New Oral, Live, Attenuated Human Rotavirus Vaccine Safe and Effective

August 10, 2007 — A new oral, live, attenuated human rotavirus vaccine (HRV) is safe, immunogenic, and highly effective in preventing rotavirus gastroenteritis in healthy Mexican infants, according to the results of a study reported in the August issue of Pediatrics.

"Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide," write Guillermo M. Ruiz-Palacios, MD, from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico, and colleagues. "The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied."

This randomized controlled trial took place from June 2001 through May 2003. In Mexico, 405 healthy infants were randomized to receive a vaccine at virus concentrations of 104.7, 105.2, or 105.8 infectious units, or to receive a placebo. At 2 and 4 months of age, infants received the vaccine or placebo along with a diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine.

To collect information regarding infant health, the investigators conducted weekly home visits after the infants received the first dose of the vaccine or placebo. During each episode of gastroenteritis, stool samples were collected and tested for rotavirus antigen and serotype. Monitoring continued to 2 years of age.

Compared with infants who received the placebo, those who received the vaccine had a higher rate of seroconversion. Efficacy after 2 oral doses of the vaccine was 80% against any rotavirus gastroenteritis and 95% against severe rotavirus gastroenteritis, when data were pooled from the vaccine groups.

At the highest virus concentration of 105.8 infectious units, efficacy of the vaccine was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause. In this cohort, the predominant serotype of infecting rotavirus was wild-type G1, which was present in 85% of cases.

The vaccine was well tolerated overall, and the vaccine and placebo groups had similar adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting.

"This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants," the authors write. "This vaccine produced comparable protection to natural infection."

Limitations of the study include a sample size that was too small to draw any conclusions regarding the risk for intussusceptions and the inability to determine the effect of the vaccine in preventing very severe gastroenteritis.

"The withdrawal of the first rotavirus vaccine, RotaShield (Wyeth Lederle Laboratories, Philadelphia, PA), taught important lessons and provided directions for the development of the next generation of rotavirus vaccines," the authors conclude. "A vaccine that may prevent 440,000 childhood deaths each year, or 1 in 20 deaths among children younger than 5 years, is now a reality and will become available sooner than ever anticipated in the developing world, where they are most needed.... Additional postmarketing evaluation of the HRV should continue to prove its safety so that it can be incorporated into routine infant immunization schedules and have a positive impact on the burden of this worldwide, life-threatening disease."

GlaxoSmithKline Biologicals sponsored this study and employs 3 of its authors.

Pediatrics. 2007;120:e253-e261.

Source: http://www.medscape.com/viewarticle/561231?sssdmh=dm1.293374&src=nldne