MVA-EL(The Chinese University of Hong Kong)

To expand the supply of the modified vaccinia Ankara (MVA) smallpox/mpox vaccine, fractional doses administered intradermally (ID) have been considered as alternatives to the standard dose given subcutaneously (SC). In a recent clinical trial, participants received the standard 10⁸ infectious units of vaccine SC or a one-fifth (IDH) or a one-tenth (IDL) dose ID twice 28-days apart. Two weeks after the second dose, sera were analyzed using a vaccinia virus (VACV) strain Western Reserve plaque-reduction test (PRNT) with the conclusion that IDH but not IDL was non-inferior to SC. The present study extends the latter by quantifying neutralizing antibodies to the MVA vaccine and to monkeypox virus (MPXV) in the absence and presence of added complement and by assessing multiplex binding antibodies to individual VACV antigens (A27, A33, B5, D8 and L1) and the MPXV homologs (A29, A35, B6, E8 and M1). The main conclusions of the study are that the titers of MVA neutralizing antibodies induced by SC and IDH were not significantly different, whereas MVA neutralizing antibody titers induced by IDL were lower like the previous PRNT results. However, the titers of complement-enhanced MPXV neutralizing antibodies induced by SC were significantly higher than for both IDH and IDL immunizations, suggesting that the standard SC dose and reduced dose ID immunizations may not be equivalent. Additional analyses suggested that antibody binding to VACV B5 and D8 and MPXV B6 and E8 may serve as surrogates for neutralizing antibodies.