Clinical Trial in Indonesian Soldiers Deployed to Papua to Support Licensure of a Whole-Sporozoite Vaccine to Prevent P. falciparum and P. vivax Malaria
Abstract
Malaria, caused by a single-cell parasite called Plasmodium, is the #1 ranked infectious disease threat facing military personnel during deployment. The best method to protect military personnel against malaria would be a safe, well-tolerated, highly effective vaccine that blocks infection. Such a “fire and forget” prevention vaccine, administered before deployment, could eliminate the need for antimalaria measures in the field. However, no vaccine against malaria, or any parasitic infection, is licensed for use in any country. Military personnel rely instead on drugs taken during deployment that kill the malaria parasites, and bednets, insect repellants, and insecticide-impregnated uniforms that reduce exposure to the Anopheles mosquito responsible for transmission. The most effective drugs have to be taken every day if they are to work. The problem faced by the military and also by international travelers is that compliance with drugs is poor, due in part to frequent and sometimes debilitating side effects, and in part to the logistical difficulty of taking daily medications, especially during the complex and unpredictable conditions of combat. Therefore, antimalarial drugs, even if effective in controlled settings, have not met the need to safeguard military personnel or other travelers. Protective measures against the mosquito are less effective than drugs and encumber the user, especially in hot climates where long sleeves and repeated application of repellants are impractical, and bednets are difficult to transport and set up. Because the mosquito is most active from dusk to dawn, special operations forces, often active at night, are especially vulnerable. These limitations have long been recognized, and in 2010 the Army formalized a directive to develop a vaccine by issuing a Capability Development Document (CDD) for Vaccines for the Prevention of Malaria. The CDD states that such a vaccine must provide sterile immunity against infection in at least 80% of those receiving the vaccine that is sustained. The Peer Reviewed Medical Research Program (PRMRP) likewise has recognized the importance of malaria, listing malaria as a Topic Area and specifying as an Area of Encouragement to “develop methods to induce high levels of long-lived, broadly protective (against multiple strains) immunity.” The best approach to achieve these objectives is to induce immunity against the sporozoite forms of the parasite, which are the forms transmitted by the mosquito, and the subsequent liver forms, which develop over 5 to 6 days before erupting into the blood, which is where malaria does its damage. If the immune response induced by the vaccine eliminates the parasite at these early stages (stages that do not cause any harm to the person), it will prevent the dangerous blood stages that occur later in the infection and that are responsible for disease, death, and transmission back to the mosquito vector. Such a vaccine will protect the vaccinated person and safeguard others from ongoing transmission from the infected person. Sanaria, a biotechnology company, has responded by developing malaria vaccines based on sporozoites, the infectious form of the parasite transmitted to humans, as this is the only approach shown to induce high-level (>90%) protection. In a recent trial, Sanaria’s PfSPZ-CVac, which combines the sporozoite with a partner drug that kills the blood stages of the infection, 9/9 (100%) volunteers were protected when malaria was purposefully given to the volunteers after vaccination. In this randomized, controlled trial, the vaccine had no side effects. PfSPZ-CVac thus appears promising to meet the PRMRP objective for a safe vaccine. This proposal will support the conduct of a clinical trial of Sanaria’s PfSPZ-CVac in 480 Indonesian Soldiers. The trial will assess the safety and tolerability of PfSPZ-CVac and its ability to protect against both P. falciparum (Pf) and P. vivax (Pv) malaria during a
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710613
Entities
People
- Stephen L. Hoffman
Organizations
- Sanaria
- United States Army