No. 5, March 1989
The epidemiological features of rotavirus diarrhoea that are of greatest
relevance to vaccine development are as follows:
There are four serotypes of rotaviruses, designated 1 to 4. While they
all cause disease, serotype 1 appears to be the most common cause of epidemic
rotavirus diarrhoea in countries with a temperate climate. Information
on the distribution of rotavirus according to serotype in the developing
countries is limited.
Rotavirus is the major cause of severe dehydrating diarrhoea in young children
in both developed and developing countries.
This organism is responsible for 40-60% of the diarrhoea cases requiring
hospitalization in developed countries.
It accounts for 20-40% of severe diarrhoeas among children in the developing
Rotavirus diarrhoea is most common in children 6-24 months of age.
Potential rotavirus vaccines
It has been estimated that an effective rotavirus vaccine could:
Efforts to develop live attenuated, oral vaccines for human rotavirus diarrhoea
have resulted in five candidates: bovine, rhesus, bovine-human reassortant,
rhesus-human reassortant, and nursery strain vaccines. The bovine vaccines
(RIT 4237 and WC3) and rhesus vaccine (RRV-1) have been developed from
animal rotaviruses that are adapted to tissue culture. Bovine- human and
rhesus-human vaccines are genetically engineered, human-animal hybrid rotaviruses,
in which a surface protein of a human rotavirus has been incorporated into
an animal host virus. The nursery strain vaccine is a naturally attenuated
reduce all diarrhoeal deaths by 30% in the age group 6-24 months, and
avert 500 000 - 1 000 000 deaths in children annually.
Efficacy trials of rotavirus vaccines
Bovine rotavirus vaccines: The RIT 4237 strain of bovine rotavirus
was found to lack significant immunogenicity and efficacy in several trials
in developed and developing countries; it has been withdrawn by the manufacturer.
Evaluations of WC3 are under way in the Central African Republic and Israel,
and other trials are planned.
Rhesus rotavirus vaccines: A trial in Sweden showed high efficacy;
however, the vaccine caused fever in 79% of the children. High efficacy,
but with fewer side effects, was also found in a study in Venezuela where
there was a high prevalence of cases due to serotype 3, with which RRV-1
is closely related. In other studies in which serotype 1 was the most common
cause of rotavirus diarrhoea, the vaccine was not as efficacious.
Bovine-human and rhesus-human reassortant rotavirus vaccines:
According to the preliminary results of efficacy studies, a rhesus-human
serotype 1 reassortant apparently confers a high degree of protection against
serotype 1 disease. A combined rhesus-human reassortant rotavirus vaccine
has been prepared by mixing together the rhesus-human viruses for serotypes
1, 2 and 4, and the rhesus rotavirus (for serotype 3). A potential problem
with a combined vaccine is that the components may interfere with each
other, resulting in poorer responses to the individual serotypes than would
be observed after vaccination with single-serotype vaccines. Better immune
responses may be achieved by giving multiple doses or by increasing the
amount of virus in each dose. The vaccine is being tested for efficacy
in Peru and the USA.
Nursery strain vaccines: The candidate vaccine M37 is currently
being tested for safety and immunogenicity in volunteers. The rationale
for using a naturally attenuated human rotavirus as a vaccine is based
on observations that such "nursery strains" frequently infect neonates
in maternity wards without causing illness, and the infected infants are
later protected, at least in part, against diarrhoea caused by fully virulent
Research priorities of the WHO Diarrhoeal Diseases Control (CDD) Programme
The CDD Programme regards the development of an effective rotavirus vaccine
as a high priority, and is continuing to support efficacy trials of potential
vaccines in developing countries. Ideally, the vaccine should:
It is possible that, whatever the vaccine, multiple doses will be required
for maximum efficacy. In such case, it would be important to be able to
give rotavirus vaccine simultaneously with oral poliovirus vaccine (OPV)
in national expanded programmes on immunization (EPI).
induce substantial, long-lasting protection against rotavirus diarrhoea
in young children following a single oral dose, and
be administered at the age of 2-3 months (although the disease is most
severe in agegroup 6-24 months, some cases occur in much younger infants
in the developing countries).
The CDD Programme is also providing support to research on other approaches
to develop rotavirus vaccines, including genetically-engineered vaccines.
At present, however, the conventional methods described above appear more
likely to result in practical vaccines against rotavirus in the near future.
For further information, contact:
The Director, Division of Diarrhoeal and Acute Respiratory Disease
World Health Organization, 1211 Geneva 27, Switzerland
Tel: +41 22 791-2632, Fax: +41 22 791-4853,