Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans
Background Adenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized, and its ability to induce mucosal immunity in huma...
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-02-01
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| Series: | JCI Insight |
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| Online Access: | https://doi.org/10.1172/jci.insight.155655 |
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| author | Mangalakumari Jeyanathan Dominik K. Fritz Sam Afkhami Emilio Aguirre Karen J. Howie Anna Zganiacz Anna Dvorkin-Gheva Michael R. Thompson Richard F. Silver Ruth P. Cusack Brian D. Lichty Paul M. O’Byrne Martin Kolb Maria Fe C. Medina Myrna B. Dolovich Imran Satia Gail M. Gauvreau Zhou Xing Fiona Smaill |
| author_facet | Mangalakumari Jeyanathan Dominik K. Fritz Sam Afkhami Emilio Aguirre Karen J. Howie Anna Zganiacz Anna Dvorkin-Gheva Michael R. Thompson Richard F. Silver Ruth P. Cusack Brian D. Lichty Paul M. O’Byrne Martin Kolb Maria Fe C. Medina Myrna B. Dolovich Imran Satia Gail M. Gauvreau Zhou Xing Fiona Smaill |
| author_sort | Mangalakumari Jeyanathan |
| collection | DOAJ |
| description | Background Adenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized, and its ability to induce mucosal immunity in humans is unknown. This phase Ib trial evaluated the safety and immunogenicity of human serotype-5 Ad-vectored tuberculosis (TB) vaccine (AdHu5Ag85A) delivered to humans via inhaled aerosol or i.m. injection.Methods Thirty-one healthy, previously BCG-vaccinated adults were enrolled. AdHu5Ag85A was administered by single-dose aerosol using Aeroneb Solo Nebulizer or by i.m. injection. The study consisted of the low-dose (LD) aerosol, high-dose (HD) aerosol, and i.m. groups. The adverse events were assessed at various times after vaccination. Immunogenicity data were collected from the peripheral blood and bronchoalveolar lavage samples at baseline, as well as at select time points after vaccination.Results The nebulized aerosol droplets were < 5.39 μm in size. Both LD and HD of AdHu5Ag85A administered by aerosol inhalation and i.m. injection were safe and well tolerated. Both aerosol doses, particularly LD, but not i.m., vaccination markedly induced airway tissue–resident memory CD4+ and CD8+ T cells of polyfunctionality. While as expected, i.m. vaccination induced Ag85A-specific T cell responses in the blood, the LD aerosol vaccination also elicited such T cells in the blood. Furthermore, the LD aerosol vaccination induced persisting transcriptional changes in alveolar macrophages.Conclusion Inhaled aerosol delivery of Ad-vectored vaccine is a safe and superior way to elicit respiratory mucosal immunity. This study warrants further development of aerosol vaccine strategies against respiratory pathogens, including TB and COVID-19.Trial registration ClinicalTrial.gov, NCT02337270.Funding The Canadian Institutes for Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada funded this work. |
| first_indexed | 2024-12-12T08:29:10Z |
| format | Article |
| id | doaj.art-0f5b7f6ff7fa419a8108b00742172faf |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:29:10Z |
| publishDate | 2022-02-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-0f5b7f6ff7fa419a8108b00742172faf2022-12-22T00:31:09ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-02-0173Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humansMangalakumari JeyanathanDominik K. FritzSam AfkhamiEmilio AguirreKaren J. HowieAnna ZganiaczAnna Dvorkin-GhevaMichael R. ThompsonRichard F. SilverRuth P. CusackBrian D. LichtyPaul M. O’ByrneMartin KolbMaria Fe C. MedinaMyrna B. DolovichImran SatiaGail M. GauvreauZhou XingFiona SmaillBackground Adenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity. However, aerosol delivery of Ad-vectored vaccines remains poorly characterized, and its ability to induce mucosal immunity in humans is unknown. This phase Ib trial evaluated the safety and immunogenicity of human serotype-5 Ad-vectored tuberculosis (TB) vaccine (AdHu5Ag85A) delivered to humans via inhaled aerosol or i.m. injection.Methods Thirty-one healthy, previously BCG-vaccinated adults were enrolled. AdHu5Ag85A was administered by single-dose aerosol using Aeroneb Solo Nebulizer or by i.m. injection. The study consisted of the low-dose (LD) aerosol, high-dose (HD) aerosol, and i.m. groups. The adverse events were assessed at various times after vaccination. Immunogenicity data were collected from the peripheral blood and bronchoalveolar lavage samples at baseline, as well as at select time points after vaccination.Results The nebulized aerosol droplets were < 5.39 μm in size. Both LD and HD of AdHu5Ag85A administered by aerosol inhalation and i.m. injection were safe and well tolerated. Both aerosol doses, particularly LD, but not i.m., vaccination markedly induced airway tissue–resident memory CD4+ and CD8+ T cells of polyfunctionality. While as expected, i.m. vaccination induced Ag85A-specific T cell responses in the blood, the LD aerosol vaccination also elicited such T cells in the blood. Furthermore, the LD aerosol vaccination induced persisting transcriptional changes in alveolar macrophages.Conclusion Inhaled aerosol delivery of Ad-vectored vaccine is a safe and superior way to elicit respiratory mucosal immunity. This study warrants further development of aerosol vaccine strategies against respiratory pathogens, including TB and COVID-19.Trial registration ClinicalTrial.gov, NCT02337270.Funding The Canadian Institutes for Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada funded this work.https://doi.org/10.1172/jci.insight.155655Infectious diseaseVaccines |
| spellingShingle | Mangalakumari Jeyanathan Dominik K. Fritz Sam Afkhami Emilio Aguirre Karen J. Howie Anna Zganiacz Anna Dvorkin-Gheva Michael R. Thompson Richard F. Silver Ruth P. Cusack Brian D. Lichty Paul M. O’Byrne Martin Kolb Maria Fe C. Medina Myrna B. Dolovich Imran Satia Gail M. Gauvreau Zhou Xing Fiona Smaill Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans JCI Insight Infectious disease Vaccines |
| title | Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans |
| title_full | Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans |
| title_fullStr | Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans |
| title_full_unstemmed | Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans |
| title_short | Aerosol delivery, but not intramuscular injection, of adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans |
| title_sort | aerosol delivery but not intramuscular injection of adenovirus vectored tuberculosis vaccine induces respiratory mucosal immunity in humans |
| topic | Infectious disease Vaccines |
| url | https://doi.org/10.1172/jci.insight.155655 |
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