Journal
VACCINE
Volume 26, Issue 29-30, Pages 3580-3586Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2008.05.001
Keywords
influenza; NS gene; NS1 protein; live-attenuated vaccine
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Funding
- NIAID NIH HHS [U01 AI070469, R01 AI46954, U01 AI070469-01, R01 AI046954-01A1, R01 AI046954] Funding Source: Medline
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From a stock of A/turkey/Oregon/71-delNS1 (H7N3) virus, which has a 10 nucleotide deletion in the coding region of the NS1 gene, we found that several variants with different sizes of NS genes could be produced by passaging the virus in 10- and 14-day-old embryonating chicken eggs (ECE), but not in 7-day-old ECE or Vero cells. We were able to rescue the reassortant virus that has different sizes of the NS genes and confirmed that those NS genes are genetically stable. By conducting in vivo studies in 2-week-old chickens, we found two plaque purified variants (D-del pc3 and pc4) which can be used as a potential live-attenuated vaccine. The variants were highly attenuated in chickens and did not transmit the virus from infected chickens to uninoculated cage mates. At the same time, the variants induced relatively high antibody titers which conferred good protection against a high dose heterologous virus challenge. Our study indicates that naturally selected NS1 deletion variants might be useful in the development of live-attenuated influenza vaccines in poultry. Furthermore, deletion in the NS1 protein can be potentially useful as a negative marker for a differentiating infected from vaccinated animals (DIVA) approach. (C) 2008 Elsevier Ltd. All rights reserved.
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