Aaron L. Oom, Kesi K. Wilson, Stephanie Rettig, Michael Tuen, Marie I. Samanovic, Angelica C. Kottkamp, Ramin S. Herati, Ralf Duerr, Mark J. Mulligan, On behalf of the NYC OSMI Study Group, Abdul Abdulai, Robert Arciuolo, Jaqueline Callahan, Ellie Carmody, Tamia Davis, Amanda Dontino, Aimee Edwin, Celia Engelson, Andrew Fleming, Olivia Frank, Emily Geesey, Shelby Goins, Victoria Guerra, Erika Guevarra, Sarah Haiken, Aaliyah Henry, Kathryn Jano, Trishala Karmacharya, Dorothy Knutsen, Irma Noriega, Maria Null, Samuel Nweke, Lalitha Parameswaran, Robert Pitts, Gurchetan Randhawa, Miguel Rodriguez, Pamela Suman, Apoorva Talanki, Meron Tasissa, Kathryn Swindell, Julia Wagner, Jimmy P. Wilson, Samantha Yip, Miilani Yonatan, Heekoung Youn, L Zhao
The 2022 global outbreak of clade IIb mpox represented a turning point in public health's handling of poxviruses. The primary vaccine available for the prevention of mpox is modified vaccinia Ankara from Bavarian-Nordic (MVA-BN). We previously reported a nondurable and low-avidity antibody response against mpox elicited by MVA-BN. In this study, we expanded upon this knowledge by employing a microneutralization assay to measure monkeypox virus (MPXV) neutralizing titers and a multiplexed immunoassay to assess IgG titers and avidity against eight MPXV antigens and two vaccinia antigens. Through a machine learning analysis, we uncovered that MVA-BN vaccinees without prior smallpox vaccination largely return to a baseline seroprofile within a year of immunization. Notably, we identified a discrete population within this group that mounted a robust neutralizing antibody response associated with a longer dosing interval during the MVA-BN primary series. Furthermore, we found that boosting with a third dose of MVA-BN increases IgG avidity against certain MPXV antigens, as part of a booster-specific seroprofile. These findings provide critical insights into optimizing immune responses through MVA-BN boosters, presenting a potential approach to addressing the limited MPXV-specific immunity observed following the primary series.