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Background

Data on the incidence of RSV reinfection are scarce. We estimated medically-attended reinfection rates within each RSV year and season from 2011-2019.

Methods

Using claims data from private insurance enrollees, we established cohorts of children <5 years who were followed to ascertain annual (July 1-June 30) and seasonal (November - February) RSV recurrence estimates. Unique RSV episodes included inpatient encounters with RSV diagnosis with ≥30 days gap between hospitalization, and outpatient encounters ≥30 days apart from each other as well as from inpatient encounters. The risk of annual and seasonal re-infection was calculated as the proportion of children with a subsequent RSV episode in the same RSV year/season.

Results

Over the 8 assessed study years/seasons, the total annual number of initial RSV episodes ranged from 10,049 – 14,077 (inpatient = 964-1,402), representing 1.59 – 1.82% of children. The number of annual reinfections was 325 – 791 (inpatient = 22-49), ranging from 0 – 5 per initial RSV episode. The annual proportion of children re-infected ranged from 2.61% (95% CI=2.31%-2.93%) to 4.76% (4.41%-5.12%), mostly requiring outpatient care (2.44% (2.15%-2.75%) to 4.45% (4.12%-4.81%) rather than inpatient care (0.20% (0.12%-0.30%) to 0.35% (0.26%-0.46%)). The proportion of children with reinfections declined with age.

Conclusions

A small proportion of young children experience RSV reinfections that require medical attendance.

Background

In 2006, the American Academy of Paediatrics (AAP) published a clinical practice guideline recommending that infants born less than 32-weeks gestation receive Palivizumab if aged less than twelve months at the start of the RSV season. An updated guideline in 2014 advised that only infants less than 29-weeks should receive Palivizumab in the absence of other indications. The aim of this study was to determine the impact of changing guidelines on RSV-related hospital admissions, management and outcome among infants born <32 weeks in Ireland.

Methods

Data was collected prospectively for all patients admitted with RSV bronchiolitis from 2010-2020 to paediatric intensive care units (PICU) in Ireland. The two groups of interest were infants born <32 weeks gestation admitted from 2010-2014 and from 2015-2020. Data included demographic variables, background, management and outcome. Categorical variables were analysed using Chi-squared test. Continuous variables were analysed using Mann-Whitney test.

Results

There were 823 RSV-related PICU admissions in Ireland between 2010 and 2020, 99 (12%) of which were among infants born <32 weeks gestation. The total number of Palivizumab prescriptions decreased nationally from a median of 1335 doses/year in 2010-2015 to 1055 from 2015-2020. Significantly fewer infants in the 29-32 week gestation group were receiving Palivizumab at admission post 2015, 18.8% vs 66.7%, p=0.03. The average length of PICU admission, requirement for mechanical ventilation or duration of mechanical ventilation was not significantly different between groups. No infants in either group died.

Conclusions

Adoption of the 2014 updated AAP-guideline on Palivizumab use was associated with reduced prescription in the 29-32 week gestation group in Ireland. This change was not associated with in an increased frequency of PICU admission, mechanical ventilation or worse outcome among infants <32 weeks gestation.

Background

Respiratory syncytial virus (RSV) is the most common cause of respiratory viral infections in children worldwide. The risk factors for severe RSV infections are young age, premature birth, cardiac and pulmonary diseases and immunodeficiency. Children who are HIV exposed and uninfected (CHEU) are known to be susceptible to infections in early life. The burden of RSV in this population has been demonstrated in developing countries but poorly studied in high-income countries. The aim of our study is to evaluate the incidence of hospitalizations linked to RSV in CHEU born in Belgium.

Methods

Between December 2010 and November 2013, as part at the ELIKYA study , 130 HIV-affected and 120 uninfected pregnant women were recruited at Saint-Pierre Hospital, Brussels. Their children were followed up until the age of 1 year. Levels of RSV antibodies were measured at 6 months of age to define rates of natural infections.

Results

During the first year of life, 46 hospitalizations for infections have occurred including 11 admissions for RSV infections. Despite similar rate of seroconversion for RSV at 6 months of life, the RSV hospitalizations' incidence was 8.5 times higher in CHEU compared to CHU (IR= 7.7 per 100 person-years in CHEU vs 0.9 per 100 person-years in unexposed controls). Among CHEU, initiation of maternal ARV therapy before pregnancy was a protective factor. All hospitalizations occurred before the age of 6 months of age.

Conclusions

Our study demonstrates that despite similar exposure to RSV, CHEU born in a high-income country show excess hospitalizations linked to RSV infection. Because of their vulnerability to severe RSV infection among others infections, CHEU should be closely followed up and targeted for preventative measures including immunization.

Background

RSV vaccines are under development to allow prevention of RSV disease in infants through passive immunity with maternal antibodies. We assessed immunogenicity of the investigational RSVPreF3 vaccine in mothers and placental transfer of maternal antibodies to fetus.

Methods

In this ongoing phase II, observer-blind, placebo-controlled, multi-country trial, 213 healthy pregnant women aged 18-40 years were randomised 1:1:1 and received a single 60 or 120 µg dose of RSVPreF3 (60 or 120 RSVPreF3 group) or placebo between 28^0/7-33^6/7 weeks of gestation. Levels of maternal anti-RSVPreF3 IgG-specific antibodies and RSV-A neutralising antibodies (nAb) measured pre-vaccination, on day 31 and at delivery, including cord blood levels, are shown here.

Results

On day 31, the maternal anti-RSVPreF3 IgG antibody geometric mean concentrations (GMCs) increased 13.6-fold in the 60 RSVPreF3 group and 17.3-fold in the 120 RSVPreF3 group (placebo: 1.0-fold) compared to baseline; at delivery a 10.6- and 10.7-fold increase versus baseline, respectively, was observed (placebo: 0.9-fold) (Figure 1A). On day 31, RSV-A nAb geometric mean titres (GMTs) were 12.4-fold and 15.5-fold higher in the 60 and 120 RSVPreF3 groups, respectively (placebo: 1.2-fold); at delivery, the fold-increase was 8.4 in the 60 RSVPreF3 group and 10.0 in the 120 RSVPreF3 group (placebo: 1.2-fold) (Figure 1B). RSVPreF3 IgG GMCs and RSV-A nAb GMTs were higher in infants of RSVPreF3-vaccinees than in those of placebo recipients (Figure 1A and 1B). At delivery, the GM of placental transfer ratio of RSVPreF3 IgG antibodies was 1.6 and 1.8 in the 60 and 120 RSVPreF3 groups, respectively (Figure 1A).

Conclusions

The investigational RSVPreF3 vaccine induced a robust immune response in pregnant women at all timepoints that is efficiently transferred to fetuses, leading to high neutralising cord blood titres.

Funding: GlaxoSmithKline Biologicals SA

Clinical Trial Registration

NCT04126213

Background

Currently there are no licensed RSV vaccines available. We report immunogenicity results in infants vaccinated with 2 different regimens and dose levels of ChAd155-RSV, a chimpanzee adenovirus-vectored vaccine encoding RSV proteins F, N and M2-1.

Methods

In this phase I/II observer-blind, controlled study conducted in 13 countries, infants aged 6-7 months were randomized (1:1:1) to receive either 1 dose of ChAd155-RSV 1.5x10¹⁰viral particles (vp) and 1 placebo dose (RSV_1D group), 2 doses of ChAd155-RSV 5x10¹⁰vp (RSV_2D group) or 2 comparator doses (placebo or vaccine [meningococcal or pneumococcal]) on days 1 and 31. We evaluated RSV-A neutralizing antibody (NAb) geometric mean titers (GMTs; ED60) and anti-RSV F IgG geometric mean antibody concentrations (GMCs; EU/mL). We present results from RSV unexposed infants (seronaïve) as assessed by serologic testing of RSV-A NAbs at baseline.

Results

Of 201 infants enrolled, 155 were seronaïve and analyzed for immunogenicity up to day 61. At days 31 and 61, RSV-A NAb GMTs were significantly higher in RSV groups compared to baseline and comparator group (Figure A). The high dose vaccine (RSV_2D) induced greater RSV-A NAbs response as compared to low dose (RSV_1D) from baseline to day 31 (4.4-fold vs 2.9-fold increase, respectively). The second RSV vaccine dose (RSV_2D) induced a further increase of >2.6-fold in RSV-A NAb GMTs at day 61. In total, an 11.8-fold increase from baseline (GMT:21.2) to day 61 (GMT:246.0) was observed. Anti-RSV-F IgG followed similar trends, with increases at day 61 of 32.9-fold (GMC:2300.0; RSV_1D) and 150.0-fold (GMC:9082.3; RSV_2D) (Figure B).

Conclusions

In RSV seronaïve infants, ChAd155-RSV vaccine induced a significant binding and neutralizing RSV antibody responses which were greater at the higher dose level and increased after the second dose.

Funding: GlaxoSmithKline Biologicals SA

Clinical Trial Registration

ClinicalTrials.gov 03636906

Background

Despite the significant burden respiratory syncytial virus (RSV) causes in children, there is no approved vaccine for RSV disease. We evaluated the safety and immunogenicity of the experimental vaccine Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilised in the pre-fusion conformation.

Methods

In this phase 1/2a double-blind study, RSV-seropositive toddlers aged 12–24 months were randomised 2:1 to receive 2 doses of Ad26.RSV.preF (5×10¹⁰ viral particles) or placebo intramuscularly, with approximately 28 days between doses. Safety, immunogenicity and RSV infections were assessed for up to one-year post-Dose 1.

Results

In total, 24 participants received Ad26.RSV.preF and 12 received placebo. No vaccine-related serious adverse events occurred within 28 days post-vaccination with Ad26.RSV.preF. Solicited (local or systemic) adverse events (AEs) commonly occurring in Ad26.RSV.preF and placebo recipients were injection site pain/tenderness (66.7% and 50.0%) and irritability/crying (91.7% for both groups). Fever (≥38.0ºC) was observed in 58.3% of Ad26.RSV.preF recipients and 25.0% of placebo recipients; the majority of events resolved within 2 days. Geometric mean titers (GMT) of neutralizing antibodies to RSV A2 increased in Ad26.RSV.preF recipients from 121 (95% CI:76;191) at baseline to 1,608 (95% CI:730;3,544) at 28 days post-Dose 1 and 2,235 (95% CI:1,586;3,150) post-Dose 2 at Day 57 and remained stable in placebo recipients. Pre- and post-F-specific antibodies increased substantially from baseline post-vaccination with Ad26.RSV.preF. CD4+ and CD8+ T cell responses were elicited in the AD26.RSV.preF group, with a predominant Th1-skewed phenotype. RSV infection was PCR-confirmed in one (4.2%) Ad26.RSV.preF recipient compared with five (41.7%) placebo recipients.

Conclusions

Ad26.RSV.preF was well tolerated, elicited humoral and cellular immune responses. Further studies evaluating the immunogenicity and reactogenicity of Ad26.RSV.preF are ongoing in RSV-seronegative toddlers aged 12–24 months.

Clinical Trial Registration

Protocol number: VAC18194RSV2001

Clinical trial number: NCT03303625

EudraCT Number: 2017-001345-27

Clinical Registry number: CR108371