Moraes-Cardoso I, Benet S, Carabelli J, Perez-Zsolt D, Mendoza A, Rivero A, Alemany A, Descalzo V, Alarcón-Soto Y, Grifoni A, Sette A, Moltó J, Marc A, Marks M, Mitjà O, Brander C, Paredes R, Izquierdo-Useros N, Carrillo J, Suñer C, Olvera A, and Mothe B
Background: Since the emergence of the global mpox outbreak in May, 2022, more than 90 000 cases have been diagnosed across 110 countries, disproportionately affecting people with HIV. The durability of mpox-specific immunity is unclear and reinfections have been reported. We aimed to compare mpox immune responses up to 6 months after diagnosis in participants with and without HIV and assess their effect on disease severity and viral clearance dynamics., Methods: This study was embedded within a prospective, observational, multicentre cohort study of viral clearance dynamics among people with mpox in Spain (MoViE). We included women and men aged 18 years or older, who had signs of mpox, and reported having symptom onset within the previous 10 days at the moment of mpox diagnosis from three sex clinics of the Barcelona metropolitan area. Samples from skin ulcers were collected weekly to estimate the time to clear monkeypox virus (MPXV) from skin lesions. Blood samples were taken at diagnosis, 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralisation, and characterising mpox-specific T-cell responses using interferon γ detecting enzyme-linked immunospot (ELISpot) assay and multiparametric flow cytometry., Findings: Of the 77 originally enrolled participants, we included 33 participants recruited between July 19, and Oct 6, 2022. Participants without HIV (19 [58%] participants) and participants with HIV (14 [42%] participants) had similar clinical severity and time to MPXV clearance in skin lesions. Participants with HIV had a CD4 + T-cell count median of 777 cells per μL (IQR 484-1533), and 11 (78%) of 14 were virally suppressed on antiretroviral therapy. Nine (27%) of 33 participants were age 49 years or older. 15 (45%) of 33 participants were originally from Spain, and all participants were men. Early humoral responses, particularly concentrations and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Orthopoxvirus-specific T cells count was also positively correlated with MPXV clearance. Antibody titres declined more rapidly in participants with HIV, but T-cell responses against MPXV were sustained up to day 182 after diagnosis, regardless of HIV status., Interpretation: Higher breadth and magnitude of B-cell and T-cell responses are important in facilitating local viral clearance, limiting mpox dissemination, and reducing disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control and T-cell responses are sustained over time, which might contribute to milder presentations during reinfection., Funding: Fundació Lluita contra les Infeccions, IrsiCaixa, and Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación e Universidades., Competing Interests: Declaration of interests BM reports consultancy personal fees from AELIX Therapeutics and AbbViE and speaker fees from Gilead, Janssen, and ViiV Healthcare. AG is a consultant for Pfizer, outside the submitted work. CB is cofounder, CSO, and shareholder of AELIX Therapeutics and reports consultancy personal fees from Omniscope, Virometix, and Astrivax. AS is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Darwin Health, EmerVax, EUROIMMUN, F Hoffman-La Roche, Fortress Biotech, Gilead Sciences, Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. NI-U reports funding support from the Spanish Ministry of Science and Innovation, HIPRA, Pharma Mar, Amassence, Mynorix, Grifols, and SME. RP reports financial fundings from MSD, ViiV Healthcare, Gilead Sciences, and PharmaMar, and consulting fees or honoraria from Gilead Sciences, Pfizer, AstraZeneca, Roche therapeutics, MSD, GSK ViiV Healthcare, Eli Lilly and Company, PharmaMar, and Atea Pharmaceutics. JM reports consulting fees, honoraria, expert testimony payment, and financial support from ViiV Healthcare, Johnson & Jonhson, Gilead, and MSD. La Jolla Institute has filed for patent protection for various aspects of T-cell epitope and vaccine design work. The authors declare no other competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)