This is a randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) vaccinated with three doses of a synthetic derivative of the CS protein of Plasmodium vivax to determine their protective efficacy.

Then volunteers will be subject to an infectious challenge (Controlled Human Malaria Infection) to assess the infectivity of gametocytes in the blood early stage of P. vivax in Anopheles albimanus mosquitoes.

This study is a prospective controlled, blinded clinical trial, designed to establish the protective efficacy induced by the vaccine PvCSP between human volunteers with and without history of malaria. Volunteers will be recruited in Cali, Colombia and Quibdó, Colombia.

Study subjects: This study will require the involvement of two types of volunteers, parasite donors and volunteers for immunization

Parasite donors: 5-15 P. vivax-infected patients who will serve as parasites donors for experimental infection of mosquitoes, who will be enrolled in the endemic area.

Volunteers for immunization: Two other groups of volunteers will be immunized with the PvCSP vaccine. A group of 60 people without previous exposure to malaria (naïve) and another 60 people with a history of previous malaria infection (pre-immune).

Methodology Recruitment of infected patients: Parasite donors will be recruited among P. vivax infected patients attending a diagnostic center in the endemic area.

Infection of mosquito's blood from donors will be used to feed three-day-old mosquitoes by artificial membrane feeding technique. At day 7, a sample of mosquitoes will be examined to determine the level of infection by dissection of the mosquito's gut. On day 14, a small number of mosquitoes with a good degree of infectivity will be used to infect challenged volunteers.

Recruitment of pre-immune and naive volunteers: Volunteers for the immunization stage will be recruited both in the city of Cali (Colombia), non-endemic region, and in Quibdó (Colombia), a malaria endemic region, through various activities such as conferences, meetings and other strategies previously approved by the IRB, like posters, radio advertising flyers and social media.

Immunization: Volunteers will be immunized with the vaccine (n=60) or placebo (n=60).

Follow-up of volunteers will be performed under medical vigilance during the first hour following the immunization to detect any adverse reaction. After the first hour period a medical exam will be made. Eight hours after immunization, each volunteer will be contacted via telephone to assess physical condition. Any adverse event (AE) will be registered.

Subsequent follow up will be made on the day next to immunization and 1 or 2 weeks before the next immunization by a new clinical evaluation and AE report. Volunteers will be instructed to contact the research staff at any moment.

Infection of volunteers immunized volunteers will be challenged on day ~150 of the study, 1 month after the third immunization by the bite of 2-4 infected mosquito. A "feeding cage" will be placed on the forearm of a volunteer for 10 minutes, allowing that the feeding window, which will be covered by a mesh surface be placed against the volunteer's skin.

Volunteers will be instructed about the signs and symptoms of malaria and they will have a daily telephone contact during the first 6 days.

Between days 7 and 23 the volunteers will be asked to go to the Clinical Trials Unit daily to establish the presence or absence of disease through thick blood smear and samples will be collected for retrospective real time PCR P. vivax.

From day 23 until day 31, volunteers will receive physical and laboratory evaluation every other day and will have daily telephone contact.

Once the patients present signs and symptoms of the disease curative treatment will be immediately provided, and 15 ml of blood will be drawn, which will be used for immune response assessment.

If the volunteers do not develop the disease during the follow-up period, on day 31 they will be given antimalarial treatment.

Treatment Volunteers will be treated with antimalarial drugs approved by the Colombian Ministry of Social Health: chloroquine (three (3) doses: 600 mg initially, followed by 450 mg at 24, and 48 hours), associated with primaquine (30mg/day) for 14 days. All the volunteers will be asked to return two weeks after starting treatment for a thick blood smear test to ensure cure of malaria.

Inclusion Criteria:

Naïve group:

1. Non-pregnant, healthy men and women between 18-45 years old.
2. Freely and voluntarily sign an IC, accompanied by two witnesses who must also sign.
3. Absence history of malaria infection.
4. To have negative serology for the PvCS protein by the ELISA test.
5. For women, not be pregnant.
6. Use of an adequate contraceptive method from the beginning until the contraceptive restriction is lifted by a study doctor, at the end of the study.
7. To accept not to travel to areas considered as endemic for malaria from the infectious challenge period and to the end of its follow-up (1 month).
8. Be reachable by phone throughout the study period.
9. To be Duffy positive (Fy +).
10. Have Hemoglobin (Hb) levels> 11 g / dl.
11. Be willing to participate during the period in which the study will take place.
12. Not be participating in another clinical study.
13. Be affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)

Semi-immune group:

1. Non-pregnant, healthy men and women between 18-45 years old,
2. Freely and voluntarily sign an informed consent, accompanied by two witnesses who will also sign.
3. Have a history of malaria infection (s) and positive serological tests (ELISA) for P. vivax.
4. For women, not be pregnant or nursing.
5. For women, use of adequate contraception from inception until the contraceptive restriction is lifted by a study physician.
6. Be a permanent resident of the municipality of Quibdó during the study.
7. Be reachable by phone throughout the study period.
8. Availability to participate during the period in which the study will take place.
9. Be affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)

Exclusion Criteria:

Naïve group:

1. Glucose 6 phosphate dehydrogenase deficiency (G-6-P-D).
2. Present any hemoglobinopathy (eg HbS).
3. Personal history of allergies to medications or insect bites.
4. Have received vaccination against malaria.
5. Clinical or laboratory abnormalities determined by the investigator (s).
6. IFAT> 1:20 for P. vivax in screening tests.
7. Have lived in a malaria-endemic region during the 12 months before the study.
8. Clinical or laboratory evidence of systemic disease, including kidney, liver, cardiovascular, pulmonary, psychiatric, or other diseases that may negatively impact and alter study results.
9. Evidence of active hepatitis B or Hepatitis C infection
10. Evidence of active HIV infection.
11. History of transfusion of any blood product in the 6 (six) months before the study.
12. Plan to have surgery from the recruitment period to the end of the post-challenge follow-ups.
13. Presence or history of autoimmune disease (lupus, rheumatoid arthritis, thyroiditis, or other).
14. Splenectomized volunteers.
15. Volunteers in treatment with drugs with activity on the immune system (steroids, immunosuppressive agents, or immunomodulators).
16. History of alcoholism or drug abuse defined as a habit that interferes with the normal social functioning of the individual.
17. Any condition that may interfere with the ability to provide a free and voluntary IC.
18. Not being affiliated with the general health social security system of Colombia, in any of its regimes (subsidized or contributory)

Semi-immune group:

1. IFAT negative (<1:20) for P. vivax in screening tests.
2. The other criteria used in the case of naïve volunteers, except the antecedent of having lived in the endemic area.