immunization on the Avidity of Transferred Antibodies in Term and Preterm Neonates.

The timing of maternal pertussis vaccination influences the titers of cord-blood anti-pertussis antibodies. Whether it affects their avidity is unknown. We demonstrate in 298 term and 72 preterm neonates that antibody avidity is independent of the timing of maternal vaccination, whether comparing second with third trimester or intervals before birth.

Adjuvanted recombinant zoster vaccine in solid organ transplant and hematopoietic stem-cell transplant recipients.

PURPOSE OF REVIEW: Hematopoietic stem-cell (HSCT) and solid organ transplant (SOT) recipients are particularly at risk to develop herpes zoster and its complications. A recently approved nonlive, adjuvanted recombinant zoster vaccine (aRZV) is a potential candidate to provide durable prevention of herpes zoster. This review summarizes current scientific evidence and expert recommendations for its use in these populations and offers practical clinical guidance. RECENT FINDINGS: Recent clinical trials have shown aRZV to be well tolerated and efficacious in the prevention of herpes zoster, even in the elderly. Data are emerging that this vaccine might also be effective in immunocompromised individuals, such as SOT and HSCT recipients. Evidence is sparse regarding optimal timing of vaccination and durability of responses. However, several specialized societies have already established expert-based aRZV immunization recommendations for these vulnerable populations. SUMMARY: Practical considerations, safety concerns, and timing of vaccine administration vary from one immunocompromised subpopulation to another. Initial studies show that aRZV has a favorable safety and immunogenicity profile in SOT and HSCT recipients. However, data are sparse, particularly in allogeneic HSCT, and practical recommendations are mostly based on expert opinion. Additional research is needed to offer better insight on aRZV administration in immunocompromised patients.

Is there a role for childhood vaccination against COVID-19?

Tremendous efforts are undertaken to quickly develop COVID-19 vaccines that protect vulnerable individuals from severe disease and thereby limit the health and socioeconomic impacts of the pandemic. Potential candidates are tested in adult populations, and questions arise of whether COVID-19 vaccination should be implemented in children. Compared to adults, the incidence and disease severity of COVID-19 are low in children, and despite their infectiveness, their role in disease propagation is limited. Therefore, COVID-19 vaccines will need to have fully demonstrated safety and efficacy in preventing not only complications but transmission to justify childhood vaccination. This work summarizes currently tested vaccine platforms and debates practical and ethical considerations for their potential use in children. It also discusses the already deleterious effect of the pandemic on routine childhood vaccine coverage, calling for action to limit the risks for a rise in vaccine-preventable diseases.

Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers.

Maternal antibodies (MatAbs) protect offspring from infections but limit their responses to vaccination. The mechanisms of this inhibition are still debated. Using murine early-life immunization models mimicking the condition prevailing in humans, we observed the induction of CD4-T, T follicular helper, and germinal center (GC) B cell responses even when early-life antibody responses were abrogated by MatAbs. GC B cells induced in the presence of MatAbs form GC structures and exhibit canonical GC changes in gene expression but fail to differentiate into plasma cells and/or memory B cells in a MatAb titer-dependent manner. Furthermore, GC B cells elicited in the presence or absence of MatAbs use different VH and Vk genes and show differences in genes associated with B cell differentiation and isotype switching. Thus, MatAbs do not prevent B cell activation but control the output of the GC reaction both quantitatively and qualitatively, shaping the antigen-specific B cell repertoire.

Antenatal vaccination to decrease pertussis in infants: safety, effectiveness, timing, and implementation.

Pertussis remains a serious global health issue in infants aged less than 6 months. Neonates and young infants have the highest risk of developing pertussis as they are too young to be vaccinated and thus are more likely to develop more severe pertussis-related complications, including death. Protecting this vulnerable age population from pertussis is considered a main priority in many national health programs. Two vaccine strategies exist to protect infants from pertussis: "cocooning" and maternal vaccination during pregnancy. The latter is the more recent and preferred strategy, which protects newborns by passive transplacental transfer of pertussis antibodies. We review the reported evidence on the safety, effectiveness, timing and implementation of this antenatal immunization strategy.

Overcoming the Neonatal Limitations of Inducing Germinal Centers through Liposome-Based Adjuvants Including C-Type Lectin Agonists Trehalose Dibehenate or Curdlan.

Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system. Here, we assessed the neonatal adjuvanticity of three novel adjuvants including TLR4 (glucopyranosyl lipid adjuvant-squalene emulsion), TLR9 (IC31®), and Mincle (CAF01) agonists, which all induce germinal centers (GCs) and potent antibody responses to influenza hemagglutinin (HA) in adult mice. In neonates, a single dose of HA formulated into each adjuvant induced T follicular helper (TFH) cells. However, only HA/CAF01 elicited significantly higher and sustained antibody responses, engaging neonatal B cells to differentiate into GCs already after a single dose. Although antibody titers remained lower than in adults, HA-specific responses induced by a single neonatal dose of HA/CAF01 were sufficient to confer protection against influenza viral challenge. Postulating that the neonatal adjuvanticity of CAF01 may result from the functionality of the C-type lectin receptor (CLR) Mincle in early life we asked whether other C-type lectin agonists would show a similar neonatal adjuvanticity. Replacing the Mincle agonist trehalose 6,6'-dibehenate by Curdlan, which binds to Dectin-1, enhanced antibody responses through the induction of similar levels of TFH, GCs and bone marrow high-affinity plasma cells. Thus, specific requirements of early life B cells may already be met after a single vaccine dose using CLR-activating agonists, identified here as promising B cell immunostimulators for early life vaccines when included into cationic liposomes.

[Recommendations for the vaccination of pregnant women : a booster injection]. / Recommandations de vaccination chez la femme enceinte : une piqûre de rappel.

For several decades we have avoided the immunisation of pregnant women, with the only exception being that of the tetanus vaccination in the absence of a previous basic immunisation. Nowadays, it is strongly advised to give several vaccines specifically during pregnancy : maternal immunisations against pertussis and influenza have been shown to prevent complications in both the foetus and the newborn as well as the woman during pregnancy and after delivery. This article aims to review these recommendations, their rationale and to address potential concerns that are often raised by physicians and patients. Finally, some practical aspects of vaccine administration are detailed.

Alors que pendant longtemps on évitait de vacciner une femme enceinte, hormis contre le tétanos en l'absence de primovaccination, certaines vaccinations sont maintenant recommandées justement pendant la grossesse. C'est le cas pour la coqueluche et la grippe, avec comme objectif d'éviter des complications tant chez le fœtus et la future mère pendant la grossesse que chez le nouveau-né et la mère après la naissance. Cet article a pour but de rappeler ces recommandations, leur justification, ainsi que de répondre à certaines préoccupations souvent relevées par les médecins et leurs patientes. Enfin, certains aspects pratiques de la vaccination sont détaillés.

Needle-free and adjuvant-free epicutaneous boosting of pertussis immunity: Preclinical proof of concept.

The limited durability of pertussis vaccine-induced protection requires novel approaches to reactivate immunity and limit pertussis resurgence in older children and adults. We propose that periodic boosters could be delivered using a novel epicutaneous delivery system (Viaskin) to deliver optimized pertussis antigens such as genetically-detoxified pertussis toxin (rPT). To best mimic the human situation in which vaccine-induced memory cells persist, whereas antibodies wane, we developed a novel adoptive transfer murine model of pertussis immunity. This allowed demonstrating that a single application of Viaskin delivering rPT and/or pertactin and filamentous hemagglutinin effectively reactivates vaccine-induced pertussis immunity and protects against Bordetella pertussis challenge. Recalling pertussis immunity without needles nor adjuvant may considerably facilitate the acceptance and application of periodic boosters.