tetano
Editor, Senior Moderator
Vaccine. 2020 May 3. pii: S0264-410X(20)30462-X. doi: 10.1016/j.vaccine.2020.04.004. [Epub ahead of print]
Replication of live attenuated influenza vaccine viruses in human nasal epithelial cells is associated with H1N1 vaccine effectiveness.
Hawksworth A[SUP]1[/SUP], Lockhart R[SUP]1[/SUP], Crowe J[SUP]1[/SUP], Maeso R[SUP]1[/SUP], Ritter L[SUP]1[/SUP], Dibben O[SUP]1[/SUP], Bright H[SUP]2[/SUP].
Author information
Abstract
In the 2013-2014 and 2015-2016 influenza seasons, live attenuated influenza vaccine (LAIV) generated reduced vaccine effectiveness (VE) against circulating H1N1 strains. This reduced VE coincided with the introduction of pandemic 2009 H1N1 (A/H1N1pdm09) vaccine virus reassortants, in place of pre-2009 seasonal H1N1 strains. Here, we explored one specific hypothesis for reduced VE; decreased replicative fitness of A/H1N1pdm09 strains in humans. Two A/H1N1pdm09 strains with reduced VE, A/California/07/2009 (A/CA09) and A/Bolivia/559/2013 (A/BOL13), were compared to pre-2009 seasonal H1N1 strains, A/New Caledonia/20/1999 (A/NC99) and A/South Dakota/6/2007 (A/SD07). Initial results showed that A/H1N1pdm09 strains had reduced multi-cycle infectivity in Madin-Darby Canine Kidney (MDCK) cells, compared to their pre-2009 counterparts. The A/BOL13 viral titre was found to be 2.65 log[SUB]10[/SUB]/mL lower when measured by multi-cycle 50% tissue culture infectious dose (TCID[SUB]50[/SUB]) assay compared to single-cycle fluorescent focus assay (FFA). By contrast, clinically effective A/NC99 titres differed by only 0.54 log[SUB]10[/SUB]/mL. In human alveolar (A549) cells, A/H1N1pdm09 strains replicated less than pre-2009 strains, with A/CA09 and A/BOL13 generating lower peak viral titres over 5 days. This phenotype was corroborated in physiologically relevant, primary human nasal epithelial cells (hNECs). Here, peak titres for pre-2009 strains A/NC99 and A/SD07 were 8.43 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL and 8.52 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL, respectively, versus 6.89 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL and 6.06 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL for A/H1N1pdm09 strains A/CA09 and A/BOL13. This confirmed a reduced ability of A/H1N1pdm09 strains to sustain replication in human respiratory cells. Using this information, H1N1 candidate A/Slovenia/2903/2015 (A/SLOV15) was characterised for replacement of A/BOL13 in the 2017/18 LAIV. A/SLOV15 produced comparable single and multi-cycle infectivity titres (Δ 0.16 log[SUB]10[/SUB]/mL) and reached a peak titre 1.23 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL higher than that of A/BOL13 in hNEC cultures. Taken together, these data suggest a reduction in sustained multi-cycle replication in human cells as a plausible root cause for reduced A/H1N1pdm09 VE.
Copyright ? 2020 Elsevier Ltd. All rights reserved.
PMID:32376111DOI:10.1016/j.vaccine.2020.04.004
Replication of live attenuated influenza vaccine viruses in human nasal epithelial cells is associated with H1N1 vaccine effectiveness.
Hawksworth A[SUP]1[/SUP], Lockhart R[SUP]1[/SUP], Crowe J[SUP]1[/SUP], Maeso R[SUP]1[/SUP], Ritter L[SUP]1[/SUP], Dibben O[SUP]1[/SUP], Bright H[SUP]2[/SUP].
Author information
Abstract
In the 2013-2014 and 2015-2016 influenza seasons, live attenuated influenza vaccine (LAIV) generated reduced vaccine effectiveness (VE) against circulating H1N1 strains. This reduced VE coincided with the introduction of pandemic 2009 H1N1 (A/H1N1pdm09) vaccine virus reassortants, in place of pre-2009 seasonal H1N1 strains. Here, we explored one specific hypothesis for reduced VE; decreased replicative fitness of A/H1N1pdm09 strains in humans. Two A/H1N1pdm09 strains with reduced VE, A/California/07/2009 (A/CA09) and A/Bolivia/559/2013 (A/BOL13), were compared to pre-2009 seasonal H1N1 strains, A/New Caledonia/20/1999 (A/NC99) and A/South Dakota/6/2007 (A/SD07). Initial results showed that A/H1N1pdm09 strains had reduced multi-cycle infectivity in Madin-Darby Canine Kidney (MDCK) cells, compared to their pre-2009 counterparts. The A/BOL13 viral titre was found to be 2.65 log[SUB]10[/SUB]/mL lower when measured by multi-cycle 50% tissue culture infectious dose (TCID[SUB]50[/SUB]) assay compared to single-cycle fluorescent focus assay (FFA). By contrast, clinically effective A/NC99 titres differed by only 0.54 log[SUB]10[/SUB]/mL. In human alveolar (A549) cells, A/H1N1pdm09 strains replicated less than pre-2009 strains, with A/CA09 and A/BOL13 generating lower peak viral titres over 5 days. This phenotype was corroborated in physiologically relevant, primary human nasal epithelial cells (hNECs). Here, peak titres for pre-2009 strains A/NC99 and A/SD07 were 8.43 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL and 8.52 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL, respectively, versus 6.89 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL and 6.06 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL for A/H1N1pdm09 strains A/CA09 and A/BOL13. This confirmed a reduced ability of A/H1N1pdm09 strains to sustain replication in human respiratory cells. Using this information, H1N1 candidate A/Slovenia/2903/2015 (A/SLOV15) was characterised for replacement of A/BOL13 in the 2017/18 LAIV. A/SLOV15 produced comparable single and multi-cycle infectivity titres (Δ 0.16 log[SUB]10[/SUB]/mL) and reached a peak titre 1.23 log[SUB]10[/SUB] TCID[SUB]50[/SUB]/mL higher than that of A/BOL13 in hNEC cultures. Taken together, these data suggest a reduction in sustained multi-cycle replication in human cells as a plausible root cause for reduced A/H1N1pdm09 VE.
Copyright ? 2020 Elsevier Ltd. All rights reserved.
PMID:32376111DOI:10.1016/j.vaccine.2020.04.004