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1.
J Clin Invest ; 131(13)2021 07 01.
Article in English | MEDLINE | ID: covidwho-1556620

ABSTRACT

Seasonal influenza vaccination elicits a diminished adaptive immune response in the elderly, and the mechanisms of immunosenescence are not fully understood. Using Ig-Seq, we found a marked increase with age in the prevalence of cross-reactive (CR) serum antibodies that recognize both the H1N1 (vaccine-H1) and H3N2 (vaccine-H3) components of an egg-produced split influenza vaccine. CR antibodies accounted for 73% ± 18% of the serum vaccine responses in a cohort of elderly donors, 65% ± 15% in late middle-aged donors, and only 13% ± 5% in persons under 35 years of age. The antibody response to non-HA antigens was boosted by vaccination. Recombinant expression of 19 vaccine-H1+H3 CR serum monoclonal antibodies (s-mAbs) revealed that they predominantly bound to non-HA influenza proteins. A sizable fraction of vaccine-H1+H3 CR s-mAbs recognized with high affinity the sulfated glycans, in particular sulfated type 2 N-acetyllactosamine (Galß1-4GalNAcß), which is found on egg-produced proteins and thus unlikely to contribute to protection against influenza infection in humans. Antibodies against sulfated glycans in egg-produced vaccine had been identified in animals but were not previously characterized in humans. Collectively, our results provide a quantitative basis for how repeated exposure to split influenza vaccine correlates with unintended focusing of serum antibody responses to non-HA antigens that may result in suboptimal immunity against influenza.


Subject(s)
Antibodies, Viral/biosynthesis , Influenza Vaccines/immunology , Influenza, Human/immunology , Viral Proteins/immunology , Adult , Age Factors , Aged , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/blood , Cohort Studies , Cross Reactions , Eggs/analysis , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Middle Aged , Polysaccharides/immunology , Vaccination
2.
Nutrients ; 13(12)2021 Dec 02.
Article in English | MEDLINE | ID: covidwho-1551616

ABSTRACT

A single-center, randomized, double-blind, placebo-controlled study was conducted in 72 volunteers who received a synergistic combination of yeast-based ingredients with a unique ß-1,3/1,6-glucan complex and a consortium of heat-treated probiotic Saccharomyces cerevisiae rich in selenium and zinc (ABB C1®) or placebo on the next day after getting vaccinated against influenza (Chiromas®) (n = 34) or the COVID-19 (Comirnaty®) (n = 38). The duration of treatment was 30 and 35 days for the influenza and COVID-19 vaccine groups, respectively. Mean levels of CD4+T cells increased from 910.7 at baseline to 1000.2 cells/µL after the second dose of the COVID-19 vaccine in the ABB C1® group, whereas there was a decrease from 1055.1 to 929.8 cells/µL in the placebo group. Changes of CD3+T and CD8+T lymphocytes showed a similar trend. In the COVID-19 cohort, the increases in both IgG and IgM were higher in the ABB C1® supplement than in the placebo group. Serum levels of selenium and zinc showed a higher increase in subjects treated with the active product than in those receiving placebo. No serious adverse events related to ABB C1® or tolerance issues were reported. The study findings validate the capacity of the ABB C1® product to stimulate trained immunity.


Subject(s)
COVID-19 Vaccines/administration & dosage , Dietary Supplements , Influenza Vaccines/administration & dosage , Saccharomyces cerevisiae , Selenium/administration & dosage , Zinc/administration & dosage , beta-Glucans/administration & dosage , Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Double-Blind Method , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Influenza Vaccines/immunology , Male , Middle Aged , Selenium/immunology , Zinc/immunology , beta-Glucans/immunology
3.
Sci Rep ; 11(1): 22164, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1514425

ABSTRACT

The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.


Subject(s)
Influenza A virus/immunology , Influenza Vaccines/therapeutic use , Interferon Type I/immunology , Orthomyxoviridae Infections/prevention & control , Vaccines, Attenuated/therapeutic use , Viral Nonstructural Proteins/immunology , Adaptive Immunity , Animals , COVID-19/immunology , COVID-19/prevention & control , Chickens , Gene Deletion , Humans , Influenza A virus/genetics , Influenza Vaccines/genetics , Influenza Vaccines/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Mice , Mice, Inbred C57BL , Orthomyxoviridae Infections/immunology , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Viral Nonstructural Proteins/genetics
4.
Influenza Other Respir Viruses ; 14(5): 530-540, 2020 09.
Article in English | MEDLINE | ID: covidwho-1452864

ABSTRACT

BACKGROUND: Influenza is an acute infection affecting all age groups; however, elderly patients are at an increased risk. We aim to describe the clinical characteristics and the circulation of influenza virus types in elderly patients admitted for severe acute respiratory infection (SARI) to a tertiary care hospital in Bucharest, Romania, part of the I-MOVE+ hospital network. METHODS: We conducted an active surveillance study at the National Institute for Infectious Diseases "Prof. Dr Matei Balș," Bucharest, Romania, during three consecutive influenza seasons: 2015/16, 2016/17, and 2017/18. All patients aged 65 and older admitted to our hospital for SARI were tested for influenza by PCR. RESULTS: A total of 349 eligible patients were tested during the study period, and 149 (42.7%) were confirmed with influenza. Most patients, 321 (92.5%) presented at least one underlying condition at the time of hospital admission, the most frequent being cardiovascular disease, 270 (78.3%). The main influenza viral subtype circulating in 2015/16 was A(H1N1)pdm09, followed by A(H3N2) in 2016/17 and B influenza in 2017/18. Case fatality was highest in the 2015/16 season (3.7%), 0% in 2016/17, and 1.0% in 2017/18. Vaccination coverage in elderly patients with SARI from our study population was 22 (6.3%) over the three seasons. CONCLUSIONS: Our study has highlighted a high burden of comorbidities in elderly patients presenting with SARI during winter season in Romania. The influenza vaccine coverage rate needs to be substantially increased in the elderly population, through targeted interventions.


Subject(s)
Influenza, Human/epidemiology , Sentinel Surveillance , Age Factors , Aged , Aged, 80 and over , Female , Hospitalization/statistics & numerical data , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/genetics , Influenza B virus/immunology , Influenza Vaccines/immunology , Male , Romania/epidemiology , Seasons , Tertiary Healthcare
5.
Infect Genet Evol ; 81: 104270, 2020 07.
Article in English | MEDLINE | ID: covidwho-1452334

ABSTRACT

In the endemic settings of India, high CFR (3.6-7.02%) was observed in the consecutive 2009, 2015 and 2017 A/H1N1pdm09 outbreaks, though in eastern India CFR varied between 0 and 5.5% during same period. Recurrent outbreaks of pandemic Influenza A/H1N1pdm09, fragmented nationwide incidence data, lack of national policy for Influenza vaccination in India underscores the necessity for generating regional level data. Thus, during 2017-19, 4106 referred samples from patients hospitalized with severe acute respiratory illness (SARI) in eastern India were tested for A/H1N1pdm09 infection. Among which 16.5% (n = 677/4106) were found A/H1N1pdm09 positive. Individuals <20 years and middle-aged persons (40-60 years) were most susceptible to A/H1N1pdm09 infection. The vaccine strain (A/human/California/07/2009) which was globally used before 2017, clustered in a different lineage away from the representative eastern Indian strains in the phylogenetic dendrogram. The vaccine strain (A/human/Michigan/45/2015) used in India during the study period and the WHO recommended strain (A/human/Brisbane/02/2018) for 2019-20 flu season for the northern hemisphere, clustered with the circulating isolates in the same lineage-6b. Dissimilarities in the amino acids encompassing the antigenic epitopes were seen to be highest with the vaccine strain- A/human/California/07/2009. The significant amino acid variations in the circulating strains with the current WHO recommended vaccine strain, implies the exigency of continuous pandemic A/H1N1pdm09 surveillance studies in this epidemiological setting. The absence of any Oseltamivir resistant mutation (H275Y) in the neuraminidase gene of the current isolates suggests continuing use of Tamiflu® as an antiviral therapy in suspected subjects in this region.


Subject(s)
Antigenic Variation/genetics , Antigenic Variation/immunology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Adolescent , Adult , Amino Acid Substitution/genetics , Amino Acid Substitution/immunology , Child , Child, Preschool , Drug Resistance, Viral/genetics , Female , Humans , India , Influenza, Human/virology , Male , Middle Aged , Neuraminidase/genetics , Oseltamivir/therapeutic use , Phylogeny , Viral Proteins/genetics , Young Adult
6.
J Virol ; 95(15): e0053021, 2021 07 12.
Article in English | MEDLINE | ID: covidwho-1486507

ABSTRACT

Elicitation of lung tissue-resident memory CD8 T cells (TRMs) is a goal of T cell-based vaccines against respiratory viral pathogens, such as influenza A virus (IAV). C-C chemokine receptor type 2 (CCR2)-dependent monocyte trafficking plays an essential role in the establishment of CD8 TRMs in lungs of IAV-infected mice. Here, we used a combination adjuvant-based subunit vaccine strategy that evokes multifaceted (TC1/TC17/TH1/TH17) IAV nucleoprotein-specific lung TRMs to determine whether CCR2 and monocyte infiltration are essential for vaccine-induced TRM development and protective immunity to IAV in lungs. Following intranasal vaccination, neutrophils, monocytes, conventional dendritic cells (DCs), and monocyte-derived dendritic cells internalized and processed vaccine antigen in lungs. We found that basic leucine zipper ATF-like transcription factor 3 (BATF3)-dependent DCs were essential for eliciting T cell responses, but CCR2 deficiency enhanced the differentiation of CD127hi, KLRG-1lo, OX40+ve CD62L+ve, and mucosally imprinted CD69+ve CD103+ve effector and memory CD8 T cells in lungs and airways of vaccinated mice. Mechanistically, increased development of lung TRMs induced by CCR2 deficiency was linked to dampened expression of T-bet but not altered TCF-1 levels or T cell receptor signaling in CD8 T cells. T1/T17 functional programming, parenchymal localization of CD8/CD4 effector and memory T cells, recall T cell responses, and protective immunity to a lethal IAV infection were unaffected in CCR2-deficient mice. Taken together, we identified a negative regulatory role for CCR2 and monocyte trafficking in mucosal imprinting and differentiation of vaccine-induced TRMs. Mechanistic insights from this study may aid the development of T-cell-based vaccines against respiratory viral pathogens, including IAV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IMPORTANCE While antibody-based immunity to influenza A virus (IAV) is type and subtype specific, lung- and airway-resident memory T cells that recognize conserved epitopes in the internal viral proteins are known to provide heterosubtypic immunity. Hence, broadly protective IAV vaccines need to elicit robust T cell memory in the respiratory tract. We have developed a combination adjuvant-based IAV nucleoprotein vaccine that elicits strong CD4 and CD8 T cell memory in lungs and protects against H1N1 and H5N1 strains of IAV. In this study, we examined the mechanisms that control vaccine-induced protective memory T cells in the respiratory tract. We found that trafficking of monocytes into lungs might limit the development of antiviral lung-resident memory T cells following intranasal vaccination. These findings suggest that strategies that limit monocyte infiltration can potentiate vaccine-induced frontline T-cell immunity to respiratory viruses, such as IAV and SARS-CoV-2.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Immunity, Mucosal , Immunologic Memory , Influenza A virus/immunology , Influenza Vaccines/immunology , Orthomyxoviridae Infections/immunology , Receptors, CCR2/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Influenza A virus/genetics , Influenza Vaccines/genetics , Influenza Vaccines/pharmacology , Lung/immunology , Mice , Mice, Knockout , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/prevention & control , Receptors, CCR2/genetics
7.
PLoS Pathog ; 17(10): e1009928, 2021 10.
Article in English | MEDLINE | ID: covidwho-1484868

ABSTRACT

Non-specific protective effects of certain vaccines have been reported, and long-term boosting of innate immunity, termed trained immunity, has been proposed as one of the mechanisms mediating these effects. Several epidemiological studies suggested cross-protection between influenza vaccination and COVID-19. In a large academic Dutch hospital, we found that SARS-CoV-2 infection was less common among employees who had received a previous influenza vaccination: relative risk reductions of 37% and 49% were observed following influenza vaccination during the first and second COVID-19 waves, respectively. The quadrivalent inactivated influenza vaccine induced a trained immunity program that boosted innate immune responses against various viral stimuli and fine-tuned the anti-SARS-CoV-2 response, which may result in better protection against COVID-19. Influenza vaccination led to transcriptional reprogramming of monocytes and reduced systemic inflammation. These epidemiological and immunological data argue for potential benefits of influenza vaccination against COVID-19, and future randomized trials are warranted to test this possibility.


Subject(s)
COVID-19/immunology , Cross Protection/physiology , Immunity, Innate/physiology , Influenza Vaccines/administration & dosage , COVID-19/epidemiology , COVID-19/prevention & control , Cytokines/immunology , Cytokines/metabolism , Down-Regulation , Imidazoles/immunology , Incidence , Influenza Vaccines/immunology , Netherlands/epidemiology , Personnel, Hospital , Poly I-C/immunology , Proteomics , Risk Factors , Sequence Analysis, RNA
10.
Front Immunol ; 12: 733418, 2021.
Article in English | MEDLINE | ID: covidwho-1450812

ABSTRACT

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Myasthenia Gravis/immunology , Myasthenia Gravis/pathology , SARS-CoV-2/immunology , Autoimmunity/immunology , Humans , Immune Tolerance/immunology , Influenza Vaccines/immunology , Risk , Vaccination/adverse effects
11.
mBio ; 12(4): e0159821, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1360544

ABSTRACT

The gut microbiota plays a critical role in the induction of adaptive immune responses to influenza virus infection. However, the role of nasal bacteria in the induction of the virus-specific adaptive immunity is less clear. Here, we found that disruption of nasal bacteria by intranasal application of antibiotics before influenza virus infection enhanced the virus-specific antibody response in a MyD88-dependent manner. Similarly, disruption of nasal bacteria by lysozyme enhanced antibody responses to intranasally administered influenza virus hemagglutinin (HA) vaccine in a MyD88-dependent manner, suggesting that intranasal application of antibiotics or lysozyme could release bacterial pathogen-associated molecular patterns (PAMPs) from disrupted nasal bacteria that act as mucosal adjuvants by activating the MyD88 signaling pathway. Since commensal bacteria in the nasal mucosal surface were significantly lower than those in the oral cavity, intranasal administration of HA vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to an intranasally administered HA vaccine. Finally, we demonstrated that oral bacteria combined with an intranasal vaccine protect from influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our results reveal the role of nasal bacteria in the induction of the virus-specific adaptive immunity and provide clues for developing better intranasal vaccines. IMPORTANCE Intranasal vaccination induces the nasal IgA antibody which is protective against respiratory viruses, such as influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, understanding how mucosal immune responses are elicited following viral infection is important for developing better vaccines. Here, we focused on the role of nasal commensal bacteria in the induction of immune responses following influenza virus infection. To deplete nasal bacteria, we intranasally administered antibiotics to mice before influenza virus infection and found that antibiotic-induced disruption of nasal bacteria could release bacterial components which stimulate the virus-specific antibody responses. Since commensal bacteria in nasal mucosa were significantly lower than those in the oral cavity, intranasal administration of split virus vaccine alone was insufficient to induce the vaccine-specific antibody response. However, intranasal supplementation of cultured oral bacteria from a healthy human volunteer enhanced antibody responses to the intranasally administered vaccine. Therefore, both integrity and amounts of nasal bacteria may be critical for an effective intranasal vaccine.


Subject(s)
Bacteria/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Influenza Vaccines/immunology , Nasal Mucosa/microbiology , Orthomyxoviridae Infections/prevention & control , Adaptive Immunity/immunology , Adjuvants, Immunologic , Administration, Intranasal , Animals , Antibodies, Viral/immunology , Cell Line , Chlorocebus aethiops , Dogs , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunity, Mucosal/immunology , Influenza A Virus, H1N1 Subtype/immunology , Madin Darby Canine Kidney Cells , Mice , Mice, Inbred BALB C , Myeloid Differentiation Factor 88/metabolism , Nasal Mucosa/immunology , Pathogen-Associated Molecular Pattern Molecules/immunology , SARS-CoV-2/immunology , Vaccination/methods , Vero Cells
12.
Expert Rev Vaccines ; 20(9): 1059-1063, 2021 09.
Article in English | MEDLINE | ID: covidwho-1348017

ABSTRACT

INTRODUCTION: The Development of the SARS-CoV-2 virus vaccine and its update on an ongoing pandemic is the first subject of the world health agenda. AREAS COVERED: First, we will scrutinize the biological features of the measles virus (MV), variola virus (smallpox virus), influenza virus, and their vaccines to compare them with the SARS-CoV-2 virus and vaccine. Next, we will discuss the statistical details of measuring the effectiveness of an improved vaccine. EXPERT OPINION: Amidst the pandemic, we ought to acknowledge our prior experiences with respiratory viruses and vaccines. In the planning stage of observational Phase-III vaccine effectiveness studies, the sample size, sampling method, statistical model, and selection of variables are crucial in obtaining high-quality and valid results.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunity, Cellular/immunology , SARS-CoV-2/immunology , COVID-19/pathology , Humans , Influenza Vaccines/immunology , Mass Vaccination/methods , Measles virus/immunology , Measles-Mumps-Rubella Vaccine/immunology , Orthomyxoviridae/immunology , Smallpox Vaccine/immunology , Vaccination , Vaccines, Attenuated/immunology , Variola virus/immunology
13.
Int Immunopharmacol ; 99: 108020, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330896

ABSTRACT

The spike protein of the SARS-CoV-2 virus is the foremost target for the designing of vaccines and therapeutic antibodies and also acts as a crucial antigen in the assessment of COVID-19 immune responses. The enveloped viruses; such as SARS-CoV-2, Human Immunodeficiency Virus-1 (HIV-1) and influenza, often hijack host-cell glycosylation pathways and influence pathobiology and immune selection. These glycan motifs can lead to either immune evasion or viral neutralization by the production of cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection. Potential cross-protection from influenza vaccine has also been reported in COVID-19 infected individuals in several epidemiological studies recently; however, the scientific basis for these observations remains elusive. Herein, we show that the anti-SARS-CoV2 antibodies cross-reacts with the Hemagglutinin (HA) protein. This phenomenon is common to both the sera from convalescent SARS-CoV-2 donors and spike immunized mice, although these antibodies were unable to cross-neutralize, suggesting the presence of a non-neutralizing antibody response. Epitope mapping suggests that the cross-reactive antibodies are targeted towards glycan epitopes of the SARS-CoV-2 spike and HA. Overall, our findings address the cross-reactive responses, although non-neutralizing, elicited against RNA viruses and warrant further studies to investigate whether such non-neutralizing antibody responses can contribute to effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or ADE.


Subject(s)
COVID-19/immunology , Cross Reactions/immunology , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing , Antigen-Antibody Reactions , Binding Sites, Antibody/immunology , Cell Culture Techniques , Chlorocebus aethiops , Dogs , Epitope Mapping , Epitopes/immunology , Glycosylation , Humans , Influenza Vaccines/immunology , Madin Darby Canine Kidney Cells , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , SARS-CoV-2/immunology , Vero Cells
15.
Genes (Basel) ; 12(7)2021 06 25.
Article in English | MEDLINE | ID: covidwho-1295802

ABSTRACT

Peripheral blood transcriptome is a highly promising area for biomarker development. However, transcript abundances (TA) in these cell mixture samples are confounded by proportions of the component leukocyte subpopulations. This poses a challenge to clinical applications, as the cell of origin of any change in TA is not known without prior cell separation procedure. We developed a framework to develop a cell-type informative TA biomarkers which enable determination of TA of a single cell-type (B lymphocytes) directly in cell mixture samples of peripheral blood (e.g., peripheral blood mononuclear cells, PBMC) without the need for subpopulation separation. It is applicable to a panel of genes called B cell informative genes. Then a ratio of two B cell informative genes (a target gene and a stably expressed reference gene) obtained in PBMC was used as a new biomarker to represent the target gene expression in purified B lymphocytes. This approach, which eliminates the tedious procedure of cell separation and directly determines TA of a leukocyte subpopulation in peripheral blood samples, is called the Direct LS-TA method. This method is applied to gene expression datasets collected in influenza vaccination trials as early predictive biomarkers of seroconversion. By using TNFRSF17 or TXNDC5 as the target genes and TNFRSF13C or FCRLA as the reference genes, the Direct LS-TA B cell biomarkers were determined directly in the PBMC transcriptome data and were highly correlated with TA of the corresponding target genes in purified B lymphocytes. Vaccination responders had almost a 2-fold higher Direct LS-TA biomarker level of TNFRSF17 (log 2 SMD = 0.84, 95% CI = 0.47-1.21) on day 7 after vaccination. The sensitivity of these Direct LS-TA biomarkers in the prediction of seroconversion was greater than 0.7 and area-under curves (AUC) were over 0.8 in many datasets. In this paper, we report a straightforward approach to directly estimate B lymphocyte gene expression in PBMC, which could be used in a routine clinical setting. Moreover, the method enables the practice of precision medicine in the prediction of vaccination response. More importantly, seroconversion could now be predicted as early as day 7. As the acquired immunology pathway is common to vaccination against influenza and COVID-19, these biomarkers could also be useful to predict seroconversion for the new COVID-19 vaccines.


Subject(s)
B-Lymphocytes/physiology , Gene Expression , Influenza Vaccines/immunology , Seroconversion/genetics , B-Cell Activation Factor Receptor/genetics , Biomarkers/analysis , COVID-19 Vaccines/immunology , Computational Biology/methods , Databases, Genetic , Humans , Leukocytes, Mononuclear/physiology , Models, Theoretical , Network Meta-Analysis , Protein Disulfide-Isomerases/genetics , ROC Curve , Receptors, Fc/genetics , Seroconversion/physiology
16.
J Infect Dis ; 224(1): 49-59, 2021 07 02.
Article in English | MEDLINE | ID: covidwho-1294731

ABSTRACT

BACKGROUND: We investigated frequency of reinfection with seasonal human coronaviruses (HCoVs) and serum antibody response following infection over 8 years in the Household Influenza Vaccine Evaluation (HIVE) cohort. METHODS: Households were followed annually for identification of acute respiratory illness with reverse-transcription polymerase chain reaction-confirmed HCoV infection. Serum collected before and at 2 time points postinfection were tested using a multiplex binding assay to quantify antibody to seasonal, severe acute respiratory syndrome coronavirus (SARS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins and SARS-CoV-2 spike subdomains and N protein. RESULTS: Of 3418 participants, 40% were followed for ≥3 years. A total of 1004 HCoV infections were documented; 303 (30%) were reinfections of any HCoV type. The number of HCoV infections ranged from 1 to 13 per individual. The mean time to reinfection with the same type was estimated at 983 days for 229E, 578 days for HKU1, 615 days for OC43, and 711 days for NL63. Binding antibody levels to seasonal HCoVs were high, with little increase postinfection, and were maintained over time. Homologous, preinfection antibody levels did not significantly correlate with odds of infection, and there was little cross-response to SARS-CoV-2 proteins. CONCLUSIONS: Reinfection with seasonal HCoVs is frequent. Binding anti-spike protein antibodies do not correlate with protection from seasonal HCoV infection.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus , Family Characteristics , Influenza Vaccines/immunology , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Severe Acute Respiratory Syndrome/epidemiology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , Coinfection/epidemiology , Coronavirus/classification , Coronavirus/genetics , Coronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cross Reactions/immunology , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/virology , Kaplan-Meier Estimate , Michigan/epidemiology , Proportional Hazards Models , Public Health Surveillance , Reinfection/epidemiology , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Seasons , Seroepidemiologic Studies , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/virology , Viral Load
17.
Workplace Health Saf ; 69(10): 448-454, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1287256

ABSTRACT

BACKGROUND: In the United States, millions of people contract the flu each year. Immunization has been shown to provide the best protection against the flu. Increasing flu vaccination rates can reduce the number of patients who get the flu and seek care for non-specific symptoms thus making detection of the coronavirus more efficient. METHOD: A quality improvement project was implemented to increase the number of influenza vaccines received by employees at an onsite employer-based health clinic. Anonymous pre- and post-surveys were used to assess the flu knowledge of employees. Employees from a large financial group, who voluntarily participated, received an educational handout at the onsite health fair or at a lunch and learn. Full-time employees who carried their employer's health insurance were eligible to participate, whereas, dependents and contract employees were excluded. FINDINGS: The number of employees who received the vaccination increased during the fall of 2019 (n = 406) when compared with the previous year (n = 337). Nineteen percent (n = 170) of employees completed surveys. There were statistically significantly more post- than pre-survey responses reflecting the participants' perceived knowledge of influenza and the flu vaccine. The majority of participants in both the pre- and post-surveys reported that they learned "a lot" about both influenza and the flu vaccine. CONCLUSION: Providing education and access to the vaccine in the workplace may improve flu knowledge, reduce barriers, and increase flu vaccine uptake among employees.


Subject(s)
Immunization Programs/organization & administration , Influenza, Human/prevention & control , Occupational Health Services/organization & administration , Vaccination/statistics & numerical data , Adult , Aged , Health Knowledge, Attitudes, Practice , Humans , Influenza Vaccines/immunology , Middle Aged , Quality Improvement , Surveys and Questionnaires , Vaccination/economics , Young Adult
18.
Front Immunol ; 12: 626717, 2021.
Article in English | MEDLINE | ID: covidwho-1285285

ABSTRACT

Vaccination during pregnancy is a safe and effective intervention to protect women from potentially severe consequences of influenza and reduce risk of influenza and pertussis in their infants. However, coverage remains variable. In this mini-review we update findings from a 2015 systematic review to describe results from recent studies in high income countries on the uptake of influenza and pertussis vaccination in pregnancy, reasons for vaccine hesitancy and barriers to increasing uptake, from maternal and healthcare provider (HCP) perspectives. Studies reported highly variable uptake (from 0% to 78%). A main facilitator for uptake among pregnant women was receiving a recommendation from their HCP. However, studies showed that HCP awareness of guidelines did not consistently translate into them recommending vaccines to pregnant women. Safety concerns are a well-established barrier to uptake/coverage of maternal immunization; 7%-52% of unvaccinated women gave safety concerns as a reason but these were also present in vaccinated women. Knowledge/awareness gaps among pregnant women and lack of confidence among HCPs to discuss vaccination were both important barriers. Several studies indicated that midwives were more likely to express safety concerns than other HCPs, and less likely to recommend vaccination to pregnant women. Women who perceived the risk of infection to be low were less likely to accept vaccination in several studies, along with women with prior vaccine refusal. Findings highlight the importance of further research to explore context-specific barriers to vaccination in pregnancy, which may include lack of vaccine confidence among pregnant woman and HCPs, and policy and structural factors.


Subject(s)
Influenza Vaccines/immunology , Patient Acceptance of Health Care , Pertussis Vaccine/immunology , Pregnancy Complications, Infectious/prevention & control , Vaccination , COVID-19 Vaccines/immunology , Female , Health Personnel , Humans , Pregnancy , Pregnant Women , Vaccination/adverse effects
19.
Viruses ; 13(6)2021 05 24.
Article in English | MEDLINE | ID: covidwho-1282632

ABSTRACT

Traditional influenza vaccines generate strain-specific antibodies which cannot provide protection against divergent influenza virus strains. Further, due to frequent antigenic shifts and drift of influenza viruses, annual reformulation and revaccination are required in order to match circulating strains. Thus, the development of a universal influenza vaccine (UIV) is critical for long-term protection against all seasonal influenza virus strains, as well as to provide protection against a potential pandemic virus. One of the most important strategies in the development of UIVs is the selection of optimal targeting antigens to generate broadly cross-reactive neutralizing antibodies or cross-reactive T cell responses against divergent influenza virus strains. However, each type of target antigen for UIVs has advantages and limitations for the generation of sufficient immune responses against divergent influenza viruses. Herein, we review current strategies and perspectives regarding the use of antigens, including hemagglutinin, neuraminidase, matrix proteins, and internal proteins, for universal influenza vaccine development.


Subject(s)
Antigens, Viral/immunology , Host-Pathogen Interactions/immunology , Influenza A virus/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Adjuvants, Immunologic , Animals , Antigens, Viral/chemistry , Cross Protection/immunology , Hemagglutinin Glycoproteins, Influenza Virus/chemistry , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Models, Molecular , Structure-Activity Relationship
20.
Viruses ; 13(6)2021 05 24.
Article in English | MEDLINE | ID: covidwho-1273516

ABSTRACT

Despite seasonal influenza vaccines having been routinely used for many decades, influenza A virus continues to pose a global threat to humans, causing high morbidity and mortality each year. The effectiveness of the vaccine is largely dependent on how well matched the vaccine strains are with the circulating influenza virus strains. Furthermore, low vaccine efficacy in naïve populations such as young children, or in the elderly, who possess weakened immune systems, indicates that influenza vaccines need to be more personalized to provide broader community protection. Advances in both vaccine technologies and our understanding of influenza virus infection and immunity have led to the design of a variety of alternate vaccine strategies to extend population protection against influenza, some of which are now in use. In this review, we summarize the progress in the field of influenza vaccines, including the advantages and disadvantages of different strategies, and discuss future prospects. We also highlight some of the challenges to be faced in the ongoing effort to control influenza through vaccination.


Subject(s)
Influenza A virus/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Precision Medicine , Adjuvants, Immunologic , Clinical Decision-Making , Disease Management , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Influenza Vaccines/classification , Influenza, Human/epidemiology , Precision Medicine/methods , Public Health Surveillance , Research , Vaccination
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