Promising Early Results With P27A Candidate Vaccine for Malaria Prevention

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Investigators propose unstructured segment from the TEX1 of P. falciparum as an ideal candidate for a synthetic peptide vaccine.
Investigators propose unstructured segment from the TEX1 of P. falciparum as an ideal candidate for a synthetic peptide vaccine.

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.

“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

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