Cross-protection against highly pathogenic avian influenza H5N1 virus from seasonal influenza vaccines: a systematic review and meta-analysis of ferret studies.
IShin Tseng, Ying-Chi Huang, Wei-Liang Shih et al.
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In 30 seconds
This systematic review and meta-analysis assessed whether seasonal influenza vaccines protect ferrets against mortality after lethal H5N1 challenge. Across 35 studies comprising 157 trials, seasonal vaccines without an N1 component showed no significant cross-protection (VE 14.8%, 95% CI -3.6 to 30.0). N1-containing seasonal vaccines had VE of 73% (19 trials; 95% CI 54-84), compared with 77% for H5N1 vaccines overall (133 trials; 95% CI 72-82; p = 0.52). The findings indicate cross-protection in ferrets when seasonal vaccines contain N1, but do not establish protection in humans.
Key findings
- Seasonal influenza vaccines without N1 had VE 14.8% (95% CI -3.6 to 30.0) against H5N1-related mortality across five trials.
- N1-containing seasonal vaccines had VE 73% (95% CI 54-84) across 19 trials.
- Overall H5N1 vaccine VE was 77% (95% CI 72-82); its difference from N1-containing seasonal vaccines was not significant (p = 0.52).
- N1-containing seasonal vaccine VE was lower than that of seroprotective H5N1 vaccines (88%; 95% CI 84-91; p = 0.009), but comparable to H5N1 vaccines without seroprotection (63%; 95% CI 52-71; p = 0.29).
Why it matters
The results suggest that seasonal vaccines containing an N1 component may reduce H5N1-associated mortality in ferrets, a relevant finding while human H5N1 vaccines are unavailable in most countries. However, animal challenge results cannot establish clinical protection in people. The review therefore identifies a potential cross-protection signal and a rationale for human studies, rather than evidence of human vaccine effectiveness.
What to keep in mind
Evidence comes from ferret challenge trials, so the findings do not establish protection in humans.