Longitudinal immunogenicity cohort study of SARS-CoV-2 mRNA vaccines across individuals with different immunocompromising conditions: heterogeneity in the immune response and crucial role of Omicron-adapted booster dosesResearch in context
Annalisa Ciabattini,
Elena Pettini,
Fabio Fiorino,
Jacopo Polvere,
Simone Lucchesi,
Chiara Coppola,
Simone Costagli,
Gabiria Pastore,
Anna Sicuranza,
Monica Tozzi,
Arianna Lippi,
Francesca Panza,
Monica Bocchia,
Alessandro Bucalossi,
Guido Garosi,
David Bennett,
Sonia Bernazzali,
Massimiliano Fabbiani,
Francesca Montagnani,
Donata Medaglini
Affiliations
Annalisa Ciabattini
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy; Corresponding author. Department of Medical Biotechnologies, University of Siena, Siena, Italy.
Elena Pettini
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Fabio Fiorino
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy; Department of Medicine and Surgery, LUM University “Giuseppe Degennaro”, Bari, Italy
Jacopo Polvere
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Simone Lucchesi
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Chiara Coppola
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Simone Costagli
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Gabiria Pastore
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Anna Sicuranza
Haematology Unit, Department of Medical Science, Surgery and Neuroscience, University Hospital of Siena, Siena, Italy
Monica Tozzi
Cellular Therapy Unit, Department of Innovation, Experimentation, Clinical and Translational Research, University Hospital of Siena, Siena, Italy
Arianna Lippi
Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy
Francesca Panza
Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy
Monica Bocchia
Haematology Unit, Department of Medical Science, Surgery and Neuroscience, University Hospital of Siena, Siena, Italy
Alessandro Bucalossi
Cellular Therapy Unit, Department of Innovation, Experimentation, Clinical and Translational Research, University Hospital of Siena, Siena, Italy
Guido Garosi
Department of Medical Science, Nephrology, Dialysis and Transplantation Unit, University Hospital of Siena, Italy
David Bennett
Respiratory Disease and Lung Transplant Unit, University of Siena, University Hospital of Siena, Italy
Sonia Bernazzali
Department of Cardiac Surgery, University of Siena, Siena, Italy
Massimiliano Fabbiani
Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy
Francesca Montagnani
Department of Medical Sciences, Infectious and Tropical Diseases Unit, University Hospital of Siena, Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy
Donata Medaglini
Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy
Summary: Background: Individuals with primary and secondary immunodeficiencies, being more susceptible to infections, are a priority for vaccination. Here, we determined and compared in a longitudinal study the immune response elicited by SARS-CoV-2 vaccination across different groups of individuals who are immunocompromised. Methods: In the PatoVac_COV longitudinal prospective single-centre study, the spike-specific B cell and antibody responses to SARS-CoV-2 mRNA vaccination were compared across 5 different groups of individuals with haematological malignancies, hematopoietic stem cell (HCT) or solid organ transplantation (SOT), undergoing haemodialysis, and people living with HIV (PLWH), for a total of 585 participants. Data from participants who were immunocompromised were compared to a group of 123 participants who were immunocompetent. Blood samples were collected before and after each vaccine administration, up to 2 years. Findings: A different immune responsiveness was observed after the first two vaccine doses, with haematological, haemodialysis, and SOT participants showing reduced responsiveness compared to HCT and PLWH, and relative to the comparison group. Spike-specific B cell response was both slower and lower in all groups except in PLWH when compared to participants who were immunocompetent. However, the first booster dose enhanced both the B and the antibody responses in all groups, that persisted up to 2 years after the first vaccine administration. The administration of Omicron-adapted booster vaccines promoted a primary BA.2 RBD-specific B cell response, especially in participants who were immunocompromised. Despite repeated vaccinations, a subset of persistent low-responders, especially among SOT, was identified. Interpretation: Our study highlights the heterogeneous immune response across individuals with different pathologies, the pivotal role of the first booster dose, the primary activation of Omicron-specific B cells elicited by updated variant-adapted vaccines and the persistence of low-responders despite multiple vaccine administrations. These aspects have a clinical relevance for planning vaccination schedules tailored for individuals with different immunocompromising conditions. Funding: This work was supported by funds from the Department of Medical Biotechnologies of the University of Siena, and from EU within the NextGenerationEU-MUR PNRR Tuscany Health Ecosystem (Project no ECS00000017-THE).
