Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults
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ABSTRACT:
PROVIDER: PRJNA692462 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR13444400_1.fastq.gz | Fastqsanger.gz | |||
| SRR13444400_2.fastq.gz | Fastqsanger.gz | |||
| SRR13444500_1.fastq.gz | Fastqsanger.gz | |||
| SRR13444500_2.fastq.gz | Fastqsanger.gz | |||
| SRR13444401_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. Methods: In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Results: Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. Conclusions: These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.
2021-03-10 | GSE164649 | GEO
Project description:Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to influenza vaccination is not yet fully understood. In this study, we inoculated healthy adults with live Streptococcus pneumoniae and vaccinated them 3 days later with either tetravalent-inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). Vaccine-induced immune responses were assessed in nose, blood, and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, experimentally induced pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared with either the TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. Therefore, nasopharyngeal pneumococcal colonization may affect LAIV efficacy.
| S-EPMC7934923 | biostudies-literature
Project description:Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens1. Live attenuated influenza vaccine (LAIV) is commonly used in children2, but its effectiveness declines with age3. This may be attributed to the gradual accumulation of homo- or hetero-subtypic immunity that blocks vaccine replication necessary to induce protective responses3, 4. Despite its demonstrable efficacy against influenza in children, correlates of protection for LAIV remain elusive5. Studying young adult volunteers we found that LAIV induced distinct, compartmentalized, antibody responses in the mucosa and blood. LAIV also induced mucosal IL-33 release in the first 8 hours post-inoculation and distinct CD8+ and cTfh T cell activation profiles. Mucosal antibodies are induced separately from blood antibodies and may provide a simple and novel correlate of protection for mucosal vaccination.
2023-10-19 | GSE230494 | GEO
Project description:Breastfeeding protects against mucosal infections in infants. The underlying mechanisms through which immunity develops in human milk following maternal infection with mucosal pathogens are not well understood. We simulated nasal mucosal influenza infection through live attenuated influenza vaccination (LAIV) and compared immune responses in milk to inactivated influenza vaccination (IIV). Transcriptomic analysis was performed on RNA extracted from human milk cells to evaluate differentially expressed genes and pathways on days 1 and 7 post-vaccination. Both LAIV and IIV vaccines induced influenza-specific IgA that persisted for at least 6 months. Regulation of type I interferon production, toll-like receptor, and pattern recognition receptor signaling pathways were highly upregulated in milk on day 1 following LAIV but not IIV at any time point. Upregulation of innate immunity in human milk may provide timely protection against mucosal infections until antigen-specific immunity develops in the human milk-fed infant.
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Project description:Streptococcus pneumoniae colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting young children and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal controlled human infection by analysing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with data from a concurrent study in younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. However, older adults who were protected from colonization showed increased degranulation of CD8+ T cells, both before and after pneumococcal challenge. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization.
2024-07-12 | GSE261277 | GEO
Project description:Streptococcus pneumoniae (Spn) is a common cause of respiratory infection, but also frequently colonizes the nasopharynx in the absence of disease. We used mass cytometry to study immune cells from nasal biopsy samples collected following experimental human pneumococcal challenge in order to identify immunological mechanisms of control of Spn colonization. Using 37 markers, we characterized 293 nasal immune cell clusters, of which 7 were associated with Spn colonization. B cell and CD8+CD161+ T cell clusters were significantly lower in colonized than in non-colonized subjects. By following a second cohort before and after pneumococcal challenge we observed that B cells were depleted from the nasal mucosa upon Spn colonization. This associated with an expansion of Spn polysaccharide-specific and total plasmablasts in blood. Moreover, increased responses of blood mucosal associated invariant T (MAIT) cells against in vitro stimulation with pneumococcus prior to challenge associated with protection against establishment of Spn colonization and with increased mucosal MAIT cell populations. These results implicate MAIT cells in the protection against pneumococcal colonization and demonstrate that colonization affects mucosal and circulating B cell populations.
| S-EPMC6763269 | biostudies-literature
Project description:Patients with inflammatory bowel disease (IBD) will be assessed for immunologic response to pneumococcal vaccination. Patients with IBD meet criteria as outlined by the Centers for Disease Control (CDC) for pneumococcal vaccination, yet the investigators have found that pneumococcal vaccination in this population is under-utilized. It is unknown whether or not IBD or IBD-related medications impact the immune response to this recommended vaccine.
Three groups of 25 patients each will be recruited. The first group will consist of outpatients with IBD who are receiving infliximab (Remicade TM) while on concommitant immunosuppressive therapy (with either 6MP, azathioprine, or methotrexate). This group is intended to represent a common ‘heavily immunosuppressed’ patient group with IBD.
The second group will consist of patients with IBD seen in our outpatient clinic who are not on any immune-suppressive medications. These patients meet CDC criteria for vaccination by virtue of having a chronic medical illness. The third group will consist of healthy age-matched (to the first group) controls.
After obtaining informed consent, patients will be screened with baseline lab tests including testing for antibodies against pneumococcus. At the baseline visit, patients will also undergo a brief medical history, physical examination, and assessment of their IBD disease activity.
Included patients will then undergo a one-time intramuscular vaccination with 23-valent polysaccharide pneumococcal vaccine (Pneumovax TM). One month later, subjects will return for a blood draw to assess for response to pneumococcal vaccination.
| 2066877 | ecrin-mdr-crc
Project description: Not available
| S-EPMC6515882 | biostudies-literature
Project description:We measured genome-wide transcript abundance patterns in 246 whole blood samples collected from 35 cynomolgus macaques before and after vaccination with a live attenuated tetravalent dengue vaccine (TDV) or PBS (placebo). Animal work was conducted at the Charmany Instructional Facility of the School of Veterinary Medicine, University of Wisconsin-Madison, and all animal procedures were approved by the University of Wisconsin-Madison's Animal Care and Use Committee. Thirty-five adult male, DENV-seronegative cynomolgus macaques from Vietnam were placed in quarantine for 30 days prior to the start of the study. Five groups of animals (n=6 animals per group) received TDV either subcutaneously (SC) in 0.5 mL inocula or intradermally (ID) in 0.1 mL inocula using a needle-free injector (PharmaJet' device) or needle and syringe (N&S). Animals received two doses (same route) of TDV either on the same day (Day 0) or sixty days apart. One group (n=5) received PBS by ID route and needle-free injector. On day 90 after primary vaccination, 3 animals from each group were challenged with 105 PFU wt DENV-2 (New Guinea C strain) or 105 PFU wt DENV-4 (Dominica/81 strain) by SC route using N&S. Whole blood samples were collected for transcriptional profiling from all animals on days -11, -2, 1, 3, 5, and 7 before and after immunization, and for placebo animals on days 88, 91, 93, 95, and 97 before and after wt DENV challenge. Blood samples were drawn into PAXgene Blood RNA tubes and stored at -80'C prior to RNA extraction and processing.
2016-05-10 | GSE72430 | GEO
Project description:BackgroundInfluenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established.MethodsSeventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses.ResultsOnly 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination.ConclusionsProtection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.
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