Immune Responses Associated with Mpox Viral Clearance in a Prospective Observational Cohort of People with and Without HIV in Spain

Abstract

Background: Since the emergence of the global mpox outbreak in May 2022, over 90,000 cases have been diagnosed across 110 countries, disproportionately affecting those living with HIV. Unlike previous outbreaks, the primary presentation has featured more prominent anogenital and/or oropharyngeal/perioral ulcers and fewer systemic symptoms. The durability of mpox-specific immunity is unclear and re-infections have been reported. We aimed to compare mpox immune responses in people without HIV (PWoH) and with HIV (PWH), determine their impact on disease severity and viral clearance dynamics, and assess the durability of post-infection immunity.

Methods: The study was nested in a cohort of mpox conducted in Spain (NCT054476744). Samples from skin ulcers were collected weekly to estimate the time to clear mpox virus (MPXV) from skin lesions. Blood samples were taken at mpox diagnosis and 29, 91, and 182 days later for immune analysis. This included quantifying IgG and IgA against three mpox antigens by ELISA, evaluating in-vitro neutralization, and characterizing mpox-specific T-cell responses using IFNγ ELISpot and multiparametric flow cytometry.

Findings: PWoH and PWH had similar clinical severity and time to MPXV clearance in skin lesions. Early humoral responses, particularly levels and breadth of IgG and IgA, were associated with milder disease and faster viral clearance. Antibody titers declined more rapidly in PWH, but cellular responses against mpox were sustained up to 6 months after infection, regardless of HIV status.

Interpretation: Strong and broad humoral and cellular immune responses are important in facilitating local viral clearance and thus, limiting mpox dissemination and disease severity in individuals with preserved immune system. Antibodies appear to contribute to early viral control, while cellular responses are sustained over time, what might contribute to milder presentations upon reinfection.

Trial Registration: NCT054476744.

Funding: Fight Infections Foundation, IrsiCaixa AIDS Research Institute and CIBERINFEC (ISCIII).

Declaration of Interest: B.M. reports consultancy personal fees from AELIX Therapeutics SL and AbbviE, as well as speakers’ fees from Gilead, Janssen and ViiV Healthcare, outside the submitted work. A.G. is a consultant for Pfizer. C.B. is co-founder, CSO and shareholder of AELIX Therapeutics SL and reports consultancy personal fees from Omniscope, Virometix and Astrivax. A.S. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. LJI has filed for patent protection for various aspects of T-cell epitope and vaccine design work. The authors declare no other related competing interest.

Ethical Approval: The study protocol was approved by the Ethics Committee of the Hospital Germans Trias i Pujol (PI-22-156), and written informed consent was obtained from all participants before enrolment.

Keywords: monkeypox, monkeypox virus, MPXV, mpox, natural immunity, mpox antibodies, mpox T-cells, mpox viral clearance, mpox severity, PWH, HIV