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The modified vaccinia Ankara–Bavarian Nordic (MVA-BN; Jynneos) vaccine was recommended by the Centers for Disease Control and Prevention for mpox infection during the 2022 clade IIb mpox outbreak. Because of limited supply, the recommended MVA-BN administration was modified from 0.5 mL given subcutaneously to 0.1 mL given intradermally,¹ which were comparably immunogenic.^2,3 On August 14, 2024, the World Health Organization declared the mpox clade Ib outbreak in the Democratic Republic of the Congo a public health emergency of international concern.⁴ It is therefore important to assess the durability of vaccine immunity and reinfection risk⁵ for people who were vaccinated with MVA-BN in 2022. Two doses of MVA-BN are recommended, although some individuals received only 1 dose. Two doses provided 66% effectiveness and 1 dose provided 36% effectiveness at peak immunity during the 2022 mpox outbreak.² We assessed mpox-specific immune responses for 12 months after MVA-BN vaccination.

We used serum specimens from a biorepository at Beth Israel Deaconess Medical Center (BIDMC) from a convenience sample of adults who received the MVA-BN vaccine or had confirmed diagnosis of mpox infection during the 2022 outbreak. The study was performed between August 24, 2022, and October 13, 2023. We assessed serum antibody and T-cell responses after 2-dose or 1-dose MVA-BN vaccination delivered subcutaneously or intradermally. Binding antibody responses to mpox antigens M1R, B6R, A35R, A29L, and H3L, which correlate with protection in nonhuman primates,³ were assessed at baseline, 3 weeks (peak immunity), 3 months, 6 months, 9 months, and 12 months. Mpox neutralizing antibody responses were measured at baseline, 3 months, and 9 months; T-cell responses to vaccinia-infected autologous target cells, at 9 months. Antibody levels that correlate with protection in humans are not defined. The eAppendix in Supplement 1 provides assay details. Antibody titers are presented with medians without formal statistical analysis. The BIDMC institutional review board approved this study. All participants provided oral informed consent.

We recruited 45 adults who received 2 doses (n = 22) or 1 dose (n = 26) of the MVA-BN vaccine or had confirmed diagnosis of mpox infection (n = 3) (median age, 25 years [range, 20-66 years]; 53% were female) (Table). In participants who received 2 doses of the MVA-BN vaccine, median binding antibody enzyme-linked immunosorbent assay (ELISA) titers to mpox M1R, B6R, A35R, A29L, and H3L antigens were 28, 25, 25, 27, and 27 at baseline, respectively, and peaked at 112, 384, 85, 29, and 76 at week 3 after vaccination but then declined to 38, 82, 32, 25, and 31 at 12 months (Figure, A). In participants who received 1 dose of MVA-BN, the median binding antibody ELISA titers to mpox M1R, B6R, A35R, A29L, and H3L antigens peaked at 45, 90, 32, 31, and 28 at week 3 but then declined to 33, 43, 30, 25, and 28 at 12 months (Figure, B). Mpox serum neutralizing antibody titers were minimal in participants after 2-dose or 1-dose MVA-BN vaccines (median titers, 11 and 9.5, respectively) at 3 months. High titers of mpox neutralizing antibodies (median titer, 965) were detected at 3 months after natural infection and persisted at 9 months postinfection (median titer, 284; Figure, C). Low interferon gamma CD4⁺ and CD8⁺ T-cell responses were detected to vaccinia-infected target cells by intracellular cytokine staining assays at 9 months after 2-dose and 1-dose MVA-BN vaccination (median CD4⁺ responses, 0.024% and 0.016%; median CD8⁺ responses, 0.053% and 0.013%, respectively).

MVA-BN vaccination generated mpox antibodies that waned by 6 to 12 months. In participants who received 2 doses of MVA-BN vaccine, mpox antibody responses at 12 months were comparable to or lower than peak antibody responses in people receiving 1 dose, which provided limited protection.² Serum antibody titers after vaccination have been shown to correlate with protection against mpox challenge in nonhuman primates.^3,6 Moreover, a cluster of mpox infections was reported in 2023 in vaccinated humans with waning immunity.⁵ These data suggest that protective immunity may be waning in individuals who were vaccinated with MVA-BN in 2022 and that boosting may be required to maintain robust levels of protective immunity. Study limitations include its small sample size, convenience sample, and observational design. Larger studies are needed to confirm generalizability and to assess vaccine effectiveness over time.

Accepted for Publication: September 20, 2024.

Published Online: October 3, 2024. doi:10.1001/jama.2024.20951

Corresponding Author: Dan H. Barouch, MD, PhD, Center for Virology and Vaccine Research, 330 Brookline Ave, E/CLS-1043, Boston, MA 02115 (dbarouch@bidmc.harvard.edu).

Author Contributions: Drs Collier and Barouch had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Collier, Barouch.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Collier, Barouch.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Collier, Liu.

Obtained funding: Barouch.

Administrative, technical, or material support: All authors.

Supervision: Collier, McMahan, Barouch.

Conflict of Interest Disclosures: Dr Collier reported grants from the Massachusetts Consortium on Pathogen Readiness (MassCPR) during the conduct of the study. Dr Barouch reported grants from the Biomedical Advanced Research and Development Authority, Defense Advanced Research Projects Agency, Bill & Melinda Gates Foundation, Henry M. Jackson Foundation, MassCPR, National Cancer Institute, National Institute of Allergy and Infectious Diseases (NIAID), Ragon Institute, South African Medical Research Council, Walter Reed Army Institute of Research, Alkermes, CureVac, Gilead, Gritstone, GSK, Hookipa, Intima, Janssen, Legend, Leyden Labs, Musk Foundation, Novavax, Pfizer, Pharm-Olam, Sanofi, and Zentalis; equity in Celsion/Imunon; and consulting fees from Avidea, Celsion/Imunon, Laronde, Meissa, SQZ, and Sterne Kessler; and is the founder of and has equity in Vector Sciences outside the submitted work. No other disclosures were reported.

Funding/Support: The authors acknowledge National Institutes of Health grant CA260476, support from MassCPR (Dr Barouch), and support from NIAID Division of Intramural Research (Dr Moss).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2.

Additional Contributions: We thank Lydia Gallup, MSN, RN, Siline Thai, BS, Eleanor Schonberg, BS, and Marjorie Rowe, BS, for participant recruitment; and Tochi Anioke, BS, Amelia Hoyt, BS, Orion Barnett, BS, Juliana Pereira, BS, Audrey Mutoni, BS, Bridget Wixted, BS, Krishna Shah, MS, Bismark Acquah, MS, Kristin Gotthardt, BS, Reed Boduch, BS, Michelle A. Lifton, BS, MT, Maxinne Ignacio, BS, and Catherine Cotter, MS, for technical assistance. All individuals are affiliated with BIDMC, except Ms Ignacio and Ms Cotter, who are affiliated with NIAID. None of these individuals received compensation for their contributions.