This trial will evaluate whether relatively non-immune populations in endemic countries can effectively generate significant cellular and humoral immune responses that confer protection against P. falciparum infection after inoculation of aseptic, purified, vialed, metabolically active, non-replicating (live, radiation attenuated) Plasmodium falciparum sporozoites (PfSPZ Vaccine) administered intravenously (IV).

This is a single center, Phase 1, dose escalating, randomized, double blind, controlled trial. Seventy-three healthy male volunteers, aged 18 to 35 years will be recruited. The study will have 5 study groups that will include 49 volunteers who will be intravenously injected with PfSPZ Vaccine, 8 control volunteers who will receive normal saline and 16 additional control volunteers who will be recruited at the time of controlled human malaria infection (CHMI) at 3 and 24 weeks. The control volunteers will help better assess the occurrence of AEs compared to background disease patterns that occur in this tropical area, and the performance of the vaccine.

Inclusion Criteria:

• Healthy male aged between 18 - 35 years.
• Good health status based on history and clinical examination.
• Long term or permanent resident in or near Dar-es-Salaam.
• Able and willing to complete the study visit schedule over the one year follow up period, including the hospitalizations required for protocol compliance.
• Able and willing to complete the informed consent process conducted in English.
• Demonstrate understanding of the study and procedures by answering 20 questions from the Protocol & Study Procedures Understanding Checklist correctly with a maximum of two attempts.
• Agrees to inform study doctor of medical conditions and contraindications for participation in the study.
• Agrees to provide contact information to the study team for a household member who will serve as an emergency contact during trial participation.
• Willing to be attended by a study doctor and take medications, which may be prescribed by a study doctor, during study participation.
• Reachable (24/7) by mobile phone during the whole study period.
• Agrees not to participate in another study during the study period.
• Agrees not to donate blood during the study period.
• Willing to undergo HIV, hepatitis B and hepatitis C testing.
• Willing to undergo controlled human malaria infection (CHMI).

Exclusion Criteria:

• History of malaria in the past 5 years.
• Positive for malaria by thick blood smear at screening.
• Plans to travel outside the Dar-es-Salaam or Coast Region in first 12 months of the study.
• Previous receipt of an investigational malaria vaccine.
• Antibodies to parasites or selected parasite protein(s) above acceptable cut off established for the site
• History of arrhythmias or prolonged QT-interval or other cardiac disease or clinically significant abnormalities in electrocardiogram (ECG) at screening.
• History or indication of a history of drug or alcohol abuse interfering with normal social function.
• Use of chronic immunosuppressive drugs, antibiotics, or other immune modifying drugs within three months of study enrollment (inhaled and topical corticosteroids are allowed).
• Ongoing condition that could interfere with the interpretation of the study results or compromise the health of the volunteer.
• History of diabetes mellitus or cancer.
• Body Mass Index (BMI) below 18 or above 30 kg/m2.
• Any clinically significant deviation from the normal range in biochemistry or hematology blood tests or in urine analysis or electrolytes.
• Positive HIV, Hepatitis B virus or Hepatitis C virus tests.
• Participation in any other clinical study within 30 days prior to study enrollment.
• Known hypersensitivity, allergy, or other contra-indications to Coartem® or Malarone® including treatment taken by the volunteer that interferes with Coartem® or Malarone®.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including asplenia.
• Heterozygous or homozygous for sickle cell or homozygous for alpha thalassemia.
• Glucose-6-phosphate dehydrogenase deficiency
• Psychiatric condition that precludes compliance with the protocol; past or present psychoses; disorder requiring lithium; or within five years prior to enrollment, history of suicide plan or attempt.
• Any medical, psychiatric, social condition, or occupational reason that, in the judgment of the investigator, is a contraindication to protocol participation or impairs the volunteer's ability to give informed consent, increases the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
• History of 3 or more other immunizations within the six months before administration of the first dose of vaccine.
• Clinically active tuberculosis