Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein
Journal Article
·
· Journal of Molecular Biology
- The Scripps Research Inst., La Jolla, CA (United States)
- Johns Hopkins Univ., Baltimore, MD (United States). Malaria Research Inst.
- Atreca Inc., Redwood City, CA (United States)
- PATH Center for Vaccine Innovation and Access, Washington, DC (United States)
- The Scripps Research Inst., La Jolla, CA (United States); The Scripps Research Inst., La Jolla, CA (United States). Skaggs Inst. for Chemical Biology
Malaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA4 peptide shows that the central NPNA forms a type I β-turn and is the main recognition motif. In most anti-NANP antibodies studied to date, a germline-encoded Trp is used to engage the Pro in NPNA β-turns, but here the Trp interacts with the first Asn. This “conserved” Trp, however, can arise from different germline genes and be located in the heavy or the light chain. Variation in the terminal ψ angles of the NPNA β-turns results in different dispositions of the subsequent NPNA and, hence, different stoichiometries and modes of antibody binding to rsCSP. Diverse protective antibodies against NANP repeats are therefore not limited to a single germline gene response or mode of binding.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- Bill and Melinda Gates Foundation; USDOE Office of Science (SC)
- Grant/Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1839762
- Alternate ID(s):
- OSTI ID: 1834868
- Journal Information:
- Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Journal Issue: 4 Vol. 432; ISSN 0022-2836
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Comparison of ELISA with electro-chemiluminescence technology for the qualitative and quantitative assessment of serological responses to vaccination
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journal | April 2020 |
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