Abstract
Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 401-407 |
| Number of pages | 7 |
| Journal | Nature medicine |
| Volume | 24 |
| Issue number | 4 |
| DOIs | |
| State | Published - May 1 2018 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. / Tan, Joshua; Wilder, Brandon; Oyen, David; Zenklusen, Isabelle; Piccoli, Luca; Barbieri, Sonia; Foglierini, Mathilde; Fregni, Chiara Silacci; Marcandalli, Jessica; Jongo, Said; Abdulla, Salim; Perez, Laurent; Corradin, Giampietro; Varani, Luca; Sallusto, Federica; Sim, Betty Kim Lee; Hoffman, Stephen L.; Kappe, Stefan H.I.; Daubenberger, Claudia; Wilson, Ian A.; Lanzavecchia, Antonio.
In: Nature medicine, Vol. 24, No. 4, 01.05.2018, p. 401-407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein
AU - Tan, Joshua
AU - Wilder, Brandon
AU - Oyen, David
AU - Zenklusen, Isabelle
AU - Piccoli, Luca
AU - Barbieri, Sonia
AU - Foglierini, Mathilde
AU - Fregni, Chiara Silacci
AU - Marcandalli, Jessica
AU - Jongo, Said
AU - Abdulla, Salim
AU - Perez, Laurent
AU - Corradin, Giampietro
AU - Varani, Luca
AU - Sallusto, Federica
AU - Sim, Betty Kim Lee
AU - Hoffman, Stephen L.
AU - Kappe, Stefan H.I.
AU - Daubenberger, Claudia
AU - Wilson, Ian A.
AU - Lanzavecchia, Antonio
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.
AB - Immunization with attenuated Plasmodium falciparum sporozoites (PfSPZs) has been shown to be protective against malaria, but the features of the antibody response induced by this treatment remain unclear. To investigate this response in detail, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPZs. All isolated IgG monoclonal antibodies bound to P. falciparum circumsporozoite protein (PfCSP) and recognized distinct epitopes in its N terminus, NANP-repeat region, and C terminus. Strikingly, the most effective antibodies, as determined in a humanized mouse model, bound not only to the repeat region, but also to a minimal peptide at the PfCSP N-terminal junction that is not in the RTS,S vaccine. These dual-specific antibodies were isolated from different donors and were encoded by VH3-30 or VH3-33 alleles that encode tryptophan or arginine at position 52. Using structural and mutational data, we describe the elements required for germline recognition and affinity maturation. Our study provides potent neutralizing antibodies and relevant information for lineage-targeted vaccine design and immunization strategies.
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U2 - 10.1038/nm.4513
DO - 10.1038/nm.4513
M3 - Article
VL - 24
SP - 401
EP - 407
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 4
ER -