TY - JOUR
T1 - Antibodies targeting epitopes on the cell-surface form of NS1 protect against Zika virus infection during pregnancy
AU - Wessel, Alex W.
AU - Kose, Nurgun
AU - Bombardi, Robin G.
AU - Roy, Vicky
AU - Chantima, Warangkana
AU - Mongkolsapaya, Juthathip
AU - Edeling, Melissa A.
AU - Nelson, Christopher A.
AU - Bosch, Irene
AU - Alter, Galit
AU - Screaton, Gavin R.
AU - Fremont, David H.
AU - Crowe, James E.
AU - Diamond, Michael S.
N1 - Funding Information:
This study was supported by NIH grants R01 AI073755 and 75N93019C00062, and contract HHSN272201400058C and HHSN272201700060C. A.W.W. was supported by an NIH pre-doctoral training grant award (T32 5T32AI007172-38). G.R.S. was supported by the Wellcome Trust, UK (grants no. 095541/Z/11/Z and 203224/Z/16/Z). G.R.S is a Wellcome Trust Senior Investigator. We thank Rachel Nargi, Rachel Sutton, Erica Armstrong, and Robert Carnahan of Vanderbilt for preparation of recombinant human antibodies.
Funding Information:
M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, Carnival Corporation and on the Scientific Advisory Board of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi-Aventis., Pfizer, and Novavax, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines, and is the founder of IDBiologics. G.R.S. is on the Scientific Advisory Board for GSK Vaccines. G.A. is a founder of Systems Seromyx Inc. The Alter laboratory has received funding from Janssen, Merck, Sanofi, Pfizer, GlaxoSmithKline, Bristol Myers Squibb, and Gilead. All other authors declare no competing interests.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.
AB - There are no licensed therapeutics or vaccines available against Zika virus (ZIKV) to counteract its potential for congenital disease. Antibody-based countermeasures targeting the ZIKV envelope protein have been hampered by concerns for cross-reactive responses that induce antibody-dependent enhancement (ADE) of heterologous flavivirus infection. Nonstructural protein 1 (NS1) is a membrane-associated and secreted glycoprotein that functions in flavivirus replication and immune evasion but is absent from the virion. Although some studies suggest that antibodies against ZIKV NS1 are protective, their activity during congenital infection is unknown. Here we develop mouse and human anti-NS1 monoclonal antibodies that protect against ZIKV in both non-pregnant and pregnant mice. Avidity of antibody binding to cell-surface NS1 along with Fc effector functions engagement correlate with protection in vivo. Protective mAbs map to exposed epitopes in the wing domain and loop face of the β-platform. Anti-NS1 antibodies provide an alternative strategy for protection against congenital ZIKV infection without causing ADE.
UR - http://www.scopus.com/inward/record.url?scp=85092785339&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-19096-y
DO - 10.1038/s41467-020-19096-y
M3 - Article
C2 - 33077712
AN - SCOPUS:85092785339
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5278
ER -