Cross-reactive inhibitory antibody and memory B cell responses to variant strains of Duffy binding protein II at post-Plasmodium vivax infection

• Published in: PloS one Vol. 17; no. 10; p. e0276335
• Main Authors: Thawornpan, Pongsakorn, Changrob, Siriruk, Kochayoo, Piyawan, Wangriatisak, Kittikorn, Ntumngia, Francis B., De, Sai Lata, Han, Eun-Taek, Adams, John H., Chootong, Patchanee
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.10.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Animals; Antibodies; Antibodies, Blocking; Antibodies, Protozoan; Antigens; Antigens, Protozoan; B cells; Biology and Life Sciences; Carrier Proteins; Drug resistance; E coli; Erythrocytes; Haplotypes; Health aspects; Humoral immunity; Immunity; Immunization; Immunological memory; Infections; Ligands; Lymphocytes T; Malaria; Malaria Vaccines; Malaria, Vivax; Medicine and Health Sciences; Memory B Cells; Mice; Mice, Inbred BALB C; Patients; Plasmids; Plasmodium vivax; Polymerase chain reaction; Prevention; Protein binding; Proteins; Protozoan Proteins; Receptors, Cell Surface; Research and Analysis Methods; Vaccines; Vector-borne diseases; Viral antibodies; Thailand; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0276335

Duffy binding protein region II (DBPII) is considered a strong potential vaccine candidate of blood-stage P . vivax . However, the highly polymorphic nature of this protein often misdirects immune responses, leading them to be strain-specific. Details of cross-reactive humoral immunity to DBPII variants have therefore become an important focus for the development of broadly protective vaccines. Here, cross-reactive humoral immunity against a panel of Thai DBPII variants (DBL-THs) was demonstrated in immunized BALB/c mice and P . vivax patients, by in vitro erythrocyte-binding inhibition assay. Sera from immunized animals showed both strain-transcending (anti-DBL-TH2 and -TH4) and strain-specific (anti-DBL-TH5, -TH6 and -TH9) binding to DBL-TH variants. Using anti-DBL-TH sera at 50% inhibitory concentration (IC50) of the homologous strain, anti-DBL-TH2 sera showed cross inhibition to heterologous DBL-TH strains, whereas anti-DBL-TH5 sera exhibited only strain-specific inhibition. In P . vivax patients, 6 of 15 subjects produced and maintained cross-reactive anti-DBL-TH inhibitory antibodies through the 1-year post-infection timepoint. Cross-reactive memory B cell (MBC) responses to DBL-TH variants were analyzed in subjects recovered from P . vivax infection (RC). The plasma samples from 5 RC subjects showed broad inhibition. However, MBC-derived antibodies of these patients did not reveal cross-inhibition. Altogether, broadly anti-DBP variant inhibitory antibodies developed and persisted in P . vivax infections. However, the presence of cross-reactive anti-DBL-TH inhibitory function post-infection was not related with MBC responses to these variants. More detailed investigation of long-lasting, broadly protective antibodies to DBPII will guide the design of vivax malaria vaccines.