Intranasal vaccine induces broad and long-lasting immunity against the hemagglutinin stem of group 2 influenza A viruses
Bibliographic record
Abstract
Influenza A viruses are categorized into two phylogenetic groups (group 1 and group 2) based on the structure of their hemagglutinin (HA) protein. Within group 2, H3N2 poses a particular challenge due to its rapid evolution, limited vaccine efficacy, and association with more severe influenza seasons. Although T cell responses have been extensively studied in the context of vaccine-induced protection, HA stem (HA2)-specific T cell responses have been relatively understudied, especially those related to nasal immunity. To address this, we engineered an adenoviral vector vaccine (Ad-HA2) expressing a consensus hemagglutinin stem sequence, derived through bioinformatic analysis of all H3 strains. The vaccine conferred heterosubtypic protection against lethal challenges with either H3N2 or H7N9, both belonging to group 2 influenza A viruses, with protection lasting at least six months post-vaccination. Notably, the vaccine induced robust HA2-specific humoral and cell-mediated responses in the nasal-associated lymphoid tissue (NALT) of the upper respiratory tract, the first line of immune defense against inhaled pathogens. The vaccine also elicited significant levels of antibodies and T cell responses in the lower respiratory tract and pulmonary immune sites. Furthermore, circulating antibodies in the serum demonstrated effective antibody-dependent cellular cytotoxicity (ADCC) activity. Finally, using a peptide pool matrix screening approach combined with in silico verification, we identified an immunogenic C-terminus region of the HA2 consensus sequence that activated CD4+ and CD8+ T cells, which warrants further investigation. Collectively, these findings are informative for the design and evaluation of mucosal influenza vaccines targeting the hemagglutinin stem. • The consensus hemagglutinin stem (HA2) sequence derived from all H3 strains was designed for a novel influenza vaccine. • The vaccine conferred heterosubtypic protection against H3N2 or H7N9 challenges, both group 2 influenza A viruses. • The vaccine induced robust HA2-specific humoral and cell-mediated responses in upper and lower respiratory tract. • An immunogenic region that activated CD4+ and CD8+ T cells was identified, which warrants further investigation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".