Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults

PLoS One. 2016 Oct 17;11(10):e0163144. doi: 10.1371/journal.pone.0163144. eCollection 2016.

Abstract

Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Protozoan / blood
  • Antibody Affinity / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Malaria Vaccines / adverse effects
  • Malaria Vaccines / chemistry
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / prevention & control*
  • Malaria, Falciparum / transmission
  • Microscopy, Fluorescence
  • Middle Aged
  • Pain / etiology
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / adverse effects
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Protozoan Proteins / metabolism
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology*
  • Vaccines, Conjugate / immunology
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Malaria Vaccines
  • Protozoan Proteins
  • Recombinant Proteins
  • Vaccines, Conjugate
  • transmission-Blocking Vaccine based on Pfs25

Grant support

This research was funded in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH (Contract HHSN266200400077C) and by PATH Malaria Vaccine Initiative (Contract GAT.0888-11-05311-CTA). Employees of NIAID were integral in the study design, data collection and analysis and manuscript preparation.