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Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses
- Source :
- J Infect Dis
- Publication Year :
- 2020
-
Abstract
- Background There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. Methods 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. 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. Conclusions 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. Clinical Trials Registration NCT00914732.
- Subjects :
- 0301 basic medicine
Modified vaccinia Ankara
viruses
Protein Array Analysis
Vaccinia virus
Vaccines, Attenuated
complex mixtures
03 medical and health sciences
chemistry.chemical_compound
Major Articles and Brief Reports
0302 clinical medicine
Antigen
Vaccines, DNA
Vaccinia
Immunology and Allergy
Humans
030212 general & internal medicine
Antigens, Viral
Antibody-dependent cell-mediated cytotoxicity
Immunity, Cellular
biology
ELISPOT
Virion membrane
Antibody-Dependent Cell Cytotoxicity
hemic and immune systems
Viral Vaccines
Titer
030104 developmental biology
Infectious Diseases
chemistry
Immunology
Antibody Formation
biology.protein
Immunization
Antibody
Smallpox Vaccine
Subjects
Details
- ISSN :
- 15376613
- Volume :
- 224
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- The Journal of infectious diseases
- Accession number :
- edsair.doi.dedup.....6d3fbf5f07bc85af4d8aec5a004f06c2