Biology subjects

Beukema, M.

Publications and source records attributed to Beukema, M..

3 recordsLinked to original sources

bioRxiv2026

Polymorphonuclear neutrophils modulate the responses of human immune cells to vaccines in an in vitro blood cell culture system

Vaccine-induced immune responses are the result of an intricate interplay between different cell populations of the innate and adaptive immune system, which is so far only partly understood. In particular, the role of polymorphonuclear neutrophils (PMNs) has long been neglected. Here, we studied the effects of a whole inactivated virus influenza vaccine (WIV) in an in vitro system consisting of freshly isolated human PMNs alone or PMNs combined with autologous peripheral blood mononuclear cells (PBMCs). Isolated PMNs showed minimal responses to the vaccine with respect to apoptosis, gene expression, cytokine production, and reactive oxygen species production. However, in WIV-stimulated PMN/PBMC co-cultures, PMNs particularly enhanced monocyte dynamics, CD14-CD11c+ cell activation, effector T cell differentiation, and B cell antibody production. On the other hand, PMNs decreased T follicular helper cell frequencies. Without vaccine stimulation, PMN presence resulted in enhanced levels of baseline inflammatory cytokines in PMN/PBMC co-cultures. However, with vaccine stimulation, PMNs dampened the vaccine-induced cytokine secretion of PBMCs. These findings reveal PMNs as regulators of vaccine responses whose effects depend on crosstalk with other immune cells, balancing pro-inflammatory and adaptive immune activation. Author summaryPolymorphonuclear neutrophils (PMNs) are essential and predominant cells of the human innate immune system. Growing evidence implicates that PMNs are involved in vaccine-induced immune activation, but their exact role is so far poorly defined. In our study, human PMNs were tested alone to observe their response to whole inactivated virus influenza vaccine (WIV), or combined with autologous peripheral blood mononuclear cells (PBMCs) to investigate how their presence influences vaccine responses of various cell populations within PBMCs. Our results show that WIV had little direct effect on isolated PMNs. However, when PMNs were combined with other immune cells, PMNs acted as crucial regulators: they enhanced the activity of innate immune cells, regulated the responses to the vaccine of T and B cells, and helped control the overall level of inflammation. Our study forms the groundwork for a more comprehensive understanding of human immune cell interactions under vaccine stimulation.

immunology↗

bioRxiv2026

Immune-competent apical out airway organoids reveal distinct antiviral strategies of macrophages, neutrophils, and monocytes during influenza infection

The respiratory mucosa is the primary entry site for influenza virus and early antiviral immunity is governed there by interactions between epithelial cells and innate immune cells. However, mechanistic insight into these interactions in a human context is limited. Here, we established an immune-competent apical-out human airway organoid model that enables direct epithelial infection and controlled integration of innate immune cells. The organoids recapitulate key features of the human upper airway epithelium and support productive influenza virus replication. Using defined co-cultures, we uncovered distinct innate immune functions: macrophages suppress viral replication and restrict epithelial spread via production of type I and III interferons; neutrophils reduce extracellular virus levels without limiting epithelial infection, consistent with antiviral clearance mechanisms independent of interferon signaling; and monocytes exert modest, transient antiviral effects. Together, we use a human-relevant platform to define how distinct innate immune cells shape mucosal immunity at the respiratory epithelium, with direct implications for antiviral and vaccine development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/729766v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@612404org.highwire.dtl.DTLVardef@183aff0org.highwire.dtl.DTLVardef@93df5forg.highwire.dtl.DTLVardef@2de4a1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2023

Prolonging the Delivery of Influenza Virus Vaccine Improves the Quantity and Quality of the Induced Immune Responses in Mice

Influenza vaccines play a vital role in protecting individuals from influenza virus infection and severe illness. However, current influenza vaccines have suboptimal efficacy, which is further reduced in cases where the vaccine strains do not match the circulating strains. One strategy to enhance the efficacy of influenza vaccines is by extended antigen delivery, thereby mimicking the antigen kinetics of a natural infection. Prolonging antigen availability was shown to quantitatively enhance influenza virus-specific immune responses but how it affects the quality of the induced immune response is unknown. Therefore, the current study aimed to investigate whether prolongation of the delivery of influenza vaccine improves the quality of the induced immune responses over that induced by prime-boost immunization. To study this, mice were given daily doses of whole inactivated influenza virus vaccine for periods of 14, 21, or 28 days; the control group received prime-boost immunization with a 28 days interval. Our data show that the highest levels of cellular and humoral immune responses were induced by 28 days of extended antigen delivery, followed by 21, and 14 days of delivery, and prime-boost immunization. Moreover, prolonging vaccine delivery also improved the quality of the induced antibody response, as indicated by higher level of high avidity antibodies, a balanced IgG subclass profile, and a higher level of cross-reactive antibodies. Overall, our findings contribute to a better understanding of the immune response to influenza vaccination and have important implications for the design and development of future slow-release influenza vaccines.

immunology↗