tetano
Editor, Senior Moderator
MBio. 2018 Jan 23;9(1). pii: e02284-17. doi: 10.1128/mBio.02284-17.
[h=1]Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus.[/h] Park JK[SUP]1[/SUP], Han A[SUP]1[/SUP], Czajkowski L[SUP]1[/SUP], Reed S[SUP]1[/SUP], Athota R[SUP]1[/SUP], Bristol T[SUP]1[/SUP], Rosas LA[SUP]1[/SUP], Cervantes-Medina A[SUP]1[/SUP], Taubenberger JK[SUP]1[/SUP], Memoli MJ[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay (ELISA) was performed on samples from 65 participants challenged with a 2009 H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated with multiple outcome measures to evaluate anti-HA stalk antibody titer as a correlate of protection. Anti-HA stalk antibody titers were present before challenge and rose in response to challenge in 64% of individuals. Those individuals with higher titers at baseline were less likely to develop shedding, but not less likely to develop symptoms. Similar to the hemagglutination inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not independently predict a decrease in the severity of influenza disease, while the antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of protection, the naturally occurring anti-HA stalk antibody titer is predictive of a reduction of certain aspects of disease similar to HAI titer, but the NAI titer is the only identified correlate that is an independent predictor of a reduction of all assessed influenza clinical outcome measures.IMPORTANCE This is the first study to evaluate preexisting anti-HA stalk antibodies as a predictor of protection. We use a healthy volunteer influenza challenge trial for an examination of the role such antibodies play in protection. This study demonstrates that anti-HA stalk antibodies are naturally generated in response to an infection, but there is significant variability in response. Similar to antibodies that target the HA head, baseline anti-HA stalk antibody titer is a correlate of protection in terms of reduced shedding, but it is not a predictor of reduced clinical disease or an independent predictor of disease severity. These results, in the context of the limited data available in humans, suggest that vaccines that induce anti-HA stalk antibodies could play a role in future vaccine strategies, but alone, this target may be insufficient to induce a fully protective vaccine and overcome some of the issues identified with current vaccines.
[h=4]KEYWORDS:[/h] CHIM; HA stalk; NA; antibody; human challenge; influenza; influenza A; neuraminidase; universal vaccine
PMID: 29362240 DOI: 10.1128/mBio.02284-17
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[h=1]Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus.[/h] Park JK[SUP]1[/SUP], Han A[SUP]1[/SUP], Czajkowski L[SUP]1[/SUP], Reed S[SUP]1[/SUP], Athota R[SUP]1[/SUP], Bristol T[SUP]1[/SUP], Rosas LA[SUP]1[/SUP], Cervantes-Medina A[SUP]1[/SUP], Taubenberger JK[SUP]1[/SUP], Memoli MJ[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary target of licensed influenza vaccines. Recently, broadly reactive antibodies that target the stalk region of the HA have become a major focus of current novel vaccine development. These antibodies have been observed in humans after natural infection with influenza A virus, but the data are limited. Using samples and data from the uniquely controlled setting of an influenza A/H1N1 virus human challenge study of healthy volunteers, we performed a secondary analysis that for the first time explores the role of anti-HA stalk antibody as a human correlate of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay (ELISA) was performed on samples from 65 participants challenged with a 2009 H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated with multiple outcome measures to evaluate anti-HA stalk antibody titer as a correlate of protection. Anti-HA stalk antibody titers were present before challenge and rose in response to challenge in 64% of individuals. Those individuals with higher titers at baseline were less likely to develop shedding, but not less likely to develop symptoms. Similar to the hemagglutination inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not independently predict a decrease in the severity of influenza disease, while the antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of protection, the naturally occurring anti-HA stalk antibody titer is predictive of a reduction of certain aspects of disease similar to HAI titer, but the NAI titer is the only identified correlate that is an independent predictor of a reduction of all assessed influenza clinical outcome measures.IMPORTANCE This is the first study to evaluate preexisting anti-HA stalk antibodies as a predictor of protection. We use a healthy volunteer influenza challenge trial for an examination of the role such antibodies play in protection. This study demonstrates that anti-HA stalk antibodies are naturally generated in response to an infection, but there is significant variability in response. Similar to antibodies that target the HA head, baseline anti-HA stalk antibody titer is a correlate of protection in terms of reduced shedding, but it is not a predictor of reduced clinical disease or an independent predictor of disease severity. These results, in the context of the limited data available in humans, suggest that vaccines that induce anti-HA stalk antibodies could play a role in future vaccine strategies, but alone, this target may be insufficient to induce a fully protective vaccine and overcome some of the issues identified with current vaccines.
[h=4]KEYWORDS:[/h] CHIM; HA stalk; NA; antibody; human challenge; influenza; influenza A; neuraminidase; universal vaccine
PMID: 29362240 DOI: 10.1128/mBio.02284-17
Free full text