Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial

• Published in: PLoS neglected tropical diseases Vol. 10; no. 10; p. e0005070
• Main Authors: Arévalo-Herrera, Myriam, Vásquez-Jiménez, Juan M., Lopez-Perez, Mary, Vallejo, Andrés F., Amado-Garavito, Andrés B., Céspedes, Nora, Castellanos, Angélica, Molina, Karen, Trejos, Johanna, Oñate, José, Epstein, Judith E., Richie, Thomas L., Herrera, Sócrates
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.10.2016; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Animals; Anopheles - parasitology; Antibodies, Protozoan - blood; Aquatic insects; Biology and Life Sciences; Causes of; Clinical trials; Colombia; Duffy Blood-Group System; Female; Genetic aspects; Health aspects; Humans; Immunization; Immunization - adverse effects; Immunization - methods; Immunoglobulin G - blood; Insect bites; Insect Bites and Stings; Malaria; Malaria vaccines; Malaria Vaccines - administration & dosage; Malaria Vaccines - immunology; Malaria, Vivax - ethnology; Malaria, Vivax - immunology; Malaria, Vivax - parasitology; Malaria, Vivax - prevention & control; Male; Medicine and Health Sciences; Middle Aged; Mosquitoes; Pharmaceutical industry; Physiological aspects; Plasmodium vivax; Plasmodium vivax - immunology; Plasmodium vivax - physiology; Plasmodium vivax - radiation effects; Prevention; Research and Analysis Methods; Single-Blind Method; Sporozoites - radiation effects; Tropical diseases; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Vector-borne diseases; Volunteers; Young Adult; Colombia; United States > US; Maryland
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005070

Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. A randomized, single-blinded trial was conducted. Duffy positive (Fy+; Pv susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) Pv-infected Anopheles mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (Pv refractory) volunteers was immunized with bites from non-irradiated Pv-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated Pv-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8-13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-PvCS response was associated with protection. Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria. Identifier: NCT01082341.