Trial reportThe Journal of clinical investigation2021
A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 54 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1 Study of Safety and Immunogenicity of Ad4-H5-VTN in Ad4 Seronegative and Seropositive Volunteers
Phase 1 Study of Safety and Immunogenicity of Intranasal Ad4-H5-VTN in Ad4 Seronegative and Seropositive Volunteers
Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Mucosal immunity and vaccine development.Signal transduction and targeted therapy · 2026Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Safety and immunogenicity of an HIV vaccine trial with DNA prime and replicating vaccinia boost.Signal transduction and targeted therapy · 2025Trial
- Article
- Transgene Expression Kinetics and Replication Potential of Recombinant Adenovirus Serotype 4 in a Mouse Model and its Use as a Herpes Simplex Virus Vaccine.bioRxiv : the preprint server for biology · 2026Article
- Gut Microbiota and Probiotics in Influenza: A Narrative Review of Mechanisms and Emerging Evidence.Viruses · 2026Review
- Nasal humoral immunity: the first line of protection against respiratory pathogens.ImmunoHorizons · 2026Review
- Intranasal replicating adenovirus type 4-vectored SARS-CoV-2 vaccines induce durable and efficacious responses in preclinical testing.iScience · 2026Article
- A semi-replicating VSV (srVSV)-based platform for developing broad-spectrum mucosal vaccines against influenza A viruses.Virologica Sinica · 2026Article
- Intranasal Replicating Adenovirus type 4-SARS-CoV-2 Recombinants Induce Superior Immune Response Durability and Efficacy in Preclinical Testing Compared to Standard Intramuscular Vaccines.bioRxiv : the preprint server for biology · 2026Article
- Applications of Pseudoviruses Bearing Glycoproteins of SARS-CoV-2 and Influenza Virus.Advances in experimental medicine and biology · 2026Review
- Immunological and virological questions for H5N1 pandemic emergence.ImmunoHorizons · 2025Review
- Development of a broad-spectrum nasal live attenuated influenza vaccine based on mosaic antigen design against influenza B viruses.Emerging microbes & infections · 2025Article
- Developing the next-generation of adenoviral vector vaccines.Human vaccines & immunotherapeutics · 2025Review
- Four decades of adenovirus gene transfer vectors: History and current use.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Clinical Translation Challenges and Strategies for Tumour Vaccines Considering Multiple Delivery Routes.Vaccines · 2025Review
- Human saliva exerts strong type-dependent effects on adenovirus infectivity.Frontiers in immunology · 2025Article
- Review
- Low-level human memory T and B cells recognising avian influenza hemagglutinins are poorly responsive to existing seasonal influenza vaccines.Clinical & translational immunology · 2025Article
- Multifaceted virus-like particles: Navigating towards broadly effective influenza A virus vaccines.Current research in microbial sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUNDTo 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.METHODSViral 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.RESULTSAd4-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.CONCLUSIONReplicating 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 REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural 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).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.