Q & A: Researchers close in on malaria vaccine

Michael Good made the switch from doctor to scientific researcher because he couldn’t stand to watch any more babies die.

“I can be a doctor and treat sick children — and that’s honorable,” he said to himself. “But if I can develop science that can save millions of children, how much more valuable would that be?”

Now, as the developer of a promising new malaria vaccine, he’s poised to do just that. Malaria, a disease caused by parasites transmitted through the bites of infected mosquitos, kills an estimated 660,000 children a year, according to the World Health Organization. In Africa, a child dies of malaria every minute.

“For children, it’s probably the number one public health issue,” said Good, an immunologist at Griffith University in Queensland, Australia.

Scientists have been trying — unsuccessfully — to develop a vaccine to protect against malaria since the 1920s. There was a flash of hope in 2011 when early trials of a vaccine developed by GlaxoSmithKline showed promise. But a study published earlier this year showed the vaccine, which was only 40 percent effective to start with, provided less and less protection over time. Four years after inoculation, scientists found, the effect of the vaccine had completely dissipated.

Typically, a vaccine works by introducing a killed or weakened form of the bug it’s meant to protect against, which prompts the body to produce antibodies. Then, when a child encounters an active form of the disease, the body is ready and can respond faster and stronger. A malaria vaccine has eluded scientists largely because the malaria parasite, which has several radically different forms, constantly mutates its outer protein coat, Good said. Antibodies trained to recognize the protein coat can’t keep up as it as it changes.

It’s early still, but initial results from tests conducted on mice show Good’s vaccine induces long-lived immunity that transcends strain and species. GlobalPost sat down with Good to talk about his hopes — and fears — as he prepares to start human trials.

Q: You took a different approach to the vaccine than others before you. How does your vaccine work?

A: Our approach hasn't been to use individual proteins, but to use the whole parasite. The whole parasite contains thousands of proteins. … When you take the whole thing, there is almost certainty that there will be certain proteins that haven't changed. You only have to recognize the ones that haven't changed. It increases the probability that the vaccine will work.

We also found a way to induce what are called T cells to kill the parasite, as opposed to antibodies. Antibodies are small molecules that float around in the blood stream, recognize foreign germs and try to destroy them. T-cells, one of the white bloods cells of the body, would typically kill a cell of the body that's infected by a virus or kill a tumor cell.

It’s been known for some time that T cells can also kill malaria parasites, but no one had worked out a way to transform that idea into an effective vaccine strategy. The advantage of working with T cells is that T cells don't just recognize the surface of an organism like an antibody does. They recognize any protein within the parasite — even inside the parasite. Those proteins inside the parasite don't change, or change very little from one organism to another, whereas the proteins on the surface — the ones that are recognized by the antibodies — they do change from one parasite to another. We worked out a way to induce that population of T cells in a vaccine strategy. Those T cells, at least in our mouse model, have proven to be very effective in killing multiple strains of the parasite.

Q: What's been encouraging about what you've found so far?

A: Clearly, the things that will be critical in the human study are:

1) Does it work at all?
2) If it does work, does it protect against different strains of malaria?
3) How long does that protection last?

In the mice, we've answered those questions. The vaccine not only recognizes different strains, but also different species, which is very exciting to us.

Q: What are the potential weaknesses or limitations?

A: The vaccine has to be delivered into the body inside red blood cells. There are no other vaccines on the market today that use human cells as part of the vaccine. Measles, mumps, rubella — not one of these vaccines has human cells.

I don't think it's a huge problem in terms of production, because I don't think we'll need very many parasites in the vaccine. But it may raise cultural issues with some people not wanting to receive a vaccine containing human blood cells. It's more of a — I wouldn't call it a “yuck” factor — but people would have to get their heads around the idea. If the vaccine works, they'll have to accept it if they want to be protected against malaria.

Q: If the vaccine works, how easily could it be scaled up?

A: A vaccine that isn't simple to make, isn't cheap or cost effective won't get used. We were very cognizant of that fact from the beginning. We will be growing the vaccine here at the university for the first human studies. If we get success in our phase one study, our goal is to translocate this technology to one of the African countries where we are collaborating now. We want to get the vaccine manufactured there. I think if you want to get this to places of the world which need it most, you need local scientists and doctors to be very much part of the team.