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B cell clonal expansion and mutation in the immunoglobulin heavy chain variable domain in response to Pfs230 and Pfs25 malaria vaccines


Coelho, Camila H; Galson, Jacob D; Trück, Johannes; Duffy, Patrick E (2022). B cell clonal expansion and mutation in the immunoglobulin heavy chain variable domain in response to Pfs230 and Pfs25 malaria vaccines. International Journal for Parasitology, 52(11):707-710.

Abstract

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. Here, we describe clonal expansion in the variable region of immunoglobulin heavy chains (VH) of antigen-specific single B cells collected from humans immunised 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 the enhanced activity of Pfs230 antibodies by complement, might justify the outstanding activity of Pfs230D1 as a TBV candidate.

Abstract

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. Here, we describe clonal expansion in the variable region of immunoglobulin heavy chains (VH) of antigen-specific single B cells collected from humans immunised 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 the enhanced activity of Pfs230 antibodies by complement, might justify the outstanding activity of Pfs230D1 as a TBV candidate.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Parasitology
Health Sciences > Infectious Diseases
Language:English
Date:October 2022
Deposited On:03 Jan 2023 08:13
Last Modified:28 Jun 2024 01:37
Publisher:Elsevier
ISSN:0020-7519
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.ijpara.2021.11.008
PubMed ID:34896314