Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

Abstract

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

• Authors: Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J Campo, Meral Esen, Adam J Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R James, Peter F Billingsley, K C Natasha, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G Eappen, Tao Li, Richard E Stafford, Minglin Li, Phil L Felgner, Robert A Seder, Thomas L Richie, B Kim Lee Sim, Stephen L Hoffman, Peter G Kremsner
• Journal: Nature (Nature) Vol. 542 Issue 7642 Pg. 445-449 (02 23 2017) ISSN: 1476-4687 [Electronic] England
• PMID: 28199305 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Protozoan
• Malaria Vaccines
• Vaccines, Attenuated
• Chloroquine

Topics

• Adolescent
• Adult
• Antibodies, Protozoan (blood, immunology)
• Chloroquine (therapeutic use)
• Double-Blind Method
• Healthy Volunteers
• Humans
• Immunologic Memory (immunology)
• Malaria Vaccines (administration & dosage, immunology)
• Malaria, Falciparum (blood, immunology, parasitology, prevention & control)
• Middle Aged
• Plasmodium falciparum (classification, immunology)
• Sporozoites (immunology)
• T-Lymphocytes (immunology)
• Time Factors
• Vaccines, Attenuated (administration & dosage, immunology)
• Young Adult