Welcome to the ESPID 2021 Meeting Calendar

Background

Cytomegalovirus is the most common congenital viral infection, with birth prevalence ranging 0.2-6.1% worldwide. We will present final safety and immunogenicity data from the Phase 1 trial of mRNA-1647, an mRNA-based vaccine encoding CMV pentamer complex (PC) and glycoprotein B (gB) antigens.

Methods

This Phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study evaluated safety and immunogenicity of 30, 90, 180, or 300 ug of mRNA-1647 or placebo administered on a 0, 2, 6-month schedule through 12 months post 3^rd vaccination in 154 healthy CMV-seronegative and CMV-seropositive adults 18-49 years old.

Results

A planned interim analysis at Month 12 (6 months post 3rd vaccination) indicated injection site pain (54-100%) as the most common solicited local adverse reaction (AR) over the 3-dose schedule across mRNA groups, and the most common solicited systemic ARs were headache (6-89%), fatigue (12-82%), myalgia (0-78%) and chills (6-82%). Antigen-specific antibody geometric mean titers (GMTs) increased with dose in both CMV-seronegative and CMV-seropositive groups. In the CMV-seronegative 30, 90, and 180 μg treatment groups, neutralizing antibody (nAb) GMTs against epithelial cell infection were ≥3.6-fold over the CMV-seropositive baseline GMT in the 90 μg and 180 μg treatment groups, and nAb GMTs against fibroblast infection approximated the CMV-seropositive baseline GMT in the 90 μg and 180 μg treatment groups. In CMV-seropositive treatment groups, nAb geometric mean ratios over baseline ranged between 14 and 31 against epithelial cell infection and between 6 and 8 against fibroblast infection.

Conclusions

This Phase 1 study showed mRNA-1647 to be generally well-tolerated. Vaccination with mRNA-1647 induced antigen-specific immune responses in CMV-seronegative participants and boosted immune responses in CMV-seropositive participants. This first-in-human trial demonstrates the potential of a mRNA vaccine to prevent CMV infection and supports its further development.

Clinical Trial Registration

ClinicalTrials.gov Identifier: NCT03382405

Background

Neonatal Herpes Simplex Virus (HSV) infection may cause severe morbidity and mortality. With cases increasing, optimising short and long-term management for infants is important to minimise complications.

Aciclovir prophylaxis reduces recurrence of central nervous system (CNS) disease, which may occur in up to 8% of cases. Daily prophylaxis over a 6-month period has been shown to improve neurodevelopmental outcomes. We present outcomes and recurrence rates for this treatment course.

Methods

We reviewed neonates under the care of three tertiary centres with HSV disease, who presented at less than 90 days of age. Demographics, including neonatal history, clinical presentation, initial investigations and treatment were reviewed (Table 1). Follow-up, including recurrence rate on and after prophylactic aciclovir or valaciclovir and management were recorded.

Results

Of 21 patients, six (28%) had HSV-1, 14 (66%) HSV-2 and one unknown. 13 infants were born at term, eight preterm (<37 weeks). 57% presented with central nervous system (CNS) disease. Seven (33%) had recurrences on prophylaxis, despite good adherence to treatment, and 13 (61%) after stopping prophylaxis. All recurrences were skin eruptions. Premature babies were more likely to have recurrences than term babies. 50% of preterms versus 23% of term babies had recurrences on prophylaxis. After discontinuing prophylaxis, 75% of preterms versus 53% term babies had recurrences.

Conclusions

In this small cohort of infants with neonatal HSV disease, after a course of prophylaxis there was still frequent recurrence of skin lesions, but reassuringly there was no CNS recurrence. Of note, recurrence appeared more common in babies born prematurely, implying a less effective immune response to HSV. Further research is needed to investigate the ontogeny of the immune response to HSV in infants of different gestations.

Background

Toxoplasma Gondii is a parasite with a transplacental passage. Evaluation of newborns exposed to Toxoplasmosis in pregnancy includes ophthalmologic and auditory tests, neurologic examination at birth and serological evaluation until 12 months, to assess the possibility of congenital infection. The aim of this study is to evaluate serological testing timeline in neonates exposed to Toxoplasmosis in pregnancy.

Methods

This is a single center, population-based cohort study of neonates referred for prenatal exposure to Toxoplasmosis from 2014 to 2019. Neonates underwent clinical, laboratory and instrumental investigation for at least 12 months as recommended by national guidelines. A total of 670 neonates were referred to the Perinatal Infection Unit of the University Federico II of Naples. Six hundred thirty-six (95%) completed the serological follow up until twelve months.

Results

Specific IgG antibodies negativization occurred in 628 (98.7%) within 5 months. At 9 and 12 months, all neonates had negative IgG. Initial neonatal IgG antibody titer =300 UI/ml was associated with time to negativization (241.5±38.2 days when above threshold vs. 137.1±42.6 days when below it; p<0.0001). Initial maternal IgG antibody titer = 300 UI/ml was also associated to time to negativization in the infant (196.1±35.7 days above the cut off vs 135.4±42.6 days below it; p<0.0001). Specific antibody negativization was irreversible in all patients.

Conclusions

Initial maternal and neonatal anti Toxoplasma IgG titers are significantly associated with the time to antibody negativization. These biomarkers can be useful to customize the follow up duration and avoid unnecessary blood drawing.