Current Status of Live Attenuated Influenza Vaccine in the United States for Seasonal and Pandemic Influenza

Christopher S. Ambrose; Catherine Luke; Kathleen Coelingh


Influenza Resp Viruses. 2008;2(6):193-202. 

In This Article

H5N1 Pandemic LAIV

To date, NIH and MedImmune have generated three candidate pLAIV viruses of the H5N1 subtype that derive their HA and NA from H5N1 influenza viruses isolated from humans in Hong Kong in 1997, Hong Kong in 2003, and Vietnam in 2004. In all cases, the HA was modified to remove the multibasic cleavage site. As a result of this modification, all three vaccine viruses were of a low pathogenicity phenotype in chickens. The vaccine viruses were restricted in replication in the respiratory tract of mice and attenuated in ferrets, consistent with the att phenotype of the MDV. Toxicologic evaluation of H5N1 ca vaccine viruses in ferrets revealed no evidence of systemic toxicity following repeated intranasal administration.[48] Vaccination with a single dose of H5N1 AA ca vaccine administered intranasally protected mice against lethal challenge with wild-type virus, but two doses administered intranasally were required to elicit detectable serum HAI and neutralizing antibodies in mice and ferrets and to protect against pulmonary replication of wild-type viruses.[49] In addition, vaccination of mice with two doses of H5N1 ca vaccine protected mice against pulmonary replication of antigenically distinct heterologous wild-type H5N1 viruses, suggesting that such vaccines may elicit broadly cross-reactive immune responses. The H5N1 pLAIV viruses with the HA and NA from influenza A/Vietnam/1203/2004 (H5N1) and influenza A/Hong Kong/213/2003 (H5N1) have been evaluated for safety, infectivity, and immunogenicity in phase I clinical trials (data on file).


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