Document resource
Background The third-generation smallpox vaccine, MVA-BN, is now considered the primary preventive measure against mpox infection. A booster dose administered at least two years after the primary vaccination significantly enhances both humoral and cellular responses. Assessing whether the subcutaneous (SC) or intradermal (ID) administration route influences the magnitude of the response may inform public health strategies for maximising dose savings.Methods A prospective observational study was conducted in individuals who had completed a two-dose primary MVA-BN vaccination cycle and received a booster dose either subcutaneously (SC, 0.5 mL) or intradermally (ID, 0.1 mL), at least 2 years after. Blood samples were collected at the time of booster administration (T1), after 4 weeks (T2), and 8 weeks (T3). Anti-MPXV IgG titers were measured by immunofluorescence assay (IFA, clade IIb), neutralizing antibodies (nAb) by PRNT50 (clade IIb), and MVA-BN-responsive T-cells by ELISpot. Clinical and immunological features were compared between SC and ID groups using the Mann-Whitney tests.Results Among the 60 participants included, 34 (56.7%) received SC and 26 (43.3%) ID. Fifty-nine (98.3%) were males, with a median age of 43.3 years [IQR 36.7–50.0]; 6 of them (10.0%) were people with HIV (PWH) ( table 1). From T1 to T3, IgG titers increased significantly in both SC and ID groups (p < 0.001). Reactive sera increased from 47% to 100% in SC and 60% to 100% in ID. No difference in IgG titer increase was found between groups (figure 1A). Additionally, nAb titers significantly increased from T1 to T3 (p < 0.0001), with reactivity ranging from 6% to 89% for SC; as far as ID is concerned, the percentage of reactivity ranged from 23% at T1, to 91% at T2 and to 82% at T3. Comparison between groups showed a significant advantage for ID over SC in the increase of nAb titers both at T1 (p=0.634) and T2 (p = 0.0017), while at T3 the differences between groups were not significant (p=0386) (figure 1B). MVA-specific T-cell response also improved from baseline to one month after administration in both the SC (p<0.0001) and ID (p<0.002) groups. No evidence of a difference in response variation between the two groups was found (data not shown).Conclusions Both subcutaneous and intradermal routes of administration of the MVA-BN booster dose elicit strong humoral and cellular responses, with a transient advantage for the intradermal route in improving the neutralizing response within the first 4 weeks following administration. These results support the use of the intradermal route for booster administration to conserve vaccine resources and optimise the possibilities for intervention in high-risk populations.Abstract SC16 Figure 1Kinetics of MPXV-specific IgG (A) and neutralising antibodies (nAbs) (B) the time of booster administration (T1), after 4 weeks (T2) and after 8 weeks. Dot lines represent the detection limit for IgG (1:20), nAbs (1:10). Geometric mean IgG and nAbs titers (GMT-95% CI) are shown for each time range or study groupAbstract SC16 Table 1General characteristics