Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals
Mathieu Hubert
(1)
,
Florence Guivel-Benhassine
(1)
,
Timothée Bruel
(1, 2)
,
Françoise Porrot
(1)
,
Delphine Planas
(1, 2)
,
Jessica Vanhomwegen
(3)
,
Aurélie Wiedemann
(2, 4)
,
Sonia Burrel
(5)
,
Stéphane Marot
(6, 7)
,
Romain Palich
(6, 7)
,
Gentiane Monsel
(6, 7)
,
Harouna Diombera
(2, 4)
,
Sébastien Gallien
(8)
,
Jose Luis Lopez-Zaragoza
(8)
,
William Vindrios
(8)
,
Fabien Taieb
(9)
,
Sandrine Fernandes-Pellerin
(10)
,
Maurine Delhaye
(10)
,
Hélène Laude
(10)
,
Laurence Arowas
(10)
,
Marie-Noelle Ungeheuer
(10)
,
Laurent Hocqueloux
(11)
,
Valérie Pourcher
(6, 7)
,
Thierry Prazuck
(11)
,
Anne-Geneviève Marcelin
(6, 7)
,
Jean-Daniel Lelièvre
(2, 4, 8)
,
Christophe Batéjat
(3)
,
Yves Lévy
(2, 4, 8)
,
Jean-Claude Manuguerra
(3)
,
Olivier Schwartz
(1, 2)
1
CNRS-UMR3569 -
Virus et Immunité - Virus and immunity
2 VRI - Vaccine Research Institute [Créteil, France]
3 ERI - Environnement et Risques infectieux - Environment and Infectious Risks
4 IMRB - Institut Mondor de Recherche Biomédicale
5 MFP - Microbiologie Fondamentale et Pathogénicité
6 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
7 CHU Charles Foix [AP-HP]
8 Groupe Henri Mondor-Albert Chenevier
9 CMIP - Centre Médical de l'Institut Pasteur
10 ICAReB-Clin - Plate-forme d’Investigation Clinique / Clinical Investigation Platform
11 CHRO - Centre Hospitalier Régional d'Orléans
2 VRI - Vaccine Research Institute [Créteil, France]
3 ERI - Environnement et Risques infectieux - Environment and Infectious Risks
4 IMRB - Institut Mondor de Recherche Biomédicale
5 MFP - Microbiologie Fondamentale et Pathogénicité
6 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
7 CHU Charles Foix [AP-HP]
8 Groupe Henri Mondor-Albert Chenevier
9 CMIP - Centre Médical de l'Institut Pasteur
10 ICAReB-Clin - Plate-forme d’Investigation Clinique / Clinical Investigation Platform
11 CHRO - Centre Hospitalier Régional d'Orléans
Timothée Bruel
- Fonction : Auteur
- PersonId : 746191
- IdHAL : timothee-bruel
- ORCID : 0000-0002-3952-4261
- IdRef : 169340171
Jessica Vanhomwegen
- Fonction : Auteur
- PersonId : 735109
- IdHAL : jessica-vanhomwegen
- ORCID : 0000-0002-7879-1485
- IdRef : 181029960
Sébastien Gallien
- Fonction : Auteur
- PersonId : 760825
- IdHAL : sebastien-gallien
- ORCID : 0000-0002-8033-0936
Jean-Claude Manuguerra
- Fonction : Auteur
- PersonId : 920746
- IdHAL : jean-claude-manuguerra
- ORCID : 0000-0002-5202-6531
- IdRef : 050363506
Olivier Schwartz
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 757442
- ORCID : 0000-0002-0729-1475
- IdRef : 128673850
Connectez-vous pour contacter l'auteur
Résumé
Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.