Characterization of antibody response in neuroinvasive infection caused by Toscana virus.
OBJECTIVE
Among sandfly-borne pathogens, Toscana virus (TOSV) is a prominent cause of summer meningitis in Mediterranean Europe. Here, we assessed the kinetics of anti-TOSV antibodies over time in 41 patients diagnosed with TOSV meningitis or meningoencephalitis in northeastern Italy.


METHODS
Acute and follow-up serum samples were collected up to 20 months after diagnosis of TOSV infection and tested for the presence of specific antibody using immunoenzymatic and indirect immunofluorescence assays. In addition, maturation of anti-TOSV IgG over time was evaluated as well as production of neutralizing antibodies.


RESULTS
Specific IgM and IgG response was present at diagnosis in 100% of patients; TOSV-specific IgM and IgG were detected in patients' sera up to 6 and 20 months after diagnosis, respectively. The avidity index (AI) increased over the first month after infection in 100% of patients and most cases exceeded 60% by Day 30 post infection. The AI subsequently plateaued then declined at 20 months after diagnosis. Finally, neutralization assay to TOSV was performed in 217 sera collected from 41 patients; 69.6% of tested samples resulted in reactive and moderate levels of neutralizing antibodies observed during all phases of infection despite high titres of total anti-TOSV IgG.


CONCLUSIONS
Specific antibody response develops rapidly and is long-lasting for neuroinvasive TOSV infection. Serodiagnosis of neuroinvasive TOSV requires simultaneous detection of specific IgM and IgG. Moderate levels of neutralizing antibodies were maintained over the study period, while the protective role of antibodies lacking neutralizing activity is unclear and requires further evaluation.
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy; Unit of Microbiology, The Romagna Hub Laboratory, Pievesestina, Italy. Electronic address: anna.pierro@auslromagna.it.
A
A
Pierro
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy.
S
S
Ficarelli
UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Univ - IRD 190 - Inserm1207 - EHESP) & Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
N
N
Ayhan
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy.
S
S
Morini
Infectious Disease Unit, Department of Medical and Surgical Science, University of Bologna, Bologna, Italy.
L
L
Raumer
Infectious Disease Unit, Department of Medical and Surgical Science, University of Bologna, Bologna, Italy.
M
M
Bartoletti
Infectious Disease Unit, G.B. Morgagni-Pierantoni Hospital, Forlì, Italy.
A
A
Mastroianni
Infectious Disease Division, Reggio Emilia Hospital, Reggio Emilia, Italy.
F
F
Prati
Infectious Disease Division, Reggio Emilia Hospital, Reggio Emilia, Italy.
S
S
Schivazappa
Emergency Department, St. Maria della Scaletta, Imola, Italy.
P
P
Cenni
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy.
C
C
Vocale
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy.
G
G
Rossini
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy.
P
P
Gaibani
Unit of Microbiology, The Romagna Hub Laboratory, Pievesestina, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
V
V
Sambri
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
M P
MP
Landini
Infectious Disease Unit, Department of Medical and Surgical Science, University of Bologna, Bologna, Italy.
R E
RE
Lewis
UMR "Emergence des Pathologies Virales" (EPV: Aix-Marseille Univ - IRD 190 - Inserm1207 - EHESP) & Fondation IHU Méditerranée Infection, APHM Public Hospitals of Marseille, Marseille, France.
R N
RN
Charrel
Unit of Microbiology, CRREM Laboratory, St. Orsola-Malpighi University Hospital, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
S
S
Varani
D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D002044:Bunyaviridae Infections / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008587:Meningitis, Viral / Q000276:immunology*; D008875:Middle Aged; D029301:Sandfly fever Naples virus / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M
Antibody production; IgG avidity test; Neutralizing antibodies; Patients' follow-up; Toscana virus infection