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SARS-CoV-2 Vaccination Elicits Unconventional IgM Specific Responses in Naïve and Previously COVID19-Infected Individuals

28 Pages Posted: 4 Nov 2021

See all articles by Alessandra Ruggiero

Alessandra Ruggiero

Bambino Gesù Children's Hospital - Academic Department of Pediatrics (DPUO); University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences

Chiara Piubelli

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Lucia Calciano

University of Verona - Department of Diagnostics and Public Health

Simone Accordini

University of Verona - Department of Diagnostics and Public Health

Maria Teresa Valenti

University of Verona - Department of Medicine

Luca Dalle Carbonare

University of Verona - Department of Medicine

Gabriel Siracusano

Università Vita-Salute San Raffaele - Transplantation and Infectious Diseases, Experimental Imaging Center

Lucia Lopalco

Università Vita-Salute San Raffaele - Transplantation and Infectious Diseases, Experimental Imaging Center

Nigel Temperton

University of Kent - Viral Pseudotype Unit

Natalia Tiberti

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Silvia Stefania Longoni

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Massimo Pizzato

University of Trento - Department of Cellular, Computational and Integrative Biology

Silvia Accordini

University of Trento - Department of Cellular, Computational and Integrative Biology

A.M.S.L.V. Group

Ambulatorio Medico San Luca Villanuova

Tobia Fantoni

University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences

Alberto Beretta

Solongevity Research

Zeno Bisoffi

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology

Donato Zipeto

University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences

More...

Abstract

Background: IgG antibodies specific for the SARS-CoV-2 Spike protein are under intensive investigation for the urgent need to identify a correlate of protective immunity in individuals vaccinated with licensed and candidate COVID-19 vaccines. 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 IgG and IgM antibodies specific for the SARS-CoV-2 spike protein (IgG-S and IgM-S) in 1873 health care worker (HCW) recipients of the BNT162b2 (Comirnaty) vaccine. Samples were collected before administration (T0), at the second dose (T1) and three weeks after the second dose (T2). The cohort included 1584 immunologically naïve to SARS-CoV-2 (IN) and 289 had a history of previous infection (PI).  

Findings: In IN we identified three patterns of responses: (a) IgG positive/IgM negative (36.1%), (b) coordinated IgM-S/IgG-S responses appearing three weeks after the first dose (37.4%) and (c) delayed IgM appearing after IgG (26.3%). Coordinated IgM-S/IgG-S responses were associated with higher IgG titers. Of the 289 PI vaccinees, 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 titers compared to the IgM-S negative. Similar results were observed in individuals who received either Moderna or Astrazeneca. 

Interpretation: Coordinated expression of IgG-S and IgM-S after vaccination was associated with a significantly more efficient response in both antibody titers and virus-neutralizing activity, representing a potential correlate of protection. Instead, the unconventional IgG-S positive/IgM-S negative responses may be suggestive of a recruitment of cross coronaviruses immunity by vaccination, warranting further investigation.

Funding Information: This work was supported by the Italian Ministry of Health under “Fondi Ricerca Corrente”- L1P5 and “Progetto Ricerca Finalizzata COVID-2020-12371675” to IRCCS Sacro Cuore Don Calabria Hospital, by FUR 2020 Department of Excellence 2018-2022, MIUR, Italy and by The Brain Research Foundation Verona.

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: University of Verona biobank (Ethics Committee approval prot. N. 1538). Tropica Biobank of the IRCCS Sacro Cuore Don Calabria Hospital (Ethics Committee approval prot. N. 17985). All participants signed informed consent.

Keywords: COVID-19, SARS-CoV-2, IgM, IgG, Comirnaty, unconventional response, neutralization assay

Suggested Citation

Ruggiero, Alessandra and Piubelli, Chiara and Calciano, Lucia and Accordini, Simone and Valenti, Maria Teresa and Dalle Carbonare, Luca and Siracusano, Gabriel and Lopalco, Lucia and Temperton, Nigel and Tiberti, Natalia and Longoni, Silvia Stefania and Pizzato, Massimo and Accordini, Silvia and Group, A.M.S.L.V. and Fantoni, Tobia and Beretta, Alberto and Bisoffi, Zeno and Zipeto, Donato, SARS-CoV-2 Vaccination Elicits Unconventional IgM Specific Responses in Naïve and Previously COVID19-Infected Individuals. Available at SSRN: https://ssrn.com/abstract=3956430 or http://dx.doi.org/10.2139/ssrn.3956430

Alessandra Ruggiero

Bambino Gesù Children's Hospital - Academic Department of Pediatrics (DPUO) ( email )

Rome
Italy

University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences ( email )

Verona
Italy

Chiara Piubelli

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Lucia Calciano

University of Verona - Department of Diagnostics and Public Health ( email )

Verona
Italy

Simone Accordini

University of Verona - Department of Diagnostics and Public Health ( email )

Verona
Italy

Maria Teresa Valenti

University of Verona - Department of Medicine ( email )

Verona
Italy

Luca Dalle Carbonare

University of Verona - Department of Medicine ( email )

Verona
Italy

Gabriel Siracusano

Università Vita-Salute San Raffaele - Transplantation and Infectious Diseases, Experimental Imaging Center ( email )

Milan, 20132
Italy

Lucia Lopalco

Università Vita-Salute San Raffaele - Transplantation and Infectious Diseases, Experimental Imaging Center ( email )

Milan, 20132
Italy

Nigel Temperton

University of Kent - Viral Pseudotype Unit ( email )

CT2 7NP
United Kingdom

Natalia Tiberti

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Silvia Stefania Longoni

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Massimo Pizzato

University of Trento - Department of Cellular, Computational and Integrative Biology ( email )

Italy

Silvia Accordini

University of Trento - Department of Cellular, Computational and Integrative Biology ( email )

Italy

A.M.S.L.V. Group

Ambulatorio Medico San Luca Villanuova

Italy

Tobia Fantoni

University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences ( email )

Verona
Italy

Alberto Beretta

Solongevity Research ( email )

Milan
Italy

Zeno Bisoffi

Negrar di Valpolicella - Dept of Infectious Tropical diseases and Microbiology ( email )

Verona
Italy

Donato Zipeto (Contact Author)

University of Verona - Department of Neurosciences, Biomedicine and Movement Sciences ( email )

Verona
Italy

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