Assays to Support Development of Malaria Transmission Blocking Vaccines

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

We published the following findings in FY2022: 1. Coelho CH, Galson JD, Trck J, Duffy PE. B cell clonal expansion and mutation in the immunoglobulin heavy chain variable domain in response to Pfs230 and Pfs25 malaria vaccines. 2021. International Journal of Parasitology. Dec 9. Malaria transmission-blocking vaccines induce antibodies that target Plasmodium in the mosquito vector. We recently reported that Pfs230 vaccine achieves activity superior to Pfs25 in humans. In this study, we described clonal expansion in the variable region of immunoglobulin heavy chains (VH) of antigen-specific single B cells, collected from humans immunized with Pfs230D1-EPA or Pfs25-EPA conjugate vaccines formulated in Alhydrogel. Based on studies of CD27+ memory B cells following Pfs230 vaccination, clonal expansion and somatic hypermutation was seen in four of five subjects. Pfs25 did not induce sufficient CD27+ cells for sorting; based instead on CD19+ Pfs25-reactive B cells, clonal expansion was only seen in two of five subjects. Clonal expansions and mutations in Pfs230-specific single B cells, combined with enhanced activity of Pfs230 antibodies by complement, might justify the outstanding activity of Pfs230D1 as a TBV candidate.