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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Vydané v:The Journal of infectious diseases Ročník 224; číslo 8; s. 1372
Hlavní autori: 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:English
Vydavateľské údaje: United States 28.10.2021
Predmet:
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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Shrnutí: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.
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ISSN:1537-6613
1537-6613
DOI:10.1093/infdis/jiab111