Unique Kinetics of the Human Milk Antibody Response to JYNNEOS Vaccine for Prevention of Monkey Pox: A Case Study

<b><i>Background:</i></b> JYNNEOS is a nonreplicating modified vaccinia Ankara vaccine currently licensed to prevent monkeypox infection, and its milk immunogenicity remains unstudied. <b><i>Objective:</i></b> Investigate the human milk immunogenicity of the JYNNEOS vaccine in one individual and examine the milk for evidence of vaccine components. <b><i>Methods:</i></b> Immunogenicity of milk and plasma samples were tested by Luminex assays against Vaccinia antigens, and vaccine components were tested using PCR and sandwich ELISA. <b><i>Results:</i></b> Plasma antibody (Ab) response increased up to 3.7-fold in immunoglobulin G (IgG) titer and 1.4-fold in IgA compared with baseline, confirming vaccine immunogenicity in this participant 2 weeks post dose 2. Specific plasma IgG remained 1.2- to 1.7-fold above baseline 12 weeks post dose 2, while IgA returned to baseline levels. Notably, the milk response exhibited unique kinetics, particularly for IgA. Milk IgA against all three antigens increased 0.9- to 2.2-fold 2 weeks post dose 2, reaching a peak titer increase of 1.1- to 2.7-fold at 12 weeks post dose 2. Secretory (s) Ab levels increased to 1.1- to 2-fold at 2 weeks post dose 2 and reached a peak of 2- to 3.2-fold increase at the 12-week time point. Importantly, IgA and sAb responses in milk exhibited correlation, suggesting most milk IgA was sIgA. Notably, no vaccine components (VACV protein or DNA) were detected in the milk samples. <b><i>Conclusion:</i></b> These data suggest that the milk Ab response to this intradermal (ID) VACV-based vaccine is distinct from that observed systemically, indicating a unique mucosal immune response and highlighting its potential to elicit protective long-lasting sIgA. This case report provides strong evidence for inclusion of this vaccine platform in future studies of maternal vaccines aimed to elicit a protective milk Ab response.