Human antibody responses following vaccinia immunization using protein microarrays and correlation with cell-mediated and antibody dependent cellular cytotoxicity responses.
BACKGROUND: There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine.
METHODS: Five hundred twenty-three vaccinia-naïve subjects were randomized to receive two vaccine doses, either lyophilized MVA subcutaneously (SC), liquid MVA SC or liquid MVA intradermally (ID) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), IFN- γ release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with PRNT, enzyme-linked immunosorbent assay (ELISA), 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 nine antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three correlated for 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 fifteen vaccinia strain antigens representing virion membrane. Antibody responses to two 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.