[e-drug] New vaccines to fight killer rotavirus

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: New vaccines to fight killer rotavirus
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["608 000 people die from rotavirus gastroenteritis every year, 80% of whom are in developing countries. 39% of diarrhoea deaths are now attributed to rotavirus." So what about a vaccine?
>From the Lancet Infectious Diseases, http://infection.thelancet.com/journal/vol4/iss11/full/laid.4.11.newsdesk.31028.1
Copied as fair use; WB]

New vaccines to fight killer rotavirus

Dorothy Bonn 

The withdrawal of the world's first rotavirus vaccine, RotaShield, in 1999within 1 year of its approvalwas a devastating blow to all those involved in the fight against the deadly virus. According to Roger Glass, of the Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA), however, this setback has given a new impetus to the development of alternative rotavirus vaccines. The driving force is the enormous mortality from rotavirus diarrhoea, he says. We have several million children dying for lack of vaccine.

Rotavirus hits children everywhere, irrespective of standards of hygiene and sanitation. Only an effective vaccine will protect against the infection, says CDC's Umesh Parashar. He estimates that almost all children are infected by age 5 years, with a peak incidence of clinical illness at 436 months, and that 608 000 people die from rotavirus gastroenteritis every year, 80% of whom are in developing countries. 39% of diarrhoea deaths are now attributed to rotavirus.

Two new (live oral) rotavirus vaccinesthe first since RotaShield was withdrawnare finally to be launched. GlaxoSmithKline's (GSK) Rotarix will be introduced in Mexico before the end of 2004, Merck's RotaTeq in the USA in 2005. Each has been proved in trials of around 70 000 babies. The new strategy of investigating these vaccines in developing countries, not just the USA and Europe, should speed up delivery of the vaccines to poorer countries, where they are most needed. If RotaShield had been assessed in this way, Glass suggests, it might not have been withdrawn, because the benefits of reduced death rates in developing countries would have been shown to outweigh by far the very small risk of intussusception (the reason for its withdrawal). This missed opportunity turned out to be even more unfortunate when a reappraisal of RotaShield by scientists at the US National Institutes of Health (NIH) found no overall excess risk of intussusception, a slight excess only in infants given the first dose of vaccine at age 37 months, and no intussusception in infants vaccinated at younger than 60 days of age. We now recommend starting rotavirus vaccination at 04 weeks of age, with a second dose at 48 weeks, says Albert Kapikian (NIH). This schedule has the potential to eliminate the risk of intussusception after any rotavirus vaccine.

The overall effectiveness of the new vaccines has not been fully assessed. Rotarix contains only the G1 serotype, which accounts for just over half the rotavirus infections worldwide; but GSK claims it also provides 83% cross-protection against non-G1 strains. RotaTeq contains five serotypes (G1G4 and P1), which account for 75% of rotavirus strains around the world, but Merck is still assessing its effectiveness against other serotypes. We shall have to see how they perform against G9 in Asia, G8 in Africa, and G5 in Brazil, says Glass. One issue still to be addressed is how the vaccines will work in some of the poorest countries, where, says Glass, the effectiveness of other enteric vaccines (polio and cholera) is known to be compromised. The Rotavirus Vaccine Program (RVP), based in Seattle (WA, USA), is in discussion with GSK and Merck to investigate their rotavirus vaccines in this setting.

Several other rotavirus vaccines are in the pipeline. Neonatal rotavirus strains are being investigated as candidate vaccines in Australia and India. At the NIH, Kapikian is assessing a hexavalent (G1-4, G8, G9) vaccine. And the NIH has now licensed its tetravalent vaccine (formerly licensed as RotaShield) to biotech company BIOVIRx for global marketing. A vaccine based on rotavirus's VP4 spike protein could, says Philip Dormitzer (Harvard Medical School, Boston, MA, USA), who has analysed its structure, be inexpensive and stable without a cold chain, making it ideal for developing countries.

One worry with rotavirus is the possible emergence of new strains. Ruth Bishop (University of Melbourne, Australia), who discovered rotavirus as the major cause of childhood diarrhoea more than 30 years ago, is hopeful that the full range of human serotypes has now been identified, since no new ones have been discovered for several years. But Glass is less sanguine. G5, G8, and G9 all emerged in the 1990s, and all are becoming more common, he says. We don't know what surprises may still be in store for us.

Both Merck and GSK are negotiating to lower their prices for developing countries in exchange for guaranteed sales volumes. However, for the 75 poorest countries (where yearly incomes are less than $1000 a person) the most promising option is the Global Alliance for Vaccine and Immunization (GAVI), which has given rotavirus vaccination a top priority. But GAVI's success, says John Wecker of RVP, depends on the willingness of the global donor community to acknowledge the value of childhood vaccination through continued and growing financial contributions.