Safety and immunogenicityof Pfs25-EPA/ alhydrogel1, a transmission blocking vaccine against Plasmodium falciparum: An open label study in malaria naïve adults

Kawsar Rasmy Talaat, Ruth D. Ellis, Janet Hurd, Autumn Hentrich, Erin Gabriel, Noreen A Hynes, Kelly M. Rausch, Daming Zhu, Olga Muratova, Raul Herrera, Charles Anderson, David Jones, Joan Aebig, Sarah Brockley, Nicholas J. MacDonald, Xiaowei Wang, Michael P. Fay, Sara A. Healy, Anna P Durbin, David L. NarumYimin Wu, Patrick E. Duffy

Research output: Contribution to journalArticle

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, doseescalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel1. 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/Alhydrogel1 in a malaria-endemic population.

Original languageEnglish (US)
Article numbere0163144
JournalPLoS One
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Talaat, K. R., Ellis, R. D., Hurd, J., Hentrich, A., Gabriel, E., Hynes, N. A., Rausch, K. M., Zhu, D., Muratova, O., Herrera, R., Anderson, C., Jones, D., Aebig, J., Brockley, S., MacDonald, N. J., Wang, X., Fay, M. P., Healy, S. A., Durbin, A. P., ... Duffy, P. E. (2016). Safety and immunogenicityof Pfs25-EPA/ alhydrogel1, a transmission blocking vaccine against Plasmodium falciparum: An open label study in malaria naïve adults. PLoS One, 11(10), [e0163144]. https://doi.org/10.1371/journal.pone.0163144