Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination

Nathalie Loeb; Melissa K. Andrew; Mark Loeb; George A. Kuchel; Laura Haynes; Janet E. McElhaney; Chris P. Verschoor

doi:10.1093/OFID/OFAA148

Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination

Nathalie Loeb, Melissa K. Andrew, Mark Loeb, George A. Kuchel, Laura Haynes, Janet E. McElhaney, Chris P. Verschoor

Medicine

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23 Citas (Scopus)

Resumen

Background. Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods. We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results. Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions. Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.

Idioma original	English
Número de artículo	ofaa148
Publicación	Open Forum Infectious Diseases
Volumen	7
N.º	5
DOI	https://doi.org/10.1093/OFID/OFAA148
Estado	Published - 2020

Nota bibliográfica

Funding Information:
Financial support. This work was funded by the National Institute on Aging, National Institutes of Health (R01 AG048023; to G. A. K., J. E. M., and coinvestigators). J. E. M. is supported by the Health Sciences North Volunteer Association Chair in Healthy Aging and G. A. K. is supported by the Travelers Chair in Geriatrics and Gerontology.

Funding Information:
Potential conflicts of interest. J. E. M. reports grants from US National Institutes of Health, honoraria for participation in advisory boards from Sanofi, travel support from Sanofi, during the conduct of the study; participation in data monitoring board for GSK, from Pfizer, Merck, ResTORbio, and Medicago, and other from VBI and Janssen for clinical trial work, outside the submitted work. M. K. A. reports grants from Sanofi, GSK, and Pfizer, travel support from Sanofi and GSK, and honoraria from Sanofi and Pfizer, outside the submitted work. G. A. K. reports grants from the US National Institutes of Health and honoraria for participation in advisory boards from ResTORbio and Janssen. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.

ASJC Scopus Subject Areas

Oncology
Clinical Neurology

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Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination. / Loeb, Nathalie; Andrew, Melissa K.; Loeb, Mark et al.
En: Open Forum Infectious Diseases, Vol. 7, N.º 5, ofaa148, 2020.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

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title = "Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination",

abstract = "Background. Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods. We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results. Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions. Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.",

author = "Nathalie Loeb and Andrew, {Melissa K.} and Mark Loeb and Kuchel, {George A.} and Laura Haynes and McElhaney, {Janet E.} and Verschoor, {Chris P.}",

note = "Funding Information: Financial support. This work was funded by the National Institute on Aging, National Institutes of Health (R01 AG048023; to G. A. K., J. E. M., and coinvestigators). J. E. M. is supported by the Health Sciences North Volunteer Association Chair in Healthy Aging and G. A. K. is supported by the Travelers Chair in Geriatrics and Gerontology. Funding Information: Potential conflicts of interest. J. E. M. reports grants from US National Institutes of Health, honoraria for participation in advisory boards from Sanofi, travel support from Sanofi, during the conduct of the study; participation in data monitoring board for GSK, from Pfizer, Merck, ResTORbio, and Medicago, and other from VBI and Janssen for clinical trial work, outside the submitted work. M. K. A. reports grants from Sanofi, GSK, and Pfizer, travel support from Sanofi and GSK, and honoraria from Sanofi and Pfizer, outside the submitted work. G. A. K. reports grants from the US National Institutes of Health and honoraria for participation in advisory boards from ResTORbio and Janssen. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: {\textcopyright} 2020 Oxford University Press. All rights reserved.",

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AU - Andrew, Melissa K.

AU - Loeb, Mark

AU - Kuchel, George A.

AU - Haynes, Laura

AU - McElhaney, Janet E.

AU - Verschoor, Chris P.

N1 - Funding Information: Financial support. This work was funded by the National Institute on Aging, National Institutes of Health (R01 AG048023; to G. A. K., J. E. M., and coinvestigators). J. E. M. is supported by the Health Sciences North Volunteer Association Chair in Healthy Aging and G. A. K. is supported by the Travelers Chair in Geriatrics and Gerontology. Funding Information: Potential conflicts of interest. J. E. M. reports grants from US National Institutes of Health, honoraria for participation in advisory boards from Sanofi, travel support from Sanofi, during the conduct of the study; participation in data monitoring board for GSK, from Pfizer, Merck, ResTORbio, and Medicago, and other from VBI and Janssen for clinical trial work, outside the submitted work. M. K. A. reports grants from Sanofi, GSK, and Pfizer, travel support from Sanofi and GSK, and honoraria from Sanofi and Pfizer, outside the submitted work. G. A. K. reports grants from the US National Institutes of Health and honoraria for participation in advisory boards from ResTORbio and Janssen. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Publisher Copyright: © 2020 Oxford University Press. All rights reserved.

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N2 - Background. Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods. We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results. Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions. Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.

AB - Background. Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses. Methods. We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index. Results. Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients. Conclusions. Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.

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Frailty is associated with increased hemagglutination- inhibition titers in a 4-year randomized trial comparing standard- And high-dose influenza vaccination

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