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TitleMapping the antibody response to Lassa virus vaccination of non-human primates.
Journal, issue, pagesEBioMedicine, Vol. 114, Page 105673, Year 2025
Publish dateMar 31, 2025
AuthorsAdrian S Enriquez / Ruben Diaz Avalos / Diptiben Parekh / Christopher L Cooper / Gavin Morrow / Thomas W Geisbert / Christopher L Parks / Kathryn M Hastie / Erica Ollmann Saphire /
PubMed AbstractBACKGROUND: Lassa fever, caused by Lassa virus, is a severe disease, endemic in Western Africa, for which no vaccines or therapeutics are yet approved. Understanding the immune responses elicited by ...BACKGROUND: Lassa fever, caused by Lassa virus, is a severe disease, endemic in Western Africa, for which no vaccines or therapeutics are yet approved. Understanding the immune responses elicited by candidate vaccines is key for approval, including characterisation of antibody epitopes recognised and capacity for neutralisation.
METHODS: Here we used negative-stain electron microscopy polyclonal antibody epitope mapping (EMPEM), in-vitro pseudovirus neutralisation assays, and biophysical antibody competition assays to uncover components of polyclonal antibody responses elicited in nonhuman primates 26 days after receipt of a single immunisation with a fully protective, recombinant, replication-competent vesicular stomatitis virus-based vaccine bearing the Lassa virus glycoprotein GPC.
FINDINGS: Although the vaccinee sera are overall poorly-neutralising, we do directly visualise, within the polyclonal pool, antibodies targeting epitopes on GPC that are consistent with neutralisation, as well as competition with known neutralising mAbs. Nearly every animal, for example, produced antibodies that compete with mAbs against GP1-A and GPC-A neutralising epitopes. The most abundant classes of antibodies, however, are directed against interior interfaces of GPC, while other antibodies recognise post-fusion GPC epitopes not consistent with neutralisation.
INTERPRETATION: It may be that some individual antibodies in the pool are neutralising, but that the abundance of non-neutralising epitopes reduces potency as measured at the polyclonal level. The finding, however, neutralisation-consistent sites and competition with known neutralising antibodies are important steps in vaccine design toward eliciting more potent neutralisation.
FUNDING: A complete list of funding bodies that supported this study is presented in the Funding section.
External linksEBioMedicine / PubMed:40168843
MethodsEM (single particle)
Resolution19.0 - 20.0 Å
Structure data

EMDB-46683: Polyclonal Immune Complex of Fab binding the Lassa Virus Glycoprotein from serum of Subject-5 at Day 26
Method: EM (single particle) / Resolution: 19.0 Å

EMDB-46766: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-8 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46784: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-8 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46809: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-13 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46810: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-11 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46817: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-11 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46851: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46852: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46863: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46864: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46865: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46866: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-9 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46882: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46883: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46886: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46887: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46889: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46890: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46891: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-12 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46964: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46965: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-46966: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47059: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47060: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47062: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47063: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47064: Immune complex of Lassa virus glycoprotein (Josiah) with polyclonal Fab from Subject-7 at Day 26
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-47065: Immune complex of Lassa virus glycoprotein (Josiah)
Method: EM (single particle) / Resolution: 20.0 Å

Source
  • Lassa virus Josiah
  • Macaca fascicularis (crab-eating macaque)

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