Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages
Megan L. Heinrich, Matthew L. Boisen, Diana K. S. Nelson, Duane J. Bush, Robert W. Cross, Anatoliy Koval, Andrew R. Hoffmann, Brandon J. Beddingfield, Kathryn M. Hastie, Megan M. Rowland, Irina Aimukanova, Sophia A. Koval, Raju Lathigra, Viktoriya Borisevich, Mambu Momoh, John Demby Sandi, Augustine Goba, lkponmwosa Odia, Francis Baimba, John Aiyepada, Benevolence Ebo, Philomena Eromon, Chinedu Ugwu, Onikepe Folarin, Testimony Olumade, Macdonald Nonso Onyechi, Johnson Etafo, Rashidat Adeyemi, E. E. Ella, Maryam Aminu, Simji Samuel Gomerep, Matthew Afam Eke, Olusola Ogunsanya, George O. Akpede, Danny Asogun, Sylvanus Okogbenin, Peter O. Okokhere, Johan Holst, Jeffrey G. Shaffer, John S. Schieffelin, Thomas W. Geisbert, Erica Ollmann Saphire, Christian Happi, Donald S. Grant, Robert F. Garry, Luis M. Branco
Abstract
Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.