Systems Analysis of the PfSPZ Vaccine in Kenyan Infants

The PfSPZ vaccine is a candidate vaccine targeting the Plasmodium falciparum parasite, which is the cause of the most lethal type of human malaria. This study used de-identified blood samples collected from 316 infants aged 5 to 12 months (inclusive) enrolled in a Phase 2, randomized, placebo-controlled trial (NCT02687373) of the PfSPZ malaria vaccine, conducted in a region of western Kenya where malaria transmission is high and perennial. The study began in July, 2016, after peak malaria transmission, and was completed in August, 2018. In this study, three doses of the PfSPZ Vaccine (4.5x105 PfSPZ, 9.0x105 PfSPZ, and 1.8x106 PfSPZ) were tested against a normal saline placebo comparator. In all four groups, doses were administered in 3 doses at 0, 8, and 16 weeks by direct venous inoculation. Vaccine efficacy was determined at 3, 6, and 12 months of follow-up after the third immunization. RNA was extracted from whole blood collected in PAXgene tubes before PfSPZ immunization, and two weeks after the third (final) dose, from 262 children for which sufficient material was available at both time points (82% of 316 enrolled children; 525 samples). RNA was depleted of globin and ribosome transcripts before library generation and sequencing on the Illumina NovaSeq platform. RNA-seq expression data was analyzed to determine blood transcriptional signatures, before and after PfSPZ vaccine immunization, that predicts sterile protection from naturally occurring P. falciparum infection or delayed parasitemia at 3 months post-immunization. Gene expression data will also be correlated to P. falciparum-specific IgG antibody and cellular responses to identify possible molecular correlates of vaccine-induced immunogenicity
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Inclusion Criteria:
• Healthy infants 5-12 months, inclusive
• HIV negative
• Able to participate for the duration of the study
• Parents/guardians over the age of 18 years, able and willing to provide informed consent/permission The consent/permission will be in writingFor adult parents or guardians who are illiterate, an impartial witness can sign the consent/permission form on behalf of the parent and the parent/guardian will provide a thumb print
Exclusion Criteria:
• Positive HIV test or breastfeeding infants, or children of a known HIV positive mother (per Kenyan guidelines, these HIV exposed breastfeeding children should be on co-trimoxazole)
• Refusal of HIV testing
• Elevated ALT (liver function test) ≥2x ULN ( ALT >84 U/L)
• Abnormal hematological parameters defined as: hemoglobin < 8 g/dl, WBC <1500/mm3, neutrophils <750/mm3, platelet count <75.000/mm3
• Abnormal renal function test with creatinine >0.9 mg/dL
• Known sickle cell disease and other inherited blood cell disorders like thalassemia and G6PD deficiency
• Current use of systemic immunosuppressant pharmacotherapy
• Current significant medical condition (cardiac, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory examination
• History of a splenectomy
• History of neurologic disorder (including seizures, other than uncomplicated febrile seizures)
• Known allergy to any component of the vaccine formulation, history of anaphylactic response to mosquito-bites, or known allergy to first or second line anti-malarials used to treat malaria
• Plan to participate in another investigational vaccine/drug research during or within 1 month of this study end
• Prior participation in a malaria vaccine trial
• Participation in the PfSPZ Vaccine Trial Part 1
• History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives
• Child/orphan in institutional care
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Study Start Date: July 21, 2016
Study Completion Date: August 14, 2018
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