September 10, 2001
injects new life into vaccine program
The Bill & Melinda Gates Foundation has awarded a three-year, $885,000
subcontract grant to the lab of Harriet Robinson in support of her ongoing
research to develop a DNA-based vaccine for measles.
The grant is the first substantial funding for Robinsons measles
vaccine program, which is being conducted in collaboration with Diane
Griffin of Johns Hopkins University and Paul Rota of the Centers for Disease
Control and Prevention.
The Gates funding comes on the heels of a World Health Organization campaign,
launched this spring, to halve the number of measles deaths by the year
2005. A highly contagious virus spread through respiratory droplets, measles
accounts for some 900,000 of the estimated 1.6 million annual deaths worldwide
due to childhood vaccine-preventable diseases.
Despite widespread inoculation programs, measles remains endemic in many
developing counties. The vaccine usually is administered to children at
15 months of age. If given before that time, the temporary immunity conferred
to the child by maternal antibody blocks the vaccines ability to
raise protective immunity in the child. Unfortunately, children in many
developing countries either receive the vaccine too early or not at all.
The presence of maternal antibody is one of the biggest problems
for childhood vaccination programs not just against measles, said
Robinson, chief of microbiology and immunology at Yerkes. The immaturity
of the neonatal immune system also makes it challenging to develop effective
vaccines for infants.
The WHO believes that at last 90 percent of children must be vaccinated
to reduce measles deaths in developing countries. To that end, it views
as crucial the development of a vaccine that can work in the presence
of maternal antibody.
Following the DNA model that has shown promise in the development of
an AIDS vaccine, Robinson has been testing a measles vaccine developed
from the genes for the hemagglutinin and fusion proteinstwo surface
components of the measles virus. The vaccine regimen consists of an initial
shot to prime the immune system followed by a booster.
In its current form, Robinsons DNA vaccine has not raised antibody
in the presence of the maternal antibody. Robinson suspects that this
phenomenon may result from the interface between the measles antigen and
how the immune system recognizes that antigen in the presence of antibody.
If we can manipulate the measles antigen so that they will raise
antibody in the presence of maternal antibody, it will be a tremendous
boon for the development of vaccines for the first year of life,
Robinson plans to focus on refining the vaccine to further improve antibody
response and reduce the dosing regiment to one injection.
Rhesus monkeys are the only animal model available for studying measles.
The pathogenesis of the virus is remarkably similar in both macaques and
people. Because of its virulence and potential threat to the larger colony,
all monkeys enrolled in the measles vaccine program are vaccinated at
Yerkes and the transferred to JHU, where they are challenged with the
virus. At Johns Hopkins, Griffin also is conducting a parallel study on
the pathogenesis of the virus.
Measles vaccines based on both killed and live virus have existed since the early 1960s. Typically given as part of the MMR regimen that includes vaccines for mumps and rubella, the vaccine has successfully reduced incidence of the disease in the United States to less than 500 cases per year.
Although healthy children typically survive the infection, the mortality
rate for those in developing regions of the world, especially in sub-Saharan
Africa, can be as high as 25 percent because of malnutrition. The disease
also produces many complications. Among African children, it is a leading
cause of blindness and mental retardation.
With the most recent grant to Robinson, the Gates Foundation is now funding more than $1.6 million in vaccine research at Yerkes, including nearly $790,000 for malaria vaccine development.