Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine

Innocent N. Mbawuike; Robert L. Atmar; Shital M. Patel; David B. Corry; Patricia L. Winokur; Rebecca C. Brady; Wilbur H. Chen; Kathryn M. Edwards; C. Buddy Creech; Emmanuel B. Walter; Sharon E. Frey; Robert B. Belshe; Johannes B. Goll; Heather Hill; Wendy A. Keitel

doi:10.1016/j.vaccine.2015.11.055

Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine

Innocent N. Mbawuike, Robert L. Atmar, Shital M. Patel, David B. Corry, Patricia L. Winokur, Rebecca C. Brady, Wilbur H. Chen, Kathryn M. Edwards, C. Buddy Creech, Emmanuel B. Walter, Sharon E. Frey, Robert B. Belshe, Johannes B. Goll, Heather Hill, Wendy A. Keitel

Research output: Contribution to journal › Article › peer-review

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Abstract

Purpose: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses. Methods: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus. Results: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results. Conclusion: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine.

Original language	English (US)
Pages (from-to)	547-554
Number of pages	8
Journal	Vaccine
Volume	34
Issue number	4
DOIs	https://doi.org/10.1016/j.vaccine.2015.11.055
State	Published - Jan 20 2016

Keywords

Adjuvant
Cell mediated immune response
Cytokine
H5N1
Inactivated influenza vaccine

ASJC Scopus subject areas

Molecular Medicine
Immunology and Microbiology(all)
veterinary(all)
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2015.11.055

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Mbawuike, I. N., Atmar, R. L., Patel, S. M., Corry, D. B., Winokur, P. L., Brady, R. C., Chen, W. H., Edwards, K. M., Creech, C. B., Walter, E. B., Frey, S. E., Belshe, R. B., Goll, J. B., Hill, H., & Keitel, W. A. (2016). Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine. Vaccine, 34(4), 547-554. https://doi.org/10.1016/j.vaccine.2015.11.055

@article{b8f692d7970f4a98a72ea6c155c51ae3,

title = "Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine",

abstract = "Purpose: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses. Methods: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus. Results: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results. Conclusion: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine.",

keywords = "Adjuvant, Cell mediated immune response, Cytokine, H5N1, Inactivated influenza vaccine",

author = "Mbawuike, {Innocent N.} and Atmar, {Robert L.} and Patel, {Shital M.} and Corry, {David B.} and Winokur, {Patricia L.} and Brady, {Rebecca C.} and Chen, {Wilbur H.} and Edwards, {Kathryn M.} and Creech, {C. Buddy} and Walter, {Emmanuel B.} and Frey, {Sharon E.} and Belshe, {Robert B.} and Goll, {Johannes B.} and Heather Hill and Keitel, {Wendy A.}",

note = "Funding Information: This study was funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services as part of the Vaccine and Treatment Evaluation Unit Program ( Baylor College of Medicine , HHSN272200800002C , University of Iowa , HHSN272200800008C , Cincinnati Children's Hospital , HHSN272200800006C , University of Maryland , HHSN272200800001C , Vanderbilt University , HHSN272200800007C , Saint Louis University , HHSN272200800003C , EMMES Corporation , HHSN272200800013C ). Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",

year = "2016",

month = jan,

day = "20",

doi = "10.1016/j.vaccine.2015.11.055",

language = "English (US)",

volume = "34",

pages = "547--554",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier BV",

number = "4",

}

TY - JOUR

T1 - Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine

AU - Mbawuike, Innocent N.

AU - Atmar, Robert L.

AU - Patel, Shital M.

AU - Corry, David B.

AU - Winokur, Patricia L.

AU - Brady, Rebecca C.

AU - Chen, Wilbur H.

AU - Edwards, Kathryn M.

AU - Creech, C. Buddy

AU - Walter, Emmanuel B.

AU - Frey, Sharon E.

AU - Belshe, Robert B.

AU - Goll, Johannes B.

AU - Hill, Heather

AU - Keitel, Wendy A.

N1 - Funding Information: This study was funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services as part of the Vaccine and Treatment Evaluation Unit Program ( Baylor College of Medicine , HHSN272200800002C , University of Iowa , HHSN272200800008C , Cincinnati Children's Hospital , HHSN272200800006C , University of Maryland , HHSN272200800001C , Vanderbilt University , HHSN272200800007C , Saint Louis University , HHSN272200800003C , EMMES Corporation , HHSN272200800013C ). Publisher Copyright: © 2015 Elsevier Ltd. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.

PY - 2016/1/20

Y1 - 2016/1/20

N2 - Purpose: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses. Methods: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus. Results: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results. Conclusion: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine.

AB - Purpose: The study aims were to determine whether inactivated influenza A/H5N1 vaccine administration elicited cell mediated immune (CMI) responses and the impact of adjuvant, vaccine dose and subject age on these responses. Methods: Adults who were previously primed with either adjuvanted or unadjuvanted, inactivated, A/H5N1/Vietnam/1203/2004 (Clade 1) vaccine or unprimed (received placebo) in previous vaccine studies were randomized to receive one (primed) or two (unprimed) 15- or 90-mcg doses of inactivated, A/H5N1/Indonesia/05/05 (Clade 2) vaccine. Peripheral blood mononuclear cells (PBMCs) were collected and analyzed from a subset of vaccinees to assess CMI responses using IFN-γ and granzyme B ELISPOT assays. Cytokine measurements were performed on PBMC supernatants after stimulation with H5N1 virus. Results: PBMCs were available from 177 participants; 88 and 89 received 15-mcg and 90-mcg of unadjuvanted clade 2 vaccine, respectively. Following H5N1 clade 1 stimulation, IFN-γ but not granzyme B normalized spot-forming cell numbers had statistically significant increased numbers at each of the post-vaccination timepoints compared to baseline in pooled analyses of all vaccine doses and age groups. Clade 2 stimulation resulted in statistically significant increased numbers of IFN-γ cells only 180 days following the last vaccination. Responses were similar among younger and older study participants, as were responses among those primed with alum-adjuvanted or non-adjuvanted clade 1 H5N1 vaccines. The dosage of clade 2 vaccine did not impact CMI responses among primed subjects, but responses were statistically significantly greater in unprimed recipients of the 90-mcg dosage compared to unprimed recipients of the 15-mcg dosage. IFN-γ levels in the supernatants of stimulated PBMC were strongly correlated with IFN-γ ELISPOT results. Conclusion: CMI responses occur in adults administered influenza A/H5N1 inactivated influenza vaccine.

KW - Adjuvant

KW - Cell mediated immune response

KW - Cytokine

KW - H5N1

KW - Inactivated influenza vaccine

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DO - 10.1016/j.vaccine.2015.11.055

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AN - SCOPUS:84952939502

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SP - 547

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JO - Vaccine

JF - Vaccine

SN - 0264-410X

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ER -

Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine

Abstract

Keywords

ASJC Scopus subject areas

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