Volume 29-09
1 May 2003

[Table of Contents]

INTERNATIONAL NOTES

ROTAVIRUS VACCINES, AN UPDATE

In 1999, WHO published a position paper on rotavirus vaccines. However, for reasons described below, no rotavirus vaccine is currently available internationally. This note provides a brief update on recent developments in this field. As soon as new rotavirus vaccines have been licensed and become available on the international market, a fully revised position paper will be published in this journal.

Background

Rotavirus is the most common cause of severe diarrhoeal disease in infants and young children worldwide and an important public health problem, particularly in developing countries. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease.

Although several different groups and serotypes of rotavirus may cause disease, group A rotaviruses, which infect the young of both humans and animals, are the most important from a public health standpoint. Cross-reactivity occurs between some rotavirus antigens of different groups and serotypes. A child's first rotavirus infection apparently results in a serotype-specific immune response to capsid antigens (VP7 or G-antigens). This response is broadened by subsequent exposures and protects against later rotavirus infections with different serotypes. Rapid developmment of immunity following natural infection encouraged the development of rotavirus vaccines.

In August 1998, a tetravalent, rhesus-human reassortant rotavirus vaccine was licensed in the United States. This vaccine consists of VP7-serotype antigens (G1-G4) representing the most common human rotaviruses. After inclusion of this vaccine in the immunization schedule for infants in the USA, and immunization of almost 1 million individuals, several cases of vaccine-associated intussusception were reported. The period of greatest risk of intussusception was shown to be 3-10 days after the first of three oral doses. Although the true overall incidence of this adverse event proved difficult to assess, a group of international experts suggested a consensus rate of 1 per 10,000 vaccinated infants. The pathogenic mechanisms involved are currently unknown.

As a consequence of this rare but potentially dangerous adverse effect, the manufacturer withdrew the vaccine from the US market 9 months after its introduction. Although still licensed, the vaccine has not been tested since then or licensed in other parts of the world.

Different strategies for new rotavirus vaccines

A lamb rotavirus vaccine is licensed and used in China, but no rotavirus vaccines are currently available on the international market. Of the several candidate vaccines under development, only two have reached phase III trials.

A pentavalent vaccine based on a bovine rotavirus strain reassorted with the common VP7 and VP4 genes of human rotaviruses has been well tolerated in phase II and III studies and provided good protection both against severe rotavirus disease and against any rotavirus disease. This vaccine is currently undergoing large-scale safety trials to exclude any potential association with serious adverse events such as intussusception.

A monovalent human rotavirus vaccine candidate is now in phase II and phase III evaluation. It represents the most common of the human rotavirus VP7 and VP4 antigens. In early trials, this candidate vaccine showed high protective efficacy both against any rotavirus diarrhoea and against very severe rotavirus disease. Large-scale safety and efficacy trials are in progress in developing countries.

Other vaccine candidates under development include a human neonatal rotavirus strain and two human-bovine reassortant vaccines. Subunit rotavirus vaccines are also being investigated.

WHO position

WHO strongly recommends the rapid development of new and safe vaccine candidates against rotavirus disease and parallel evaluation of new candidates in developed and developing countries. WHO also encourages measures to establish the burden of rotavirus disease in developing countries in order to provide the necessary information for advocacy and risk-benefit analyses, the outcome of which may vary with the epidemiological and socioeconomic setting.

Source:    Weekly Epidemiological Record, Vol 78, No 1/2, 2003.

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