Vaccination has a vital role to play in reducing the global malaria burden, but more research is needed into the vaccine’s mechanism of action, according to a recently-published study and accompanying editorial in the journal Clinical Infectious Diseases. 1,2 

The first effective vaccine against a parasite, the RTS/S vaccine, developed by GlaxoSmithKline and the Malaria Vaccine Initiative, has shown a 30-50% efficacy rate, according to several studies.3-5 While this is an advance in the fight against malaria, this efficacy rate is much lower than vaccines used against other illnesses. The vaccine’s exact mechanism that results in this level of effectiveness has not been fully understood and is still under investigation, but a recently-published study by Vashti Irani and colleagues at the Burnet Institute in Melbourne, Australia has found that malaria vaccine efficacy involves the erythrocyte-binding antigen 175 (EBA-175).

Studies like Ms Irani’s and research into other ways to prevent malaria are important, said Chandy C John, MD, of the Ryan White Center for Pediatric Infectious Disease and Global Health at the Indiana University School of Medicine, because: “almost 200 million people a year develop malaria. It kills almost 600,000 people [many of whom are children in Africa], and even those who survive often have long-term effects like anemia, behavioral problems, and a decrease in cognitive ability. Malaria can also make you more vulnerable to other infections.”


Continue Reading

In the past decade, malaria funding has increased dramatically, mainly from sources like Bill and Melinda Gates Foundation, and malaria eradication is one of the Foundation’s goals. Although major gains have been reported in controlling the disease and slowing the importation of malaria into areas like the United States, the main ways to reduce the number of malaria cases to zero, according to Dr John, is continued research into the mechanisms of action of malaria vaccines, along with the implementation of novel preventive approaches.

Vaccine Study

Ms Irani’s study followed 206 children ages 5-14 from Papua New Guinea who had been exposed to malaria. Study participants were first given artesunate for 7 days to clear parasitemia. Researchers took demographic data and blood samples every 2 weeks for 6 months to check for evidence of asymptomatic reinfection, and noted that, over 6 months, 95.3% of children were reinfected with Plasmodium falciparum and 39.3% of those developed clinical disease.1

The researchers concluded that naturally-acquired binding-inhibitory antibodies played an important role in protecting the children from malaria and this, “further supports the potential of EBA-175 as a vaccine.”1 

More research is needed to confirm the findings, but in an interview with Infectious Disease Advisor, Dr John explained that, “studies like these broaden our fundamental understanding of how clinical and biological immunity develops in malaria, and this broadened understanding should lead, in the long run, to development of better malaria vaccines.”2

He added that the study”describes a new way of testing for functional immunity to the malaria parasite — that is, looking not just at antibodies to the parasite, but antibodies that inhibit binding of the parasite to the red cell, which would prevent the parasite from getting into the red cell. Malaria parasites live in red cells, so this effectively prevents or decreases their ability to multiply in humans.” For clinicians, Dr John says that, “studies like this are important, because they give us better ways of assessing how the human immune system protects against malaria, and we can use these insights to design better vaccines.”

Novel Approaches to Malaria Control and Prevention

In addition to vaccination development, mosquito control is essential to preventing malaria. Dr John noted in an editorial commentary that accompanied Ms Irani’s study that bed nets treated with insecticides and indoor spraying are important to combat malaria.2 Another promising technique in development involves genetically modifying mosquitoes to create a hostile environment for the parasite.2  However, the full ramifications of genetically modifying mosquitoes remains unknown. 

Antimalarial therapy and comprehensive drug administration are also vital disease interventions, but like insecticides, drug resistance is a concern, according to Dr John’s commentary. He warns that these methods could be ineffective if used individually in areas where malaria is widespread. 

References

1. Vashti I, Ramsland PA,  Guy AJ et al. Acquisition of functional antibodies that block the binding of erythrocyte-binding antigen 175 and protection against Plasmodium falciparum malaria in children. Clin Infect Dis. 2015;61(8):1244-52.

2. John CC. Toward a better malaria vaccine: understanding how antibodies to malaria protect against disease. Clin Infect Dis. 2015;61(8):1253-54.

3. Agnandji ST,  Lell B,  Soulanoudjingar SS et al First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011;365:1863–75.

4. RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 2014; DOI: 10.1371/journal.pmed.1001685

5. RTS,S Clinical Trials Partnership, Agnandji ST, Lell B et al. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med.2012367:2284-2295