WHEN a baby leaves the cocoon of its mother's womb, it faces a world of potential pathogens. Now, a model of the immature immune system - the first of its kind - promises to boost the development of vaccines designed specifically for newborns. There are very few such vaccines at present.
Around 1 million newborns, mainly in Asia and Africa, die every year from preventable infectious diseases, according to the World Health Organization. The best way to protect these children would be to vaccinate at birth, says Guzman Sanchez-Schmitz of Harvard Medical School and the Boston Children's Hospital in Massachusetts. "These kids are seen by health professionals at birth, but not again," he says.
"A lot of infections happen early in life," says Ofer Levy, an immunologist who works with Sanchez-Schmitz in the same lab. So even if you do see the child again later on, "you've missed the boat".
Yet vaccines for newborns are lacking, Levy says. Most are developed for adults and adapted for younger people. "Vaccine development for newborns is very ad hoc these days," he says.
A baby's immune system is distinct from an adult's, and tends to mount a much weaker response to foreign material, including infectious agents. While this is vital in early life for coping with an onslaught of non-threatening bacteria, it also means that babies are more susceptible to some infections and don't respond as well to vaccines developed for adults. "Studies have shown that immunity wanes months after vaccination," says Levy.
To improve the development of vaccines for newborns, Levy, Sanchez-Schmitz and their colleagues have created a new way of modelling the newborn immune system.
The team first took blood from human umbilical veins and used it to culture two types of cells: those that make up blood-vessel walls and white blood cells, which are key drivers of the immune response. Team member Chad Stevens, also at the Boston Children's Hospital, was able to grow these cells in the collagen matrix that in the body forms their physical and biochemical support system - something that has not been done before - by finding the ideal conditions in which to mature the collagen. The system is topped off with newborn plasma - the liquid component of blood.
The model is the first artificial immune system to consist of entirely human components,and acts in a similar way to a real newborn's immune system, says Levy. His team watched as white blood cells passed through blood-vessel-wall cells and transformed into dendritic cells - which recognise foreign material and flag it as a target for other immune cells - just as they would when they come across a pathogen in the body.
In their latest experiment, the team found that the model responded to the BCG vaccine for tuberculosis in the same way that newborns have in clinical trials. "A single dose of BCG vaccine not only activates dendritic cells but enhances their ability to drive white-blood-cell proliferation and the generation of signalling molecules," just as it would in a newborn, says Levy. What's more, the model produced the same ratio of cells, says Sanchez-Schmitz, who presented the work at the American Association of Immunologists' annual meeting in Boston earlier this month.
The researchers reckon their model provides a reliable way to test vaccines before trialling them in newborns. "The aim is to do a clinical trial in a test tube," says Levy.
He and Sanchez-Schmitz are already using the model to develop new adjuvants - agents that are added to vaccines to boost their effect. "We are also working on a novel approach to an HIV vaccine," Levy says.
Paul Offit, a paediatrician and director of the Vaccine Education Center at the Children's Hospital of Philadelphia, Pennsylvania, points out that while the model will likely aid vaccine development, it won't replace clinical trials altogether. "It's a nice, helpful in vitro model to look at newborn immune responses, but you will ultimately have to test any vaccine in animals and eventually newborns," he says.
Sukumar Pal, an immunologist at the University of California, Irvine, hopes that the model will speed up vaccine development. "If I want to test 1000 vaccine candidates, I could use this system to do so in a very short period of time," he says, estimating it might cut his trials from eight weeks to just one. "The use of human collagen is very smart," Pal adds. "It's a wonderful model to test vaccines."
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