tetano
Editor, Senior Moderator
J Virol. 2014 Aug 13. pii: JVI.01107-14. [Epub ahead of print]
The matrix gene segment destabilizes the acid and thermal stability of the hemagglutinin of pandemic live attenuated influenza virus vaccines.
O'Donnell CD1, Vogel L1, Matsuoka Y1, Jin H2, Subbarao K3.
Author information
Abstract
The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated 7 reassortant pandemic live attenuated influenza vaccines (pLAIV) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the 6 internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIVs were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and although they shared the same backbone, the pLAIVs had a lower shut off temperature than seasonal LAIVs, suggesting the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low pathogenicity avian influenza viruses, as reported by others. However, pLAIVs had a consistently higher pH of HA activation and reduced HA thermostability compared with the corresponding wild-type parental viruses. From studies with single gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIVs we observed in seronegative adults.
SIGNIFICANCE:
There is increasing evidence that HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccines (pLAIVs) and observed that the pLAIVs consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIVs may account for their restricted replication in clinical trials.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25122789
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25122789
The matrix gene segment destabilizes the acid and thermal stability of the hemagglutinin of pandemic live attenuated influenza virus vaccines.
O'Donnell CD1, Vogel L1, Matsuoka Y1, Jin H2, Subbarao K3.
Author information
Abstract
The threat of future influenza pandemics and their potential for rapid spread, morbidity, and mortality has led to the development of pandemic vaccines. We generated 7 reassortant pandemic live attenuated influenza vaccines (pLAIV) with the hemagglutinin (HA) and neuraminidase (NA) genes derived from animal influenza viruses on the backbone of the 6 internal protein gene segments of the temperature sensitive, cold-adapted (ca) A/Ann Arbor/60 (H2N2) virus (AA/60 ca) of the licensed seasonal LAIV. The pLAIVs were moderately to highly restricted in replication in seronegative adults; we sought to determine the biological basis for this restriction. Avian influenza viruses generally replicate at higher temperatures than human influenza viruses and although they shared the same backbone, the pLAIVs had a lower shut off temperature than seasonal LAIVs, suggesting the HA and NA influence the degree of temperature sensitivity. The pH of HA activation of highly pathogenic avian influenza viruses was greater than human and low pathogenicity avian influenza viruses, as reported by others. However, pLAIVs had a consistently higher pH of HA activation and reduced HA thermostability compared with the corresponding wild-type parental viruses. From studies with single gene reassortant viruses bearing one gene segment from the AA/60 ca virus in recombinant H5N1 or pH1N1 viruses, we found that the lower HA thermal stability and increased pH of HA activation were associated with the AA/60 M gene. Together, the impaired HA acid and thermal stability and temperature sensitivity likely contributed to the restricted replication of the pLAIVs we observed in seronegative adults.
SIGNIFICANCE:
There is increasing evidence that HA stability of influenza viruses depends on the virus strain and host species and that HA stability can influence replication, virulence, and transmission of influenza A viruses in different species. We investigated the HA stability of pandemic live attenuated influenza vaccines (pLAIVs) and observed that the pLAIVs consistently had a less stable HA than the corresponding wild-type influenza viruses. The reduced HA stability and temperature sensitivity of the pLAIVs may account for their restricted replication in clinical trials.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25122789
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25122789