Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study
Valentina Mazzotta, Alessandro Cozzi‐Lepri, Giulia Matusali, Eleonora Cimini, Pierluca Piselli, Camilla Aguglia, Simone Lanini, Francesca Colavita, Stefania Notari, Alessandra Oliva, Silvia Meschi, Rita Casetti, Vanessa Mondillo, Alessandra Vergori, Aurora Bettini, Germana Grassi, Carmela Pinnetti, Daniele Lapa, Eleonora Tartaglia, Paola Gallì, Annalisa Mondi, G Montagnari, Roberta Gagliardini, Emanuele Nicastri, Miriam Lichtner, Loredana Sarmati, Enrica Tamburrini, Claudio Maria Mastroianni, Christof Stingone, Andrea Siddu, Alessandra Barca, Carla Fontana, Chiara Agrati, Enrico Girardi, Francesco Vaia, Fabrizio Maggi, Andrea Antinori, E. Anzalone, Marta Camici, Fabio Cannone, Priscilla Caputi, Claudia Cimaglia, Rita Corso, Flavia Cristofanelli, Stefania Cruciani, Nicola de Marco, Chiara De Ponte, Giulia Del Duca, Paolo Faccendini, Francesca Faraglia, Augusto Faticoni, Marisa Fusto, Saba Gebremeskel, Maria Letizia Giancola, Giuseppina Giannico, Simona Gili, Maria Rosaria Iannella, Angela Junea, Alessandra Lamonaca, Alessandra Marani, Erminia Masone, Ilaria Mastrorosa, Stefania Mazzotta, Alessandra Nappo, Giorgia Natalini, A. Parisi, Sara Passacantilli, Jessica Paulicelli, Maria Maddalena Plazzi, Adriano Possi, Gianni Preziosi, Silvia Rosati, Marika Rubino, Pietro Scanzano, Laura Scorzolini, Virginia Tomassi, Maurizio Vescovo, Serena Vita, Luciano Caterini, Luigi Coppola, Dimitra Kontogiannis, Gabriella d’Ettorre, Marco Ridolfi, Simona Di Giambenedetto, Damiano Farinacci, Alessandra Latini, Mauro Marchili, Raffaella Marocco
Abstract
Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: , starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p = 0.037; OR 0.30 (0.10-0.88), p = 0.029 and OR 0.19 (0.05-0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: ".