A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity
| Autor: | Neena Kashyap, Stephen A. Migueles, April Poole, Alyssa A. Pullano, Jinghe Huang, Mark Connors, Marc Gurwith, Florian Krammer, C. Jason Liang, Daniel Stadlbauer, Sarah Stuccio, Kenta Matsuda, Jessica Pederson, Jeff Alexander, Byong H. Kang, Kelly M. Martins, Angelique Biancotto, Sean Evans, Lyuba Bolkhovitinov, Tulley Shofner, Elise Ishida, Nathaniel E Wright, Julián Candia, Trevor Griesman, Matthew G. Zimmerman, Andy Patamawenu, Jon Smith, Giovanna Fantoni |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Male Adolescent Influenza vaccine Genetic Vectors Palatine Tonsil Administration Oral Hemagglutinin Glycoproteins Influenza Virus Antibodies Viral Virus Replication 03 medical and health sciences Young Adult 0302 clinical medicine Immune system Antigen Immunity Influenza Human Medicine Humans Viral shedding Antigens Viral Immunity Mucosal Immunity Cellular Influenza A Virus H5N1 Subtype business.industry Adenoviruses Human General Medicine Nasal Sprays Influenza research Acquired immune system Antibodies Neutralizing Immunity Humoral Virus Shedding Vaccination 030104 developmental biology Influenza Vaccines 030220 oncology & carcinogenesis Immunology Female Clinical Medicine business |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| Popis: | BACKGROUND: To understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray. METHODS: Viral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays. RESULTS: Ad4-H5-Vtn DNA was shed from most upper respiratory tract–immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4(+) and CD8(+) T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine. CONCLUSION: Replicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT01443936 and NCT01806909. FUNDING: Intramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C). |
| Databáze: | OpenAIRE |
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