A novel malaria vaccine candidate is well tolerated and induced functionally active antibodies when formulated with Alhydrogel® or glucopyranosyl lipid adjuvant-based adjuvants, according to a study published in Clinical Infectious Diseases.

Pregnancy-associated malaria has been estimated to result in 20,000 maternal and 200,000 infant deaths. The current prevention strategy for pregnancy-associated malaria includes intermittent preventative treatment and impregnated bed nets. To complement this current prevention strategy and other existing interventions, the authors of this study developed a malaria vaccine candidate that targeted the major virulence mechanism in pregnancy-associated malaria by reducing sequestration of asexual “blood-stage” parasites in the placenta. The vaccine candidate is based on a recombinant fragment of VAR2CSA, which is a protein responsible for binding to the placenta (ClinicalTrials.gov identifier: NCT02647489).

Between 2016 and 2017, researchers recruited 36 volunteers. The study participants were immunized with 3 intramuscular injections; 9 people received 20 µg and 27 received 50 µg of PAMVAC adjuvanted with either Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion or in a liposomal formulation with QS21. All vaccinations were given within a prespecified time window of 28 to 35 days and volunteers were observed for 6 months following the last immunization. The primary end point was the number and grade of adverse events and serious adverse events that were categorized as possibly, likely, or definitely related to vaccination. Adverse event severity was graded as mild (grade 1), moderate (grade 2), severe (grade 3), or potentially life-threatening (grade 4).

PAMVAC was generally well tolerated at both dose levels (20 µg and 50 µg). No serious adverse events occurred throughout the duration of the study. However, there were 262 adverse events. Of these,188 events were grade 1, 62 were grade 2, 10 were grade 3, and 2 were grade 4. A total of 94 adverse events (10 that were grade 2 and 2 were grade 3) were determined to be at least possibly related to the vaccine. There were similar adverse event patterns among the 3 adjuvants, and adverse events did not increase in either frequency or severity at booster doses.

Further, PAMVAC induced seroconversion in all the volunteers regardless of dose level and adjuvant. PAMVAC-specific antibody levels were the highest with PAMVAC and glucopyranosyl lipid adjuvant in stable emulsion; participants in this group also had the highest binding-inhibitory capacity. Of note, compared with the Alhydrogel group, PAMVAC-Ig G plasma level 4 weeks after the last vaccination was 6.2-fold higher in the glucopyranosyl lipid adjuvant group (95%CI, 3.6-10.7). The liposomal group showed a 4.4-fold higher IgG plasma level compared with the Alhydrogel group (95% CI, 2.6-7.6). This difference was more pronounced at the end of follow-up (day 252), with 8.5-fold (95% CI, 4.3-16.6) and 5.5-fold (95% CI, 2.8-10.8) increases in the glucopyranosyl lipid adjuvant group and the liposomal group compared with the Alhydrogel group, respectively.

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Overall, the study authors concluded that, “PAMVAC is well tolerated in healthy, malaria-naive adults, formulated with Alhydrogel [or glucopyranosyl lipid adjuvant in stable emulsion or a liposomal formulation with QS21].”

Reference

Mordmüller B, Sulyok M, Egger-Adam D, et al. First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, vaccine candidate to prevent pregnancy-associated malaria [published online January 10, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciy1140/5281109