npj Vaccines (Dec 2021)

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques

  • Puthupparampil V. Scaria,
  • Charles Anderson,
  • Olga Muratova,
  • Nada Alani,
  • Hung V. Trinh,
  • Steven T. Nadakal,
  • Irfan Zaidi,
  • Lynn Lambert,
  • Zoltan Beck,
  • Emma K. Barnafo,
  • Kelly M. Rausch,
  • Chris Rowe,
  • Beth Chen,
  • Gary R. Matyas,
  • Mangala Rao,
  • Carl R. Alving,
  • David L. Narum,
  • Patrick E. Duffy

DOI
https://doi.org/10.1038/s41541-021-00407-3
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 10

Abstract

Read online

Abstract Malaria transmission-blocking vaccines candidates based on Pfs25 and Pfs230 have advanced to clinical studies. Exoprotein A (EPA) conjugate of Pfs25 in Alhydrogel® developed functional immunity in humans, with limited durability. Pfs230 conjugated to EPA (Pfs230D1-EPA) with liposomal adjuvant AS01 is currently in clinical trials in Mali. Studies with these conjugates revealed that non-human primates are better than mice to recapitulate the human immunogenicity and functional activity. Here, we evaluated the effect of ALFQ, a liposomal adjuvant consisting of TLR4 agonist and QS21, on the immunogenicity of Pfs25-EPA and Pfs230D1-EPA in Rhesus macaques. Both conjugates generated strong antibody responses and functional activity after two vaccinations though activity declined rapidly. A third vaccination of Pfs230D1-EPA induced functional activity lasting at least 9 months. Antibody avidity increased with each vaccination and correlated strongly with functional activity. IgG subclass analysis showed induction of Th1 and Th2 subclass antibody levels that correlated with activity.