Skip to main content

#Cytokine Regulation of #Human #Antibody Responses to #Influenza #Vaccines

Image
By G.M.

 


Abstract

Vaccine responses vary widely in human studies. Here we pooled data measuring 66 cytokines from 4 different inactivated influenza vaccine (IIV) cohorts over 5 seasons (N=581) and identified a significant correlation between baseline/day 0 serum IL-18 and IFN-β concentrations and the antibody response on day 28. We investigated this further in human tonsil and spleen organoids, and found that several cytokines, including multiple Type I IFNs (IFN-β and others), IL-21, IL-12, IL-10, but not IL-18 or its downstream Type II IFN (IFN-β), could adjuvant the IIV vaccine to enhance the antibody response. The live attenuated influenza vaccine (LAIV) induced a stronger antibody response than the inactivated one in organoids. Adding a single cytokine, IFN-β, recapitulated most of the live vaccine-specific cytokine activation program and increased the antibody response of the inactivated vaccine to that of the live vaccine. Thus, the human vaccinees and the organoid data showed that IFN-β is a natural adjuvant. Two other antibody-boosting cytokines, IL-12 and IL-21, were induced by LAIV but not by Type I IFNs, which suggested parallel regulatory pathways. Moreover, IL-21 mRNA lipid nanoparticles (LNPs) greatly augmented the quantity and breadth of antibody responses in a mouse model of IIV vaccination, while IFN-β LNPs enhanced durability. These findings identified parallel cytokine pathways regulating human vaccine responses and provide a rationale for using cytokines as adjuvants to mimic the effectiveness of live-attenuated vaccines- without the risk of side effects.


Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.07.668218v1

____

Labels:

Comments

Post a Comment

Popular posts from this blog

#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

By G.M.
{Excerpt} A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments : M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic , expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries . The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat .1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts , including vertical transmissions , neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential .5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in ext...
Post a Comment
Read more »

No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

By G.M.
Abstract Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion , which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada . Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was...
Post a Comment
Read more »

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

By G.M.
Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...
Post a Comment
Read more »