Malaria vaccine protected against parasites similar to vaccine strain

Thera MA. N Eng J Med. 2011;365:1004-1013.

Issue: October 2011

Although the malaria vaccine did not provide significant protection against all clinical episodes of malaria, it did prevent clinical malaria caused by parasites that were similar to the vaccine strain, according to findings published in The New England Journal of Medicine.

“This is good news — it suggests that by picking the right few strains to include in the vaccine, just as was done for polio and flu vaccines, we might be able to design a much better malaria vaccine,” Christopher V. Plowe, MD, MPH, of the Howard Hughes Medical Institute, told Infectious Disease News.

According to background information in the study, previous findings have shown that the vaccine has immunogenicity and acceptable safety in adults and children from Mali, Africa. For this reason, Plowe and colleagues assessed the efficacy of the vaccine against clinical falciparum malaria in a double blind, randomized trial.

Between May 2007 and February 2008, 400 healthy children aged 1 to 6 years were randomly assigned to receive either the malaria vaccine or a control vaccine and followed for 6 months. Primary outcome measure was malaria, defined as fever and at least 2,500 parasites/mm³ of blood. Secondary outcome measure was malaria caused by parasites with the apical membrane antigen-1 (AMA1).

Compared with a 54.4% cumulative incidence of the primary endpoint in the control group, primary endpoint was 48.4% in the malaria-vaccine group. Efficacy against the primary endpoint was 17.4% (HR=0.83; 95% CI, 0.63-1.09); efficacy against the first and subsequent episodes of malaria was about 20%; and efficacy against the secondary endpoint was 64.3% (HR=0.36; 95% CI, 0.08-0.86).

Adverse events, including local reactions and fever after vaccination, were more frequent in those assigned the malaria vaccine.

“This is the first time that a blood-stage vaccine has shown any significant ability to protect against clinical malaria,” Plowe said. “Our study gives us hope that it should be possible to make a malaria vaccine that really prevents malaria illness.” – by Ashley DeNyse

Disclosure: This research was funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00460525.

The candidate malaria vaccine did not provide significant protection against clinical malaria. Relatively few infections with vaccine strain AMA1 parasites (n=22) were documented in this trial; however, the strain-specific protective efficacy observed in children who received the candidate vaccine was 64.3%. The authors hypothesize that the adjuvant (AS02_A) played a critical role in achieving these results because an earlier trial of a bivalent AMA1 vaccine with aluminum hydroxide as an adjuvant showed no overall or strain-specific efficacy. The findings indicate more is to be learned from AMA1, including how strain-specific monovalent vaccines might be combined to make a more protective multivalent malaria vaccine, and the benefit that might be achieved by using more immunogenic adjuvants. Investigations such as this study provide information useful to the eventual development of a malaria vaccine that will achieve the WHO Malaria Vaccine Technology Roadmap goal of providing more than 80% protective efficacy against clinical malaria for at least four years. To reach the long term goal of malaria elimination, a highly effective multi-stage and/or transmission-blocking vaccine will be essential.

– Meredith L. McMorrow, MD, MPH and Mary J. Hamel, MD

Both of CDC’s Malaria Branch, division of parasitic diseases and malaria

Disclosure: Drs. McMorrow and Hamel report no relevant financial disclosures.

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