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
| Action | DRS | |||
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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.
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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.
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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.
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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