Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses

There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC grou...

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Vydáno v:The Journal of infectious diseases Ročník 224; číslo 8; s. 1372
Hlavní autoři: Frey, Sharon E, Stapleton, Jack T, Ballas, Zuhair K, Rasmussen, Wendy L, Kaufman, Thomas M, Blevins, Tammy P, Jensen, Travis L, Davies, D Huw, Tary-Lehmann, Magdalena, Chaplin, Paul, Hill, Heather, Goll, Johannes B
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 28.10.2021
Témata:
Antibody Formation
Antibody-Dependent Cell Cytotoxicity
Antigens, Viral
Humans
Immunity, Cellular
Immunization
Protein Array Analysis
Smallpox Vaccine - administration & dosage
Vaccines, Attenuated
Vaccines, DNA - administration & dosage
Vaccinia
Vaccinia virus - immunology
Viral Vaccines - administration & dosage
correlation of protection
modified vaccinia Ankara
membrane proteins
protein microarray
vaccinia western reserve
smallpox
ADCC
ELISPOT
antibody responses
MVA vaccine
ISSN:1537-6613, 1537-6613
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Abstract There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. NCT00914732.
AbstractList There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine.BACKGROUNDThere are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine.A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results.METHODSA total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results.MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses.RESULTSMVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses.MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development.CONCLUSIONSMVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development.NCT00914732.CLINICAL TRIALS REGISTRATIONNCT00914732.
There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development. NCT00914732.
Author Goll, Johannes B
Kaufman, Thomas M
Davies, D Huw
Frey, Sharon E
Stapleton, Jack T
Blevins, Tammy P
Tary-Lehmann, Magdalena
Jensen, Travis L
Chaplin, Paul
Hill, Heather
Ballas, Zuhair K
Rasmussen, Wendy L
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Johnston, Christine
Atmar, Robert
Chen, Wilbur H
Keitel, Wendy
El-Kamary, Samer S
Patel, Shital M
Rouphael, Nadine
Edupuganti, Srilatha
Winokur, Patricia
Jackson, Lisa A
El Sahly, Hana
Mulligan, Mark
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Copyright The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Issue 8
Keywords correlation of protection
modified vaccinia Ankara
membrane proteins
protein microarray
vaccinia western reserve
smallpox
ADCC
ELISPOT
antibody responses
MVA vaccine
Language English
License The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Snippet There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. A total of 523 vaccinia-naive...
There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine.BACKGROUNDThere are limited...
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SubjectTerms Antibody Formation
Antibody-Dependent Cell Cytotoxicity
Antigens, Viral
Humans
Immunity, Cellular
Immunization
Protein Array Analysis
Smallpox Vaccine - administration & dosage
Vaccines, Attenuated
Vaccines, DNA - administration & dosage
Vaccinia
Vaccinia virus - immunology
Viral Vaccines - administration & dosage
Title Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses
URI https://www.ncbi.nlm.nih.gov/pubmed/33675226
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