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Dr. Stowers and Louis Miller, from NIAID and Genzyme Transgenics
Corporation, joined to produce two transgenic mouse strains. Each strain carried a form
of the gene for a surface protein from the deadliest malaria parasite, Plasmodium
falciparum. The researchers designed the transgenes to be switched on by the cells that
line the mammary glands, such that the resulting proteins would be secreted into the
animals' milk.
Both mouse strains produced large quantities of the desired vaccine protein. When
used to vaccinate monkeys, one of the proteins protected the animals against malaria:
only one of five immunized monkeys contracted the disease. By comparison, six out of
seven unvaccinated animals had to be treated for virulent malaria.
The high yield of the protein and its ability to stimulate protective immunity in
mice offers promising evidence that the technique could also be used in goats or even
cows. The researchers had anticipated future studies in goats by designing the transgenes'
on/off switch using regulatory elements from goat DNA.
Transgenic Goat's Milk Offers Hope for Tackling Children's Intestinal Disease
Lysozyme is a protein found in the tears, saliva and milk of all mammals. It is
found at high levels in human breast milk, however goat's milk contains only 0.06
percent as much lysozyme as does human milk. Lysozyme inhibits the growth of bacteria
by destroying the bacterial cell wall, causing the contents of the cell to leak out.
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Because lysozyme limits the growth of bacteria that cause intestinal infections and
diarrhea, and encourages the growth of beneficial intestinal bacteria, lysozyme is
considered to be one of the main components of human milk that contribute to the health
and well-being of breast-fed infants.
For more than a decade, UC Davis researchers have been looking for ways to
enrich the milk of cows and goats with some of the beneficial compounds like lysozyme
that are found in human breast milk. About eight years ago, they used gene-transfer
technology to develop a line of transgenic dairy goats that carry the gene for human
lysozyme and, consequently, produce human lysozyme in their milk.
The rotavirus is the main cause of viral gastroenteritis in young children and leads
to 500,000 deaths per year worldwide, particularly in developing countries. A vaccine,
made from a live attenuated virus was available but was taken off the market several
years ago because it was linked to the risk of intussusceptions for unknown reasons.
Researchers at BioProtein Technologies therefore took another approach already
validated by INRA laboratories that consists of developing a recombinant vaccine. This
type of vaccine is actually not designed from an attenuated virus but, instead, by
separating the proteins that induce the immune response (antigens) from the rest of the
virus and using only these antigens for the vaccine.
They chose two viral surface proteins that form a complex in vitro when co-
expressed, that imitates the structure of the virus capsid. This protein complex, which
has absolutely no infecting power whatsoever, proved itself to be effective on different
animal models for immunisation against the entire virus. On the other hand, the means for
synthesizing these proteins on a large scale are limited, very costly and not compatible
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with industrial development. Researchers at BioProtein Technologies and at INRA
developed transgenic animals capable of synthesizing these proteins. By modifying the
genome of female rabbits, they were able to have them secrete recombinant viral protein
in their milk. The patent for the process was issued on 21st September 2005. Proteins
produced in this way were tested on mouse models. After vaccination, the mice are
protected against infection by the virus.