Non Primary HCMV Infection: Natural History and Immune Response

NCT ID: NCT06337955

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 204 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-06-06
• Study Completion Date: 2024-12-31

Brief Summary

The goals of this observational study are: i) investigate the natural history of non-primary (i.e. reactivation and reinfection) HCMV infection in HCMV-seropositive Italian women and the relevant humoral and cell-mediated immune response; ii) reliably distinguish between reactivation and reinfection.

Prerequisite of the study is the availability of a maternal HCMV strain at baseline (original strain) to which subsequent strains detected during follow-up are compared in order to distinguish between reactivation (original strain) or reinfection (new strain).

To increase the likelihood of exposure to different HCMV strains, the study population is restricted to mothers of children attending day care centers.

Detailed Description

Eligible women will be identified and enrolled during pregnancy or at delivery. Consenting mothers will be tested for HCMV DNA in saliva, urine and vaginal swab at delivery and/or at the first scheduled post-partum visit (2-4 months after delivery). In addition, mothers and children will be tested for presence of HCMV DNA in milk and saliva samples, respectively.

A mother-child pair is considered HCMV-DNA positive and, therefore, suitable for continuing the study (i.e. the 12 months follow up after admission of the child to day care center) whenever viral DNA is detected in clinical samples of either the mother or the child or both. In fact, when viral DNA is undetectable in the mother but is present in the saliva of a 2-4 month old infant it can be reasonably assumed that the strain is of maternal origin.

The study does not require any modification in the normal mother-child relationship and participating mothers will be encouraged to behave normally. However, mothers will be asked to fill in a short questionnaire about basic behaviours in daily child care (i.e. frequency of hand washing, kissing of the infant, sharing of food...).

The following clinical samples will be collected from mothers and infants at indicated times (T):

T0. Delivery:

• mother: saliva, urine, vaginal swab, peripheral blood.

T1. 2-4 months after delivery:

• mother: saliva, urine, vaginal swab, milk, peripheral blood;
• infant: saliva swab.

T2. Admission of the infant to day care center:

• mother: saliva swab, urine, vaginal swab, peripheral blood;
• infant: saliva swab.

T3-T6. Every 3 months after admission of the infant for one year:

• mother: saliva swab, urine, vaginal swab, peripheral blood;
• infant: saliva swab.

Virological analyses:

1. HCMV DNA detection and quantification in blood and body specimens;

2. sequence analysis of selected variable viral genes and determination of strain(s) diversity (whole genome will also be sequenced when possible);

3. HCMV isolation from collected specimens (when HCMV DNA shedding is detected).

Immunological analyses:

• antibody response:

1. IgG and IgM to whole HCMV antigens;

2. IgG to glycoprotein complexes gHgLpUL128L, gHgLgO, gB;

3. neutralizing (Nt) Ab blocking infection of epithelial/endothelial cells and fibroblasts.

• T cell response:

1. ex vivo cytokine (IFNgamma/IL-2) production;

2. ex vivo proliferation after stimulation with HCMV antigens;

3. differentiation state of HCMV specific T cells (CCR7, CD45RA, IL7R expression.

Questionnaire:

Participating mothers will also be invited to fill in a questionnaire concerning their daily habits in terms of caring for their children.

Conditions

Cytomegalovirus Infections

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Adult (≥18 years of age) HCMV IgG-positive, breast feeding* woman.
• Willingness to enroll the infant in a public or private day care facility with at least 5 attendees at ≤ 12 months of age.
• Willingness to participate in the study.
• In case of foreign origin, language skills sufficient to understand information material and give informed consent.
• Written informed consent. * Breast feeding not required in case of availability of HCMV DNA-positive samples from the mother and/or fetus and/or newborn.

Exclusion Criteria

• Congenital or acquired immunodeficiency
• Immunosuppressive therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Università degli Studi di Pavia

UNKNOWN

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Fondazione Regionale per la Ricerca Biomedica

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: lead

Responsible Party

Daniele Lilleri

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniele Lilleri, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Policlinico San Matteo

Locations

Fondazione IRCCS Policlinico San Matteo

Pavia, PV, Italy

Countries

Italy

Other Identifiers

20170007596

Identifier Type: -

Identifier Source: org_study_id