May 17, 2016

Experimental malaria vaccine protects adults for more than a year

At a Glance

  • An experimental malaria vaccine protected healthy adults from infection for more than a year after immunization.
  • The vaccine is now being tested in larger trials.
Malaria sporozoites Malaria sporozoites, the infectious form of the malaria parasite that is injected into people by mosquitoes. NIAID

Malaria is caused by the Plasmodium falciparum parasite, which is transmitted to people through mosquitoes. Improved prevention and control efforts have helped to curb malaria’s impact worldwide. However, roughly half of the world’s population continues to be at risk for malaria. In 2015, about 214 million new malaria cases and 438,000 deaths occurred—largely among African children under the age of 5.

Researchers have been working to develop a vaccine that provides long-term, reliable protection from malaria. An effective vaccine could protect people living in malaria-endemic regions as well as travelers and military personnel.

The experimental PfSPZ Vaccine was developed and produced by Sanaria Inc., of Rockville, Maryland, with support from NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The vaccine is made of live but weakened P. falciparum sporozoites—the early developmental form of a malaria-causing parasite. Previous research by NIAID investigators showed the PfSPZ Vaccine to be highly protective 3 weeks after immunization. In their latest trial, NIAID researchers led by Dr. Robert A. Seder and collaborators at the University of Maryland School of Medicine assessed if protection could last for longer periods. The study appeared online on May 9, 2016, in Nature Medicine.

The Phase 1 trial took place at the NIH Clinical Center in Bethesda, Maryland, and at the University of Maryland Medical Center. The team enrolled healthy adults, ages 18 to 45, who had never had malaria. The researchers separated the participants into small groups to test different conditions. A total of 57 volunteers received the PfSPZ Vaccine and 32 served as unvaccinated controls.

To determine if the number of immunizations influenced protection, groups of participants received either 3 or 4 intravenous (IV) immunizations at a higher dose than previously tested. To compare different routes of administration, one group received 4 intramuscular injections (IM) of the vaccine at a dose about 10-fold higher than the IV dose. 

To assess short-term protection, participants were exposed to the bites of infected mosquitoes 3 weeks after their final vaccination. Researchers then took blood samples to measure parasite levels. Of the 9 participants who received 3 IV doses, 3 had no detectable parasites in their blood. Of the 9 who received 4 IV doses, 7 had no detectable parasites. Of the 8 participants who received 4 IM doses, only 3 were protected. These results show that 4 IV doses of the vaccine confer more protection than 3 doses, and that IM immunization isn't highly effective.

To assess long-term protection, another group of participants was given 4 IV doses of the vaccine and exposed to the bites of infected mosquitoes at 21-25 weeks. Six of the 11 participants had no detectable parasites in their blood after this exposure. Finally, 5 of the people who’d been protected by 4 IV doses were exposed to mosquito bites again at 59 weeks. None developed parasites in their blood. These results provide the first evidence that long-term protection can be achieved with this vaccine.

No serious adverse events were attributed to vaccination. Since protection appeared to correlate with vaccine dose, the team is now testing higher doses of the vaccine in larger, longer trials. One important question is whether the PfSPZ Vaccine can protect against other circulating P. falciparum strains.

“A malaria vaccine that provides long-term protection is urgently needed to reduce mortality and eliminate transmission,” says NIAID Director Dr. Anthony S. Fauci. “This study is an encouraging step forward in our goal to control and ultimately eradicate malaria.”

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Reference: Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Ishizuka AS, Lyke KE, DeZure A, Berry AA, Richie TL, Mendoza FH, Enama ME, Gordon IJ, Chang LJ, Sarwar UN, Zephir KL, Holman LA, James ER, Billingsley PF, Gunasekera A, Chakravarty S, Manoj A, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, K C N, Murshedkar T, DeCederfelt H, Plummer SH, Hendel CS, Novik L, Costner PJ, Saunders JG, Laurens MB, Plowe CV, Flynn B, Whalen WR, Todd JP, Noor J, Rao S, Sierra-Davidson K, Lynn GM, Epstein JE, Kemp MA, Fahle GA, Mikolajczak SA, Fishbaugher M, Sack BK, Kappe SH, Davidson SA, Garver LS, Björkström NK, Nason MC, Graham BS, Roederer M, Sim BK, Hoffman SL, Ledgerwood JE, Seder RA. Nat Med. 2016 May 9. doi: 10.1038/nm.4110. [Epub ahead of print]. PMID: 27158907.

Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Clinical Center (CC).