Promising Early Results With P27A Candidate Vaccine for Malaria Prevention

vaccine, syringe
vaccine, syringe
Early findings show that the P27A candidate vaccine for malaria prevention appeared to be safe and induced a strong immunogenic response with parasite growth inhibitory capacity.

Early findings show that the P27A vaccine candidate for malaria prevention appears to be safe and induced a strong immunogenic response with the capacity to inhibit parasite growth, especially when formulated with GLA-SE, according to a new report published in Clinical Infectious Diseases.

P27A is an unstructured peptide segment from the TEX1 protein of Plasmodium falciparum, which has been shown to be a target for human antibodies inhibiting parasite growth. The study evaluated the safety and immunogenicity of a P27A peptide vaccine in both European adults who had not been exposed to malaria and African adults who had.

In this phase 1a/1b trial, the P27A antigen, adjuvanted with Alhydrogel®, Glucopyranosil Lipid Adjuvant-Stable Emulsion (GLA-SE) or a rabies control vaccine (Verorab), was given to 16 malaria non-exposed and 40 malaria exposed participants on days 0, 28 and 56. The phase 1a participants were separated into 2 groups of 8 individuals each and injected intramuscularly with 50μg of P27A antigen adjuvanted with Alhydrogel (group CH-Alum/50) or 2.5μg GLA-SE (group CH-GLA2.5/50). The phase 1b volunteers were separated and randomly assigned in a dose escalating manner to 4 cohorts of 10 participants each: 8 were injected intramuscularly with 50μg P27A and Alhydrogel (group TZ-Alum/50), 8 with 10μg P27A and 2.5μg GLA-SE (group TZ-GLA2.5/10), 8 with 50μg P27A and 2.5μg GLA-SE (group TZ-GLA2.5/50), and 8 with 50μg P27A and 5μg GLA-SE (group TZ-GLA5/50). In each cohort, 2 subjects were injected with rabies vaccine Verorab® as control (group TZ-Ver).

A specific anti-P27A IgG antibody response in the non-exposed cohort peaked on day 84 with median titers of 3200 (200; 12800) and 51200 (3200; 204800) in groups adjuvanted with CH-Alum/50 and CH-GLA2.5/50, respectively. The 10-fold difference in the titers at day 84 persisted between the two groups at day 238 (week 34), with a median titer of 9600. In exposed individuals, IgG titers at day 84 in groups TZ-Alum/50, TZ-GLA2.5/10 and TZ-GLA2.5/50 reached median titers of 4800 (100; 9051), 2400 (800; 12800), and 6400 (1600; 12800), respectively, and were in the same range as individuals adjuvanted with CH-Alum/50. Responses in the TZ-GLA2.5/50 group persisted significantly longer vs TZ-Alum/50 (Kruskal-Wallis; P =0.0008, with post-test P = 0.0103 at day 238). Overall, adverse events and antibody responses were significantly lower in the individuals exposed to malaria than the individuals in the non-exposed group.

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“The value of antigen P27A should now be challenged in preliminary efficacy trials using a controlled human malaria infection (CHMI) in non-exposed and exposed subjects,” wrote the investigators.

Reference

Steiner-Monard V, Kamaka K, et al. The candidate blood stage malaria vaccine P27Ainduces a robust humoral response in a fast track to the field phase Itrial in exposed and nonexposed volunteers [published online June 26, 2018]. Clin Infect Dis. doi:10.1093/cid/ciy514