tetano
Editor, Senior Moderator
J Virol. 2016 May 11. pii: JVI.00093-16. [Epub ahead of print]
[h=1]Association between HA stem-reactive antibodies and influenza A/H1N1 infection during the 2009 pandemic.[/h] Hoa LN[SUP]1[/SUP], Mai LQ[SUP]2[/SUP], Bryant JE[SUP]3[/SUP], Thai PQ[SUP]2[/SUP], Hang NL[SUP]2[/SUP], Yen NT[SUP]2[/SUP], Duong TN[SUP]2[/SUP], Thoang DD[SUP]4[/SUP], Horby P[SUP]3[/SUP], Werheim HF[SUP]5[/SUP], Fox A[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The discovery of influenza broadly neutralizing antibodies prompted efforts to develop universal vaccines. Influenza virus stem-reactive (SR), broadly-neutralizing (BrN) antibodies have been detected by screening antibody phage display libraries. However, studies of SR-BrN antibodies in human serum, and their association with natural infection, are limited. To address this, pre- and post-pandemic sera from a prospective community cohort study in Viet Nam were assessed for antibodies that inhibit SR-BrN mAb (C179) binding to H1N1 pandemic 2009 virus (H1N1pdm09). Of 270 households, 33 with at least one confirmed H1N1pdm09 illness, or at least two seroconverters were included. The included households comprised 71 infected and 41 non-infected participants. Sera were tested as two-fold dilutions between 1:5 and 1:40. 50% C179 inhibition (IC50) titers did not exceed 10, although both IC50 titers, and % C179 inhibition by sera diluted 1:5 or 1:10, correlated with HI and MN titers (all p < 0.001). Thirteen (12%) participants had detectable pre-pandemic IC50 titers but only one reached a titer of 10. This proportion increased to 44% after the pandemic when 39 participants had a titer of 10, and 67% of infected compared to 44% of non-infected had detectable IC50 titers (p < 0.001). The low levels of SR-reactive antibodies in pre-pandemic sera were not associated with subsequent H1N1pdm09 infection (p = 0.241), and the higher levels induced by H1N1pdm09 infection returned to pre-pandemic levels within two years. The findings indicate that natural infection induces only low titers of SR antibodies that are not sustained.
[h=4]IMPORTANCE:[/h] Universal influenza vaccines could have substantial health and economic benefits. The focus of universal vaccine research has been to induce antibodies that prevent infection by diverse influenza strains. These so-called broadly-neutralizing antibodies are readily detected in mice and ferrets after infection with a series of distinct influenza strains. The 2009 H1N1 pandemic provided an opportunity to investigate whether infection with a novel strain induced broadly-neutralizing antibodies in humans. We found that broadly neutralizing antibodies were induced, but levels were low and poorly maintained. This could represent an obstacle for universal vaccine development and warrants further investigation.
Copyright ? 2016 Hoa et al.
PMID: 27170747 [PubMed - as supplied by publisher] Free full text
[h=1]Association between HA stem-reactive antibodies and influenza A/H1N1 infection during the 2009 pandemic.[/h] Hoa LN[SUP]1[/SUP], Mai LQ[SUP]2[/SUP], Bryant JE[SUP]3[/SUP], Thai PQ[SUP]2[/SUP], Hang NL[SUP]2[/SUP], Yen NT[SUP]2[/SUP], Duong TN[SUP]2[/SUP], Thoang DD[SUP]4[/SUP], Horby P[SUP]3[/SUP], Werheim HF[SUP]5[/SUP], Fox A[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The discovery of influenza broadly neutralizing antibodies prompted efforts to develop universal vaccines. Influenza virus stem-reactive (SR), broadly-neutralizing (BrN) antibodies have been detected by screening antibody phage display libraries. However, studies of SR-BrN antibodies in human serum, and their association with natural infection, are limited. To address this, pre- and post-pandemic sera from a prospective community cohort study in Viet Nam were assessed for antibodies that inhibit SR-BrN mAb (C179) binding to H1N1 pandemic 2009 virus (H1N1pdm09). Of 270 households, 33 with at least one confirmed H1N1pdm09 illness, or at least two seroconverters were included. The included households comprised 71 infected and 41 non-infected participants. Sera were tested as two-fold dilutions between 1:5 and 1:40. 50% C179 inhibition (IC50) titers did not exceed 10, although both IC50 titers, and % C179 inhibition by sera diluted 1:5 or 1:10, correlated with HI and MN titers (all p < 0.001). Thirteen (12%) participants had detectable pre-pandemic IC50 titers but only one reached a titer of 10. This proportion increased to 44% after the pandemic when 39 participants had a titer of 10, and 67% of infected compared to 44% of non-infected had detectable IC50 titers (p < 0.001). The low levels of SR-reactive antibodies in pre-pandemic sera were not associated with subsequent H1N1pdm09 infection (p = 0.241), and the higher levels induced by H1N1pdm09 infection returned to pre-pandemic levels within two years. The findings indicate that natural infection induces only low titers of SR antibodies that are not sustained.
[h=4]IMPORTANCE:[/h] Universal influenza vaccines could have substantial health and economic benefits. The focus of universal vaccine research has been to induce antibodies that prevent infection by diverse influenza strains. These so-called broadly-neutralizing antibodies are readily detected in mice and ferrets after infection with a series of distinct influenza strains. The 2009 H1N1 pandemic provided an opportunity to investigate whether infection with a novel strain induced broadly-neutralizing antibodies in humans. We found that broadly neutralizing antibodies were induced, but levels were low and poorly maintained. This could represent an obstacle for universal vaccine development and warrants further investigation.
Copyright ? 2016 Hoa et al.
PMID: 27170747 [PubMed - as supplied by publisher] Free full text