Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation.
BACKGROUND
A refrigerator-stable rotavirus (RV) vaccine that withstands gastric acid is anticipated to permit more widespread use of RV vaccine.


OBJECTIVE
We investigated for the first time in infants an oral, liquid formulation of G1 and G2 human bovine reassortant rotavirus vaccine (HRRV) with a new stabilizer/buffer (S/B) containing sucrose, sodium phosphate and sodium citrate.


METHODS
During 1997 through 1998, 731 healthy infants approximately 2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses approximately 6 to 8 weeks apart in a partially double blinded study. Infants were randomized to: (1) HRRV with no S/B but with prefeeding; (2) HRRV plus 1 of 3 different concentrations/volumes of S/B; or (3) placebo.


RESULTS
No serious vaccine-related adverse experiences or intussusception cases were reported. No statistically significant differences were observed between vaccine and placebo recipients for fever (> or =38.1 degrees C) 0 to 7 days after any dose, irritability, vomiting or diarrhea incidence 0 to 42 days after any dose. Vaccine virus shedding among vaccine recipients was uncommon. Among S/B vaccine groups, proportions of infants with a > or =3-fold titer rise from baseline to Postdose 3 for G1 serum-neutralizing antibody (SNA), G2 SNA, WC3 SNA, serum anti-RV IgA, serum anti-RV IgG and stool anti-RV IgA were generally similar to those of the prefed non-S/B group.


CONCLUSIONS
HRRV with a new S/B was generally well-tolerated; immunogenicity was generally similar to the prefed non-S/B group. No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV.
Clark
H Fred
HF
University of Pennsylvania School of Medicine, Philadelphia, USA.
Burke
Carl J
CJ
Volkin
David B
DB
Offit
Paul
P
Ward
Richard L
RL
Bresee
Joseph S
JS
Dennehy
Penelope
P
Gooch
W Manfred
WM
Malacaman
Edgardo
E
Matson
David
D
Walter
Emmanuel
E
Watson
Barbara
B
Krah
David L
DL
Dallas
Michael J
MJ
Schödel
Florian
F
Kaplan
karen M
kM
Heaton
Penny
P
D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D004311:Double-Blind Method; D005243:Feces / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007109:Immunity / Q000502:physiology; D007223:Infant; D008297:Male; D012016:Reference Values; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012449:Safety; D012680:Sensitivity and Specificity; D014613:Vaccines, Attenuated / Q000008:administration & dosage
D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated