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

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

doi:10.1371/journal.pntd.0005070

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

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

21 Citations (Scopus)

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Abstract

BACKGROUND: 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.

METHODOLOGY/PRINCIPAL FINDINGS: 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.

CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.

TRIAL REGISTRATION: Identifier: NCT01082341.

Original language	English
Article number	e0005070
Journal	P L o S Neglected Tropical Diseases (Online)
Volume	10
Issue number	10
ISSN	1935-2735
DOIs	https://doi.org/10.1371/journal.pntd.0005070
Publication status	Published - 19 Oct 2016
Externally published	Yes

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19. 2016 PNTD Arevalo & Lopez-Perez Protective Efficacy of PvRAS in Colombian Volunteers- A Randomized Controlled Trial
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Arévalo-Herrera, M., Vásquez-Jiménez, J. M., Lopez-Perez, M., Vallejo, A. F., Amado-Garavito, A. B., Céspedes, N., Castellanos, A., Molina, K., Trejos, J., Oñate, J., Epstein, J. E., Richie, T. L., & Herrera, S. (2016). Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. P L o S Neglected Tropical Diseases (Online), 10(10), Article e0005070. https://doi.org/10.1371/journal.pntd.0005070

Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial. / Arévalo-Herrera, Myriam; Vásquez-Jiménez, Juan M; Lopez-Perez, Mary et al.
In: P L o S Neglected Tropical Diseases (Online), Vol. 10, No. 10, e0005070, 19.10.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Arévalo-Herrera, M, Vásquez-Jiménez, JM, Lopez-Perez, M, Vallejo, AF, Amado-Garavito, AB, Céspedes, N, Castellanos, A, Molina, K, Trejos, J, Oñate, J, Epstein, JE, Richie, TL & Herrera, S 2016, 'Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers: A Randomized Controlled Trial', P L o S Neglected Tropical Diseases (Online), vol. 10, no. 10, e0005070. https://doi.org/10.1371/journal.pntd.0005070

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abstract = "BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.TRIAL REGISTRATION: Identifier: NCT01082341.",

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T1 - Protective Efficacy of Plasmodium vivax Radiation-Attenuated Sporozoites in Colombian Volunteers

T2 - A Randomized Controlled Trial

AU - Arévalo-Herrera, Myriam

AU - Vásquez-Jiménez, Juan M

AU - Lopez-Perez, Mary

AU - Vallejo, Andrés F

AU - Amado-Garavito, Andrés B

AU - Céspedes, Nora

AU - Castellanos, Angélica

AU - Molina, Karen

AU - Trejos, Johanna

AU - Oñate, José

AU - Epstein, Judith E

AU - Richie, Thomas L

AU - Herrera, Sócrates

PY - 2016/10/19

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N2 - BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.TRIAL REGISTRATION: Identifier: NCT01082341.

AB - BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria.TRIAL REGISTRATION: Identifier: NCT01082341.

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DO - 10.1371/journal.pntd.0005070

M3 - Journal article

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SN - 1935-2735

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JO - P L o S Neglected Tropical Diseases (Online)

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

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