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Safety, immunogenicity and efficacy in healthy infants of G1 and G2 human reassortant rotavirus vaccine in a new stabilizer/buffer liquid formulation

CLARK, H. FRED DVM, PhD; BURKE, CARL J. PhD; VOLKIN, DAVID B. PhD; OFFIT, PAUL MD; WARD, RICHARD L. PhD; BRESEE, JOSEPH S. MD, MPH; DENNEHY, PENELOPE MD; GOOCH, W. MANFRED MD; MALACAMAN, EDGARDO MD; MATSON, DAVID MD, PhD; WALTER, EMMANUEL MD, MPH; WATSON, BARBARA MD; KRAH, DAVID L. PhD; DALLAS, MICHAEL J. PhD; SCHÖDEL, FLORIAN MD; KAPLAN, KAREN M. MD; HEATON, PENNY MD

Pediatric Infectious Disease Journal: October 2003 - Volume 22 - Issue 10 - pp 914-920
Original Studies

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 ∼2 to 4 months of age were enrolled at 19 US sites to receive 3 HRRV or placebo doses ∼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 (≥38.1°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 ≥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.

From the University of Pennsylvania School of Medicine (HFC, PO) and the Philadelphia Department of Public Health (BW), Philadelphia, PA; Merck & Co., Inc., West Point, PA (CJB, DBV, DLK, MJD, FS, KMK, PH); Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (RLW); Centers for Disease Control and Prevention, Atlanta, GA (JSB); Brown Medical School, Providence, RI (PD); Medical Research Associates of Utah, Inc., Salt Lake City, UT (WMG); Canton Pediatrics, Inc., Canton, OH (EM); Center for Pediatric Research, Norfolk, VA (DM); and Duke University Medical Center, Durham, NC (EW).

Accepted for publication July 21, 2003.

Presented in part at the 42nd Interscience Conference on Antimicrobials and Chemotherapy. 30

Reprints not available.

© 2003 Lippincott Williams & Wilkins, Inc.