Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.
BACKGROUND
A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children.


METHODS
A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age.


RESULTS
Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients.


CONCLUSIONS
Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.
Salinas
Bélen
B
Instituto de Biomédicina, Caracas, Venezuela.
Pérez Schael
Irene
I
Linhares
Alexandre C
AC
Ruiz Palacios
Guillermo M
GM
Guerrero
M Lourdes
ML
Yarzábal
Juan Pablo
JP
Cervantes
Yolanda
Y
Costa Clemens
SueAnn
S
Damaso
Silvia
S
Hardt
Karin
K
De Vos
Béatrice
B
D000284:Administration, Oral; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology*; D002675:Child, Preschool; D016001:Confidence Intervals; D003968:Diarrhea, Infantile / Q000517:prevention & control / Q000821:virology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D007843:Latin America; D008297:Male; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000914:Antibodies, Viral; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated