SARS-CoV-2 vaccination elicits unconventional IgM specific responses in naïve and previously COVID-19-infected individuals
Alessandra Ruggiero,
Chiara Piubelli,
Lucia Calciano,
Simone Accordini,
Maria Teresa Valenti,
Luca Dalle Carbonare,
Gabriel Siracusano,
Nigel Temperton,
Natalia Tiberti,
Silvia Stefania Longoni,
Massimo Pizzato,
Silvia Accordini,
Tobia Fantoni,
Lucia Lopalco,
Alberto Beretta,
Zeno Bisoffi,
Donato Zipeto
Affiliations
Alessandra Ruggiero
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Chiara Piubelli
Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (VR), Italy
Lucia Calciano
Department of Diagnostics and Public Health, University of Verona, Verona, Italy
Simone Accordini
Department of Diagnostics and Public Health, University of Verona, Verona, Italy
Maria Teresa Valenti
Department of Medicine, University of Verona, Verona, Italy
Luca Dalle Carbonare
Department of Medicine, University of Verona, Verona, Italy
Gabriel Siracusano
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
Nigel Temperton
Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent and Greenwich, UK
Natalia Tiberti
Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (VR), Italy
Silvia Stefania Longoni
Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (VR), Italy
Massimo Pizzato
Department of Cellular, Computational and Integrative Biology, University of Trento, Povo (TN), Italy
Silvia Accordini
Department of Cellular, Computational and Integrative Biology, University of Trento, Povo (TN), Italy
Tobia Fantoni
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy
Lucia Lopalco
Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy
Alberto Beretta
Solongevity Research, Milan, Italy
Zeno Bisoffi
Department of Infectious, Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar (VR), Italy; Department of Diagnostics and Public Health, University of Verona, Verona, Italy
Donato Zipeto
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; Corresponding author.
Summary: Background: Currently, evaluation of the IgG antibodies specific for the SARS-CoV-2 Spike protein following vaccination is used worldwide to estimate vaccine response. Limited data are available on vaccine-elicited IgM antibodies and their potential implication in immunity to SARS-CoV-2. Methods: We performed a longitudinal study to quantify anti-S SARS-CoV-2 IgG and IgM (IgG-S and IgM-S) in health care worker (HCW) recipients of the BNT162b2 vaccine. Samples were collected before administration (T0), at the second dose (T1) and three weeks after T1 (T2). The cohort included 1584 immunologically naïve to SARS-CoV-2 (IN) and 289 with history of previous infection (PI). Findings: IN showed three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing at T1 (37.4%) and (c) IgM appearing after IgG (26.3%). Coordinated IgM-S/IgG-S responses were associated with higher IgG titres. In IgM-S positive PI, 64.5% were IgM-S positive before vaccination, whereas 32% and 3.5% developed IgM-S after the first and second vaccine dose, respectively. IgM-S positive sera had higher pseudovirus neutralization titres compared to the IgM-S negative. Interpretation: Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody levels and virus-neutralizing activity. The unconventional IgG-S positive/IgM-S negative responses may suggest a recruitment of cross coronaviruses immunity by vaccination, warranting further investigation. Funding: Italian Ministry of Health under “Fondi Ricerca Corrente”- L1P5 and “Progetto Ricerca Finalizzata COVID-2020-12371675”; FUR 2020 Department of Excellence 2018-2022, MIUR, Italy; The Brain Research Foundation Verona.
