AI Article Synopsis

  • The study investigates the immunological responses to the modified vaccinia Ankara (MVA) smallpox vaccine using 523 participants who received either lyophilized or liquid MVA in different administration methods.
  • Results showed that MVA triggered significant antibody production against several viral proteins, particularly after 28 and 42 days, with strong correlations between some antibody responses and plaque reduction neutralization tests (PRNT).
  • The findings suggest that specific proteins from the MVA vaccine could be potential indicators of protection and may inform future vaccine development strategies.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861366PMC
http://dx.doi.org/10.1093/infdis/jiab111DOI Listing

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