Antibodies against West Nile virus nonstructural protein NS1 prevent lethal infection through Fc γ receptor-dependent and -independent mechanisms

Kyung Min Chung, Grant E. Nybakken, Bruce S. Thompson, Michael J. Engle, Anantha Marri, Daved H. Fremont, Michael S. Diamond

Research output: Contribution to journalArticlepeer-review

201 Scopus citations

Abstract

The flavivirus nonstructural protein NS1 is a highly conserved secreted glycoprotein that does not package with the virion. Immunization with NS1 elicits a protective immune response against yellow fever, dengue, and tick-borne encephalitis flaviviruses through poorly defined mechanisms. In this study, we purified a recombinant, secreted form of West Nile virus (WNV) NS1 glycoprotein from baculovirus-infected insect cells and generated 22 new NS1-specific monoclonal antibodies (MAbs). By performing competitive binding assays and expressing truncated NS1 proteins on the surface of yeast (Saccharomyces cerevisiae) and in bacteria, we mapped 21 of the newly generated MAbs to three NS1 fragments. Prophylaxis of C57BL/6 mice with any of four MAbs (10NS1,14NS1,16NS1, and 17NS1) strongly protected against lethal WNV infection (75 to 95% survival, respectively) compared to saline-treated controls (17% survival). In contrast, other anti-NS1 MAbs of the same isotype provided no significant protection. Notably, 14NS1 and 16NS1 also demonstrated marked efficacy as postexposure therapy, even when administered as a single dose 4 days after infection. Virologic analysis showed that 17NS1 protects at an early stage in infection through a C1q-independent and Fc γ receptor-dependent pathway. Interestingly, 14NS1, which maps to a distinct region on NS1, protected through a C1q- and Fc γ receptor-independent mechanism. Overall, our data suggest that distinct regions of NS1 can elicit protective humoral immunity against WNV through different mechanisms.

Original languageEnglish
Pages (from-to)1340-1351
Number of pages12
JournalJournal of virology
Volume80
Issue number3
DOIs
StatePublished - Feb 2006

Fingerprint

Dive into the research topics of 'Antibodies against West Nile virus nonstructural protein NS1 prevent lethal infection through Fc γ receptor-dependent and -independent mechanisms'. Together they form a unique fingerprint.

Cite this