IDSA 2011: Successful Initial Results of a Malaria Vaccine Trial

BOSTON, MA—At a symposium on “Vaccines for a Global Community” at the annual meeting of the Infectious Diseases Society of America, Christian Loucq, MD, director of the PATH Malaria Vaccine Initiative, gave a presentation featuring successful initial results of an ongoing Phase 3 malaria vaccine trial. The results were also published online this week in the New England Journal of Medicine. (To listen to an interview HCPLive conducted with Loucq at the IDSA meeting, click here.)

The trial of the RTS,S experimental vaccine is being carried out in 11 centers in seven African countries. It includes participants divided into two age categories: those 6-12 weeks old at enrollment and those 5-17 months old. Each age category was divided up into three groups: those receiving all three doses of RTS,S at one-month intervals and scheduled to receive a booster dose 18 months after the third dose; those receiving the three vaccine doses without a booster dose; and a control group receiving a non-malaria vaccine.

In all, 15,460 participants were enrolled in the trial, including 6,537 in the 6-12-week-old category and 8,923 in the 5-17-month-old category. During 12 months of follow-up of the first 6,000 children enrolled in the older category, the incidence of clinical malaria was 0.44 per person-year among those who received the malaria vaccine and 0.83 per person-year in the control group, making the vaccine efficacy 55.8%. Of those in the older category who received the malaria vaccine, 2.0% experienced at least one episode of severe malaria, compared with 3.8% of those in the control group, for an efficacy of 47.3%.

Asked to explain why RTS,S has shown such promising results when researchers have tried and failed for decades to produce a viable malaria vaccine, Loucq told HCPLive: “The way the vaccine has been designed is very important. There is a proper selection of the antigen and there is a construct that is a virus-like particle, which is very important in terms of presenting the antigen to the immune system as well as the adjuvant, a proprietary adjuvant of [GlaxoSmithKline (GSK) Biologicals] that is definitely very, very important in inducing a high-quality immune response.”

In the older category, 17.6% of those who received the vaccine reported serious adverse events, compared with 21.6% of those in the control group. In both groups, 0.9% of the children died, and cause of death (where determined) was similar for both groups. Malaria accounted for very few of the deaths from either group—just 10 of 151 total deaths—which helps explain why the vaccine did not yield a reduced death rate.

At least one serious adverse event considered related to the vaccine occurred in 10 of 5,949 children in the older age category who received the malaria vaccine, compared with one of 2,974 older children in the control group. Meningitis was reported in 11 of the older children who received the vaccine compared with one child in the control group.

The level of protection for older children who received the malaria vaccine was lower at the end of the 12-month surveillance period than at the beginning, which contrasts with the findings of most of its Phase 2 studies. Upcoming reports on the trial include the results of the first 6,000 subjects in the 6-12-week-old category at the end of 2012 and final data at the end of 2014. Pending these results, the World Health Organization is likely to recommend the vaccine’s use in some African countries as early as 2015.

The ongoing trial was sponsored by GSK, the vaccine’s developer and manufacturer. It was paid for by GSK and the PATH Malaria Vaccine Initiative, which received a grant from the Bill and Melinda Gates Foundation. GSK has reportedly spent $300 million on development of the vaccine and the Gates Foundation $200 million.