Immunogenicity and reactogenicity of modified vaccinia Ankara pre-exposure vaccination against mpox according to previous smallpox vaccine exposure and HIV infection: prospective cohort study.
Autor: | Mazzotta V; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.; PhD Course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome Tor Vergata, Rome, Italy., Lepri AC; Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, UK., Matusali G; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Cimini E; Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy., Piselli P; Clinical Epidemiology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Aguglia C; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.; Infectious Diseases Unit, Tor Vergata University Hospital, Rome, Italy., Lanini S; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Colavita F; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.; PhD Course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome Tor Vergata, Rome, Italy., Notari S; Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy., Oliva A; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Meschi S; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Casetti R; Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy., Mondillo V; Health Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Vergori A; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.; PhD Course in Microbiology, Immunology, Infectious Diseases, and Transplants (MIMIT), University of Rome Tor Vergata, Rome, Italy., Bettini A; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Grassi G; Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy., Pinnetti C; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Lapa D; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Tartaglia E; Cellular Immunology and Pharmacology Laboratory, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy., Gallì P; Health Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Mondi A; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Montagnari G; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy.; Infectious Diseases Unit, Tor Vergata University Hospital, Rome, Italy., Gagliardini R; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Nicastri E; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Lichtner M; Infectious Diseases Unit, Santa Maria Goretti Hospital of Latina, NESMOS Department, Sapienza University of Rome, Italy., Sarmati L; Infectious Diseases Unit, Tor Vergata University Hospital, Rome, Italy., Tamburrini E; Department of Safety and Bioethics, Catholic University of the Sacred Heart, Rome, Italy.; Infectious Diseases Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Mastroianni C; Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy., Stingone C; STI/HIV Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy., Siddu A; General Directorate of Prevention, Ministry of Health, Rome, Italy., Barca A; Unit of Health Promotion and Prevention, Directorate of Health and Integration, Lazio Region, Rome, Italy., Fontana C; Laboratory of Microbiology and Biological Bank Unit, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Agrati C; Department of Onco-Haematology, and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Girardi E; Scientific Direction, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Vaia F; General Directorate of Prevention, Ministry of Health, Rome, Italy., Maggi F; Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy., Antinori A; Clinical Infectious Diseases Department, National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy. |
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Jazyk: | angličtina |
Zdroj: | EClinicalMedicine [EClinicalMedicine] 2024 Jan 12; Vol. 68, pp. 102420. Date of Electronic Publication: 2024 Jan 12 (Print Publication: 2024). |
DOI: | 10.1016/j.eclinm.2023.102420 |
Abstrakt: | 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: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log 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: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS "Advanced grant 5 × 1000, 2021" and by the Italian Ministry of Health " Ricerca Corrente Linea 2 ". Competing Interests: The authors declare that no conflicting financial interests or other competing relationships exist. (© 2023 The Author(s).) |
Databáze: | MEDLINE |
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