Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses.

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains.

Report of a SPEAC webinar 22 september 2023: Sensorineural hearing loss, lassa virus disease and vaccines.

Lassa virus (LASV) belongs to the Arenavirus family. LASV is endemic in several West Africa countries and causes viral hemorrhagic fevers. The Nigeria CDC has reported that an outbreak in 2024 in 28 states has resulted in 7767 suspected cases of Lassa fever, 971 confirmed cases and 166 confirmed deaths up to 11 August.

Acute Respiratory Illness Is Associated with Memory T Cell Differentiation and Other Immune Cell Changes in an Age-Associated Manner.

Respiratory viruses such as influenza are encountered multiple times through infection and/or vaccination and thus have the potential to shape immune cell phenotypes over time. In particular, memory T cell compartments may be affected, as both CD4+ and CD8+ T cell responses likely contribute to viral control. In this study, we assessed immune phenotypes using cytometry by time of flight in the peripheral blood of 22 humans with acute respiratory illness and 22 age-matched noninfected controls.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

KIRCD8 T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19.

In this work, we find that CD8 T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49CD8 regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8 T cells efficiently eliminated pathogenic gliadin-specific CD4 T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIRCD8 T cells, but not CD4 regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis.

An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging.

While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8-96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians.

The critical role of background rates of possible adverse events in the assessment of COVID-19 vaccine safety.

Beginning in December of 2019, a novel coronavirus, SARS-CoV-2, emerged in China and is now a global pandemic with extensive morbidity and mortality. With the emergence of this threat, an unprecedented effort to develop vaccines against this virus began. As vaccines are now being introduced globally, we face the prospect of millions of people being vaccinated with multiple types of vaccines many of which use new vaccine platforms.

Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination.

Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells.

Vaccine-associated enhanced disease: Case definition and guidelines for data collection, analysis, and presentation of immunization safety data.

This is a Brighton Collaboration Case Definition of the term "Vaccine Associated Enhanced Disease" to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation.

Consensus summary report for CEPI/BC March 12-13, 2020 meeting: Assessment of risk of disease enhancement with COVID-19 vaccines.

A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials.

Memory B Cell Activation, Broad Anti-influenza Antibodies, and Bystander Activation Revealed by Single-Cell Transcriptomics.

Antibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profile the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements.

Determinants governing T cell receptor α/β-chain pairing in repertoire formation of identical twins.

The T cell repertoire in each individual includes T cell receptors (TCRs) of enormous sequence diversity through the pairing of diverse TCR α- and β-chains, each generated by somatic recombination of paralogous gene segments. Whether the TCR repertoire contributes to susceptibility to infectious or autoimmune diseases in concert with disease-associated major histocompatibility complex (MHC) polymorphisms is unknown. Due to a lack in high-throughput technologies to sequence TCR α-β pairs, current studies on whether the TCR repertoire is shaped by host genetics have so far relied only on single-chain analysis.

Pregnancy-Induced Alterations in NK Cell Phenotype and Function.

Pregnant women are particularly susceptible to complications of influenza A virus infection, which may result from pregnancy-induced changes in the function of immune cells, including natural killer (NK) cells. To better understand NK cell function during pregnancy, we assessed the ability of the two main subsets of NK cells, CD56, and CD56 NK cells, to respond to influenza-virus infected cells and tumor cells. During pregnancy, CD56 and CD56 NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-γ.

The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system.

Machine learning has the potential to identify novel biological factors underlying successful antibody responses to influenza vaccines. The first attempts have revealed a high level of complexity in establishing influenza immunity, and many different cellular and molecular components are involved. Of note is that the previously identified correlates of protection fail to account for the majority of individual responses across different age groups and influenza seasons.

Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: An open-label randomized phase 1 clinical trial.

Background: Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response.

Methods: Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18-70 years of age.

SIMON, an Automated Machine Learning System, Reveals Immune Signatures of Influenza Vaccine Responses.

Machine learning holds considerable promise for understanding complex biological processes such as vaccine responses. Capturing interindividual variability is essential to increase the statistical power necessary for building more accurate predictive models. However, available approaches have difficulty coping with incomplete datasets which is often the case when combining studies.

Distinct phenotype of CD4 T cells driving celiac disease identified in multiple autoimmune conditions.

Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4 T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4 T cells specific for disease-driving antigens in multiple autoimmune conditions.

A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring.

Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period.

The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease.

Background: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients.

Objectives: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion.

Signatures of selection in the human antibody repertoire: Selective sweeps, competing subclones, and neutral drift.

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the population genetic signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically.

Diminished B-Cell Response After Repeat Influenza Vaccination.

Annual vaccination with influenza vaccines is recommended for protection against influenza in the United States. Past clinical studies and meta-analysis, however, have reported conflicting results on the benefits of annual vaccination. B-cell responses elicited following repeat influenza vaccinations over multiple seasons have not been examined in detail.

Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging.

Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level.

Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains.

Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70-89) and young (aged 20-29) responders.

Accuracy and Discomfort of Different Types of Intranasal Specimen Collection Methods for Molecular Influenza Testing in Emergency Department Patients.

Study Objective: While development is under way of accurate, point-of-care molecular tests for influenza infection, the optimal specimen type for molecular tests remains unclear. Compared with standard nasopharyngeal swab specimens, less invasive nasal swab and midturbinate swab specimens may cause less patient discomfort and be more suitable for routine emergency department (ED) testing, although possibly at the expense of diagnostic accuracy. We compare both the accuracy of a polymerase chain reaction molecular influenza test and discomfort between these 3 intranasal specimen types.