Differences in Mpox and Vaccinia Immunity Induced by Non-Replicating and Replicating Vaccinia-Based Vaccines

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Mpox outbreaks, including clade I and IIb viruses, pose significant public health challenges.
• The non-replicating Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine elicits low and rapidly waning mpox-neutralizing antibody responses.
• Evaluating different vaccine types is crucial for effective mpox control strategies.

Purpose of the Study:

• To compare the mpox-specific immunity induced by a replication-competent smallpox vaccine (Dryvax) versus the non-replicating MVA-BN vaccine.
• To assess both antibody and T cell responses following vaccination with Dryvax and MVA-BN.

Main Methods:

• Utilized stored sera and peripheral blood mononuclear cells (PBMCs) from clinical trials of MVA-BN and Dryvax.
• Quantified mpox-neutralizing antibody titers using the focus reduction neutralization test (FRNT50).
• Measured mpox-specific T cell responses via interferon-gamma (IFN-γ) ELISPOT assay.

Main Results:

• Dryvax recipients exhibited a >10-fold higher peak mpox-neutralizing antibody titer compared to MVA-BN recipients.
• At 180 days post-vaccination, antibody titers in Dryvax recipients were >20 times higher than in MVA-BN recipients.
• MVA-BN vaccination induced similar or higher levels of mpox-specific T cell responses (IFN-γ ELISPOT) compared to Dryvax.

Conclusions:

• Replication-competent smallpox vaccines induce superior and more sustained antibody-mediated immunity against mpox compared to MVA-BN.
• MVA-BN demonstrates comparable or potentially enhanced T cell-mediated immunity.
• Vaccine-induced immune responses differ significantly between replication-competent and non-replicating viral vectors for mpox.