Safety, reactogenicity and immunogenicity of the human rotavirus vaccine in preterm European Infants: a randomized phase IIIb study.
BACKGROUND
Rotavirus disease is more severe in preterm infants than in full-term infants. This study assessed the safety, reactogenicity and immunogenicity of a human rotavirus vaccine, RIX4414, in European preterm infants.


METHODS
A total of 1009 preterm infants were randomized (2:1, vaccine:placebo) and stratified into 2 groups: 20% of early (27-30 weeks, group 1) and 80% of late (31-36 weeks, group 2) gestational age preterm infants in each group. Two doses of RIX4414/placebo were administered to these preterm infants according to the recommended chronologic age for full-term infants with an interval of 30-83 days between doses. Serious adverse events were recorded throughout the study period. Solicited and unsolicited adverse events were recorded for 15 and 31 days post-each dose. Antirotavirus IgA concentrations (enzyme-linked immunosorbent assay cutoff = 20 U/mL) and geometric mean concentration were determined pre-dose 1 and 30-83 days post-dose 2 in a subset of 300 infants. This study is registered with ClinicalTrials.gov, number NCT00420745 (eTrack106481).


RESULTS
Serious adverse events were reported at a similar frequency in both groups (P = 0.266). Fifty-seven infants reported at least 1 serious adverse event (5.1% [3.5-7.0] in the RIX4414 group and 6.8% [4.3-10.0] in the placebo group). During the 15-day postvaccination follow-up period, diarrhea, vomiting and fever occurred at a similar frequency in both groups; fever could have been due to concomitant vaccines. Five cases (RIX4414 = 3, Placebo = 2) of rotavirus gastroenteritis were reported. The onset of rotavirus gastroenteritis in the RIX4414 group was 1-5 days after vaccination (vaccine strain identified in all cases) and in the placebo group it was 3-4 days after receiving placebo (wild-type rotavirus identified from both cases). Antirotavirus IgA seroconversion rates at 30-83 days post-dose 2 were 85.7% (79.0-90.9) in the RIX4414 group and 16.0% (8.8-25.9) in the placebo group. Geometric mean concentrations were 202.2 U/mL (153.1-267.1) in the RIX4414 group and <20 U/mL in the placebo group. Seroconversion rate in groups 1 and 2 in RIX4414 recipients were 75.9% (95% confidence interval [CI]: 56.5-89.7%) and 88.1% (95% CI: 80.9-93.4%), respectively; the geometric mean concentrations in the respective groups were 110.2 U/mL (95% CI: 56.1-216.5) and 234.8 U/mL (95% CI: 173.4-318.0; exploratory analysis).


CONCLUSIONS
Two doses of RIX4414 were immunogenic and well-tolerated in European preterm infants.
La Paz Hospital, Madrid, Spain. fomenaca.hulp@salud.madrid.org
Felix
F
Omenaca
Jean
J
Sarlangue
Leszek
L
Szenborn
Marta
M
Nogueira
Pemmaraju V
PV
Suryakiran
Igor V
IV
Smolenov
Htay H
HH
Han
D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005759:Gastroenteritis / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D005865:Gestational Age; D006801:Humans; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000097:blood; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated