Experimental malaria vaccine promising
An experimental malaria vaccine protected 65% of Mozambique infants who received a full course of injections, paving the way for a large clinical trial of what could be the first vaccine against the deadly disease, researchers reported Wednesday.
Infants are among the most vulnerable to malaria. Immunization of infants has proved difficult for a variety of illnesses, including measles and pneumococcal disease.
The findings “show that we are making real progress toward a malaria vaccine,” said Dr. Christian Loucq, director of the PATH Malaria Vaccine Initiative, which sponsored the trial with funding from the Bill & Melinda Gates Foundation.
Loucq said he thought the vaccine could be commercially available by 2012.
The results, published online in the journal Lancet, were reported Wednesday at a Seattle malaria meeting sponsored by the Gates Foundation.
Malaria kills more than 1 million people each year, 90% of them in sub-Saharan Africa and 80% of them younger than 5. It makes 300 million people seriously ill.
Substantial progress in treating and preventing the disease is being made, according to a UNICEF report issued Tuesday at the Seattle meeting. The use of insecticide-treated bed nets has grown sharply in sub-Saharan Africa, and all countries there have adopted artemisinin-based drug therapy, the most effective treatment for the disease, the report said.
Experts hope a malaria vaccine would have an even greater effect, but developing one has proved extremely difficult because of the complicated life cycle of the mosquito-borne Plasmodium parasites that cause the disease.
The cycle begins when infected mosquitoes bite humans, injecting them with a form of the parasite called a sporozoite. The sporozoites invade the liver and begin reproducing in a new form called merozoites.
Some merozoites can remain dormant in the liver for years, but most escape into the bloodstream and infect red blood cells, where they continue to replicate. Eventually, the blood cells burst, releasing more of the parasites into the bloodstream.
The parasites are then ingested by mosquitoes when they bite an infected human. They reproduce in the mosquito’s gut and the cycle begins again when the mosquito bites an uninfected person.
It has proved exceptionally difficult to find a vaccine that can disrupt this complicated history, and several once-promising vaccines have fallen by the wayside because of poor results in field trials.
The new vaccine, called RTS,S/AS02A, or Mosquirix, was developed by GlaxoSmithKline Biologicals. It uses two genetically engineered proteins from the surface of the Plasmodium sporozoites. The finished vaccine also contains a combination of non-biological materials that stimulate the immune system to react more strongly to the proteins.
Dr. Pedro Alonso of the University of Barcelona, who led the current study, reported in 2004 on a trial of the vaccine in more than 2,000 children, ages 1 through 4. During the first six months of the trial, those receiving the vaccine had about 30% fewer episodes of malaria and 59% fewer episodes of severe malaria.
At a news conference Tuesday, Alonso said the children’s blood still contained high levels of antibodies against the parasite four years after inoculation.
In the new trial, Alonso and his colleagues studied 214 infants at the Manhica Health Research Center in rural southern Mozambique, an area with a high malaria infection rate. Half the infants received doses of the vaccine at ages 10, 14 and 18 weeks. A control group received a hepatitis B vaccine.
All the families received insecticide-treated sleeping nets, and their homes were sprayed with insecticide twice during the study.
The study was designed primarily to assess safety, and the team found no adverse effects from the vaccine.
Infants who received the full three doses of vaccine had 65% fewer new infections and clinical illnesses in the three months after the last dose was given than did those in the control group.
Some children contracted malaria before all three doses could be given. Nonetheless, among all children who received at least one dose of the vaccine, clinical illness was reduced by 35% over the first six months of the study.
The results are important, Alonso said, because “children under 1 year of age carry a large and disproportionate burden of infections” and tend to have a more serious illness when they are infected.
Dr. W. Ripley Ballou, a Glaxo- SmithKline vice president, said the company had spent $300 million to develop the vaccine and would invest an additional $50 million to $100 million to bring it to market. That is in addition to the $107 million provided by the Gates Foundation for the clinical trials.
The larger clinical trial will begin next year with 16,000 children in seven African countries. Two-thirds of them will receive the vaccine at ages 5 to 17 months, while the rest will receive it shortly after birth as part of routine pediatric immunizations.
Ballou would not say how much the vaccine would cost.