Pfs230D1M-EPA/AS01 Vaccine, a Transmission Blocking Vaccine Against Plasmodium Falciparum, in an Age De-Escalation Trial of Children and a Family Compound Trial in Mali

* INCLUSION CRITERIA FOR GROUPS 1,2,3: All of the following criteria must be fulfilled for a volunteer to participate in this trial: 1. Meets age requirements for Arm currently being enrolled. 2. Available for the duration of the trial. 3. Family compound known resident or long-term resident (more than 1 year) of Doneguebougou, Mali or surrounding villages. 4. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 5. In good general health and without clinically significant medical history in the opinion of the investigator. 6. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to Study Day 0 and until 1 month after the last vaccination. * A reliable method of birth control includes one of the following: <!-- --> 1. Confirmed pharmacologic contraceptives (parenteral) delivery; 2. Intrauterine or implantable device EXCEPTIONS to required pregnancy prevention includes the following: 1. Postmenopausal state: defined as no menses for 12 months without an alternative medical cause 2. Surgical sterilization 3. Unmarried AND not sexually active AND menstruating OR not menstruating females 12-17 years of age 4. NOTE: if a female of childbearing potential s status changes during the course of vaccination through 1 month post vaccination (e.g. they become \>=18 years of age, married, or sexually active), the female will be required to start reliable contraception 7\. Willing to have blood samples stored for future research. INCLUSION CRITERIA FOR GROUP 4: All of the following criteria must be fulfilled for a volunteer to participate in this trial: 1. Meets age requirements for Arm currently being enrolled. 2. Available for the duration of the trial. 3. Family compound known resident or long-term resident (more than 1 year) of Doneguebougou, Mali or surrounding villages. 4. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. 5. In good general health and without clinically significant medical history in the opinion of the investigator. 6. Willing to have blood samples stored for future research. Inclusion Criteria for Groups 1, 2, 3, (Year 2) All of the following criteria must be fulfilled for a volunteer to continue to participate in this trial: 1\. Previously enrolled in the study and has received at least 1 vaccination. 2. Available for the duration of the trial. 3\. In good general health and without clinically significant medical history in the opinion of the investigator. 4\. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to scheduled vaccine dose #4 and until 1 month after the 4th vaccination. -A reliable method of birth control includes one of the following: 1. Confirmed pharmacologic contraceptives (parenteral) delivery; 2. Intrauterine or implantable device EXCEPTIONS to required pregnancy prevention includes the following: 1. Postmenopausal state: defined as no menses for 12 months without an alternative medical cause 2. Surgical sterilization 3. Unmarried AND not sexually active AND menstruatingOR not menstruating females 12-17 years of age 4. NOTE: if a female of childbearing potential s status changes during the course of vaccination through 1 month post vaccination (e.g. they become greater than or equal to 18 years of age, married, or sexually active), the female will be required to start reliable contraception 5. Willing to have blood samples stored for future research. Inclusion Criteria for Group 4 (Year 2): All of the following criteria must be fulfilled for a volunteer to continue to participate in this trial: 1. Previously enrolled in the study 2. Available for the duration of the trial. 3. In good general health and without clinically significant medical history in the opinion of the investigator. 4. Willing to have blood samples stored for future research. EXCLUSION CRITERIA FOR GROUPS 1, 2, 3: An individual will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (beta-hCG) test (if female). NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing 2. Menstruating females 11 years of age and younger. (In order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group.) 3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject s age. 4. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels outside the local laboratory defined limits of normal. (Subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and \<= Grade 2.) 5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory defined upper limit of normal. (Subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and \<= Grade 2.) 6. Infected with HIV 7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. 8. Clinically significant prolonged QTc (\>450 milliseconds) on screening EKG 9. History of receiving any investigational product within the past 30 days. 10. Current or planned participation in an investigational vaccine study until the last required protocol visit. 11. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. 12. History of a severe allergic reaction or anaphylaxis. 13. Known: * Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years. * Autoimmune or antibody-mediated disease including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia. * Immunodeficiency syndrome. * Seizure disorder (exception: history of simple febrile seizures) * Asplenia or functional asplenia. * Use of chronic (\>=14 days) oral or intravenous (IV) corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone \>10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0. * Allergy to latex or neomycin * Adverse reaction to hepatitis A and/or typhoid and/or meningococcal vaccine in the past * Adverse reaction to artemether/lumefantrine in the past 14. Receipt of: -Live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks to enrollment. * Immunoglobulins and/or blood products within the past 6 months. * Investigational malaria vaccine in the last 2 years. 15. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol. Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the PI. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the investigator. Exclusion Criteria for Group 4: An individual will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject s age. 2. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. 3. Clinically significant prolonged QTc (by sex/age) on screening EKG 4. History of adverse reactions to artemether/lumefantrine in the past 5. History of receiving any investigational product within the past 30 days. 6. Current or planned participation in an investigational vaccine study until the last required protocol visit. 7. Receipt of: -Investigational malaria vaccine in the last 2 years. 8. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol. Exclusion Criteria for Groups 1, 2, 3 (Year 2): An individual will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (beta-hCG) test (if female). NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing 2. Menstruating females 11 years of age and younger. (In order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group.) 3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject s age. 4. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels outside the local laboratory defined limits of normal. (Subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and less than or equal to Grade 2.) 5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory defined upper limit of normal. (Subjects may be included at the investigator s discretion for not clinically significant values outside of normal range and less than or equal to Grade 2.) 6. Infected with HIV 7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. 8. History of receiving any investigational product within the past 30 days. 9. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. 10. History of a severe allergic reaction or anaphylaxis. 11. Known: -Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years. -Autoimmune or antibody-mediated disease including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren s syndrome, or autoimmune thrombocytopenia. * Immunodeficiency syndrome. * Seizure disorder (exception: history of simple febrile seizures) * Asplenia or functional asplenia. * Use of chronic (greater than or equal to 14 days) oral or intravenous (IV) corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone \>10 mg/day) or immunosuppressive drugs within 30 days of Study Day 0. * Allergy to latex or neomycin * Adverse reaction to hepatitis A and/or typhoid and/or meningococcal vaccine in the past * Adverse reaction to artemether/lumefantrine in the past 12. Receipt of: * Live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks to enrollment. * Immunoglobulins and/or blood products within the past 6 months. 13. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol. Exclusion Criteria for Group 4 (Year 2): An individual will be excluded from participating in this trial if any one of the following criteria is fulfilled: 1\. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol at a level appropriate for the subject s age. 2\. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. 3\. History of adverse reactions to artemether/lumefantrine in the past 4\. History of receiving any investigational product within the past 30 days. 5\. Current or planned participation in an investigational vaccine study until the last required protocol visit. 6\. Receipt of: * Investigational malaria vaccine in the last 2 years. 7\. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or would render the subject unable to comply with the protocol.