Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial.
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 wa...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-10-01
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| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC5070852?pdf=render |
| _version_ | 1828158477976993792 |
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| author | Myriam Arévalo-Herrera Juan M Vásquez-Jiménez Mary Lopez-Perez Andrés F Vallejo Andrés B Amado-Garavito Nora Céspedes Angélica Castellanos Karen Molina Johanna Trejos José Oñate Judith E Epstein Thomas L Richie Sócrates Herrera |
| author_facet | Myriam Arévalo-Herrera Juan M Vásquez-Jiménez Mary Lopez-Perez Andrés F Vallejo Andrés B Amado-Garavito Nora Céspedes Angélica Castellanos Karen Molina Johanna Trejos José Oñate Judith E Epstein Thomas L Richie Sócrates Herrera |
| author_sort | Myriam Arévalo-Herrera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T23:45:59Z |
| format | Article |
| id | doaj.art-d7bfd7de5fff4305944a4becfb78b0b5 |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-04-11T23:45:59Z |
| publishDate | 2016-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-d7bfd7de5fff4305944a4becfb78b0b52022-12-22T03:56:39ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-10-011010e000507010.1371/journal.pntd.0005070Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial.Myriam Arévalo-HerreraJuan M Vásquez-JiménezMary Lopez-PerezAndrés F VallejoAndrés B Amado-GaravitoNora CéspedesAngélica CastellanosKaren MolinaJohanna TrejosJosé OñateJudith E EpsteinThomas L RichieSócrates HerreraImmunizing 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.http://europepmc.org/articles/PMC5070852?pdf=render |
| spellingShingle | Myriam Arévalo-Herrera Juan M Vásquez-Jiménez Mary Lopez-Perez Andrés F Vallejo Andrés B Amado-Garavito Nora Céspedes Angélica Castellanos Karen Molina Johanna Trejos José Oñate Judith E Epstein Thomas L Richie Sócrates Herrera Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. PLoS Neglected Tropical Diseases |
| title | Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. |
| title_full | Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. |
| title_fullStr | Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. |
| title_full_unstemmed | Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. |
| title_short | Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. |
| title_sort | protective efficacy of plasmodium vivax radiation attenuated sporozoites in colombian volunteers a randomized controlled trial |
| url | http://europepmc.org/articles/PMC5070852?pdf=render |
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