tetano
Editor, Senior Moderator
Vaccine. 2019 Jul 3. pii: S0264-410X(19)30777-7. doi: 10.1016/j.vaccine.2019.06.016. [Epub ahead of print]
[h=1]Haemagglutinin stability was not the primary cause of the reduced effectiveness of live attenuated influenza vaccine against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.[/h] Parker L[SUP]1[/SUP], Ritter L[SUP]2[/SUP], Wu W[SUP]2[/SUP], Maeso R[SUP]2[/SUP], Bright H[SUP]2[/SUP], Dibben O[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] During the 2013-2014 influenza season, the quadrivalent live attenuated influenza vaccine (QLAIV), had lower than expected vaccine effectiveness (VE) against circulating A/H1N1pdm09 viruses in the USA. The underlying reason proposed for this was that the A/H1N1pdm09 vaccine strain, A/California/07/2009 (A/CA09), had a thermally unstable haemagglutinin (HA) protein. Consequently, a new A/H1N1pdm09 candidate strain, A/Bolivia/559/2013 (A/BOL13), was developed for inclusion in the 2015-2016 QLAIV. A key parameter for selection of A/BOL13 was its more thermostable HA phenotype compared with A/CA09. During the 2015-2016 season, QLAIV containing A/BOL13 was found in some studies to have improved, but still with suboptimal, VE against circulating A/H1N1pdm09 viruses and was not recommended for use by the CDC in the US market in the 2016-2017 influenza season. This suggested that improved HA thermostability had not entirely resolved the reduced VE observed. One hypothesis for this was that, by improving thermostability, the A/BOL13 HA protein had been over-stabilised, compromising its activation at the low endosomal pH required for successful viral entry. Here we demonstrate that, while the A/BOL13 HA protein is more stable than that of A/CA09, its thermal and pH stability were comparable with historically efficacious LAIV strains, suggesting that the HA had not been over-stabilised. Furthermore, studies simulating potential heat exposure during distribution by exposing QLAIV nasal sprayers to 33 ?C for 4 h showed that, while remaining within product specification, A/CA09 viral potency was statistically decreased after 12 weeks at 2-8 ?C. These data suggest that although unfavourable HA protein stability may have contributed to the reduced VE of A/CA09 in 2013-2014, it was unlikely to have affected A/BOL13 in 2015-2016. We conclude that HA stability was not the primary cause of the reduced effectiveness of LAIV against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
[h=4]KEYWORDS:[/h] 2009 pandemic A/H1N1 (A/H1N1pdm09); Haemagglutinin; Influenza; Live attenuated influenza vaccine; Thermostability; Vaccine effectiveness; pH stability
PMID: 31279567 DOI: 10.1016/j.vaccine.2019.06.016
[h=1]Haemagglutinin stability was not the primary cause of the reduced effectiveness of live attenuated influenza vaccine against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.[/h] Parker L[SUP]1[/SUP], Ritter L[SUP]2[/SUP], Wu W[SUP]2[/SUP], Maeso R[SUP]2[/SUP], Bright H[SUP]2[/SUP], Dibben O[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] During the 2013-2014 influenza season, the quadrivalent live attenuated influenza vaccine (QLAIV), had lower than expected vaccine effectiveness (VE) against circulating A/H1N1pdm09 viruses in the USA. The underlying reason proposed for this was that the A/H1N1pdm09 vaccine strain, A/California/07/2009 (A/CA09), had a thermally unstable haemagglutinin (HA) protein. Consequently, a new A/H1N1pdm09 candidate strain, A/Bolivia/559/2013 (A/BOL13), was developed for inclusion in the 2015-2016 QLAIV. A key parameter for selection of A/BOL13 was its more thermostable HA phenotype compared with A/CA09. During the 2015-2016 season, QLAIV containing A/BOL13 was found in some studies to have improved, but still with suboptimal, VE against circulating A/H1N1pdm09 viruses and was not recommended for use by the CDC in the US market in the 2016-2017 influenza season. This suggested that improved HA thermostability had not entirely resolved the reduced VE observed. One hypothesis for this was that, by improving thermostability, the A/BOL13 HA protein had been over-stabilised, compromising its activation at the low endosomal pH required for successful viral entry. Here we demonstrate that, while the A/BOL13 HA protein is more stable than that of A/CA09, its thermal and pH stability were comparable with historically efficacious LAIV strains, suggesting that the HA had not been over-stabilised. Furthermore, studies simulating potential heat exposure during distribution by exposing QLAIV nasal sprayers to 33 ?C for 4 h showed that, while remaining within product specification, A/CA09 viral potency was statistically decreased after 12 weeks at 2-8 ?C. These data suggest that although unfavourable HA protein stability may have contributed to the reduced VE of A/CA09 in 2013-2014, it was unlikely to have affected A/BOL13 in 2015-2016. We conclude that HA stability was not the primary cause of the reduced effectiveness of LAIV against A/H1N1pdm09 viruses in the 2013-2014 and 2015-2016 seasons.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
[h=4]KEYWORDS:[/h] 2009 pandemic A/H1N1 (A/H1N1pdm09); Haemagglutinin; Influenza; Live attenuated influenza vaccine; Thermostability; Vaccine effectiveness; pH stability
PMID: 31279567 DOI: 10.1016/j.vaccine.2019.06.016