Risk of Zika microcephaly correlates with features of maternal antibodies

Davide F. Robbiani; Priscilla C. Olsen; Federico Costa; Qiao Wang; Thiago Y. Oliveira; Nivison Nery; Adeolu Aromolaran; Mateus S. do Rosário; Gielson A. Sacramento; Jaqueline S. Cruz; Ricardo Khouri; Elsio A. Wunder; Adriana Mattos; Bruno de Paula Freitas; Manoel Sarno; Gracinda Archanjo; Dina Daltro; Gustavo B.S. Carvalho; Kleber Pimentel; Isadora C. de Siqueira; João R.M. de Almeida; Daniele F. Henriques; Juliana A. Lima; Pedro F.C. Vasconcelos; Dennis Schaefer-Babajew; Stephanie A. Azzopardi; Leonia Bozzacco; Anna Gazumyan; Rubens Belfort; Ana P. Alcântara; Gustavo Carvalho; Licia Moreira; Katiaci Araujo; Mitermayer G. Reis; Rebekah I. Keesler; Lark L. Coffey; Jennifer Tisoncik-Go; Michael Gale; Lakshmi Rajagopal; Kristina M. Adams Waldorf; Dawn M. Dudley; Heather A. Simmons; Andres Mejia; David H. O’Connor; Rosemary J. Steinbach; Nicole Haese; Jessica Smith; Anne Lewis; Lois Colgin; Victoria Roberts; Antonio Frias; Meredith Kelleher; Alec Hirsch; Daniel N. Streblow; Charles M. Rice; Margaret R. MacDonald; Antonio R.P. de Almeida; Koen K.A. van Rompay; Albert I. Ko; Michel C. Nussenzweig

doi:10.1084/jem.20191061

Risk of Zika microcephaly correlates with features of maternal antibodies

Davide F. Robbiani, Priscilla C. Olsen, Federico Costa, Qiao Wang, Thiago Y. Oliveira, Nivison Nery, Adeolu Aromolaran, Mateus S. do Rosário, Gielson A. Sacramento, Jaqueline S. Cruz, Ricardo Khouri, Elsio A. Wunder, Adriana Mattos, Bruno de Paula Freitas, Manoel Sarno, Gracinda Archanjo, Dina Daltro, Gustavo B.S. Carvalho, Kleber Pimentel, Isadora C. de SiqueiraJoão R.M. de Almeida, Daniele F. Henriques, Juliana A. Lima, Pedro F.C. Vasconcelos, Dennis Schaefer-Babajew, Stephanie A. Azzopardi, Leonia Bozzacco, Anna Gazumyan, Rubens Belfort, Ana P. Alcântara, Gustavo Carvalho, Licia Moreira, Katiaci Araujo, Mitermayer G. Reis, Rebekah I. Keesler, Lark L. Coffey, Jennifer Tisoncik-Go, Michael Gale, Lakshmi Rajagopal, Kristina M. Adams Waldorf, Dawn M. Dudley, Heather A. Simmons, Andres Mejia, David H. O’Connor, Rosemary J. Steinbach, Nicole Haese, Jessica Smith, Anne Lewis, Lois Colgin, Victoria Roberts, Antonio Frias, Meredith Kelleher, Alec Hirsch, Daniel N. Streblow, Charles M. Rice, Margaret R. MacDonald, Antonio R.P. de Almeida, Koen K.A. van Rompay, Albert I. Ko, Michel C. Nussenzweig

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

Original language	English (US)
Pages (from-to)	2302-2315
Number of pages	14
Journal	Journal of Experimental Medicine
Volume	216
Issue number	10
DOIs	https://doi.org/10.1084/jem.20191061
State	Published - Oct 1 2019

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1084/jem.20191061

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Robbiani, D. F., Olsen, P. C., Costa, F., Wang, Q., Oliveira, T. Y., Nery, N., Aromolaran, A., do Rosário, M. S., Sacramento, G. A., Cruz, J. S., Khouri, R., Wunder, E. A., Mattos, A., de Paula Freitas, B., Sarno, M., Archanjo, G., Daltro, D., Carvalho, G. B. S., Pimentel, K., ... Nussenzweig, M. C. (2019). Risk of Zika microcephaly correlates with features of maternal antibodies. Journal of Experimental Medicine, 216(10), 2302-2315. https://doi.org/10.1084/jem.20191061

Robbiani, DF, Olsen, PC, Costa, F, Wang, Q, Oliveira, TY, Nery, N, Aromolaran, A, do Rosário, MS, Sacramento, GA, Cruz, JS, Khouri, R, Wunder, EA, Mattos, A, de Paula Freitas, B, Sarno, M, Archanjo, G, Daltro, D, Carvalho, GBS, Pimentel, K, de Siqueira, IC, de Almeida, JRM, Henriques, DF, Lima, JA, Vasconcelos, PFC, Schaefer-Babajew, D, Azzopardi, SA, Bozzacco, L, Gazumyan, A, Belfort, R, Alcântara, AP, Carvalho, G, Moreira, L, Araujo, K, Reis, MG, Keesler, RI, Coffey, LL, Tisoncik-Go, J, Gale, M, Rajagopal, L, Adams Waldorf, KM, Dudley, DM, Simmons, HA, Mejia, A, O’Connor, DH, Steinbach, RJ, Haese, N, Smith, J , Lewis, A , Colgin, L, Roberts, V, Frias, A , Kelleher, M , Hirsch, A , Streblow, DN, Rice, CM, MacDonald, MR, de Almeida, ARP, van Rompay, KKA, Ko, AI & Nussenzweig, MC 2019, 'Risk of Zika microcephaly correlates with features of maternal antibodies', Journal of Experimental Medicine, vol. 216, no. 10, pp. 2302-2315. https://doi.org/10.1084/jem.20191061

@article{da922019bdc14761908143f4dd2a855e,

title = "Risk of Zika microcephaly correlates with features of maternal antibodies",

abstract = "Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.",

author = "Robbiani, {Davide F.} and Olsen, {Priscilla C.} and Federico Costa and Qiao Wang and Oliveira, {Thiago Y.} and Nivison Nery and Adeolu Aromolaran and {do Ros{\'a}rio}, {Mateus S.} and Sacramento, {Gielson A.} and Cruz, {Jaqueline S.} and Ricardo Khouri and Wunder, {Elsio A.} and Adriana Mattos and {de Paula Freitas}, Bruno and Manoel Sarno and Gracinda Archanjo and Dina Daltro and Carvalho, {Gustavo B.S.} and Kleber Pimentel and {de Siqueira}, {Isadora C.} and {de Almeida}, {Jo{\~a}o R.M.} and Henriques, {Daniele F.} and Lima, {Juliana A.} and Vasconcelos, {Pedro F.C.} and Dennis Schaefer-Babajew and Azzopardi, {Stephanie A.} and Leonia Bozzacco and Anna Gazumyan and Rubens Belfort and Alc{\^a}ntara, {Ana P.} and Gustavo Carvalho and Licia Moreira and Katiaci Araujo and Reis, {Mitermayer G.} and Keesler, {Rebekah I.} and Coffey, {Lark L.} and Jennifer Tisoncik-Go and Michael Gale and Lakshmi Rajagopal and {Adams Waldorf}, {Kristina M.} and Dudley, {Dawn M.} and Simmons, {Heather A.} and Andres Mejia and O{\textquoteright}Connor, {David H.} and Steinbach, {Rosemary J.} and Nicole Haese and Jessica Smith and Anne Lewis and Lois Colgin and Victoria Roberts and Antonio Frias and Meredith Kelleher and Alec Hirsch and Streblow, {Daniel N.} and Rice, {Charles M.} and MacDonald, {Margaret R.} and {de Almeida}, {Antonio R.P.} and {van Rompay}, {Koen K.A.} and Ko, {Albert I.} and Nussenzweig, {Michel C.}",

note = "Funding Information: This work was supported by National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O{\textquoteright}Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded to WNPRC, at a facility constructed in part with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de De-senvolvimento Cientifico e Tecnol{\'o}gico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel Superior (Zika fast-track). P.C. Olsen is supported by the Pew Latin American Fellows Program in the Biomedical Sciences. D. Schaefer-Babajew is supported by Studienstiftung des Deutschen Volkes. F. Costa is a Wellcome Trust Fellow in Public Health and Tropical Medicine, and M.C. Nussenzweig is a Howard Hughes Medical Institute Investigator. Funding Information: This work was supported by National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Funda??o de Amparo ? Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O?Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded to WNPRC, at a facility constructed in part with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnol?gico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Zika fast-track). P.C. Olsen is supported by the Pew Latin American Fellows Program in the Biomedical Sciences. D. Schaefer-Babajew is supported by Studienstiftung des Deutschen Volkes. F. Costa is a Wellcome Trust Fellow in Public Health and Tropical Medicine, and M.C. Nussenzweig is a Howard Hughes Medical Institute Investigator. Publisher Copyright: {\textcopyright} 2019 Robbiani et al.",

year = "2019",

month = oct,

day = "1",

doi = "10.1084/jem.20191061",

language = "English (US)",

volume = "216",

pages = "2302--2315",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "10",

}

TY - JOUR

T1 - Risk of Zika microcephaly correlates with features of maternal antibodies

AU - Robbiani, Davide F.

AU - Olsen, Priscilla C.

AU - Costa, Federico

AU - Wang, Qiao

AU - Oliveira, Thiago Y.

AU - Nery, Nivison

AU - Aromolaran, Adeolu

AU - do Rosário, Mateus S.

AU - Sacramento, Gielson A.

AU - Cruz, Jaqueline S.

AU - Khouri, Ricardo

AU - Wunder, Elsio A.

AU - Mattos, Adriana

AU - de Paula Freitas, Bruno

AU - Sarno, Manoel

AU - Archanjo, Gracinda

AU - Daltro, Dina

AU - Carvalho, Gustavo B.S.

AU - Pimentel, Kleber

AU - de Siqueira, Isadora C.

AU - de Almeida, João R.M.

AU - Henriques, Daniele F.

AU - Lima, Juliana A.

AU - Vasconcelos, Pedro F.C.

AU - Schaefer-Babajew, Dennis

AU - Azzopardi, Stephanie A.

AU - Bozzacco, Leonia

AU - Gazumyan, Anna

AU - Belfort, Rubens

AU - Alcântara, Ana P.

AU - Carvalho, Gustavo

AU - Moreira, Licia

AU - Araujo, Katiaci

AU - Reis, Mitermayer G.

AU - Keesler, Rebekah I.

AU - Coffey, Lark L.

AU - Tisoncik-Go, Jennifer

AU - Gale, Michael

AU - Rajagopal, Lakshmi

AU - Adams Waldorf, Kristina M.

AU - Dudley, Dawn M.

AU - Simmons, Heather A.

AU - Mejia, Andres

AU - O’Connor, David H.

AU - Steinbach, Rosemary J.

AU - Haese, Nicole

AU - Smith, Jessica

AU - Lewis, Anne

AU - Colgin, Lois

AU - Roberts, Victoria

AU - Frias, Antonio

AU - Kelleher, Meredith

AU - Hirsch, Alec

AU - Streblow, Daniel N.

AU - Rice, Charles M.

AU - MacDonald, Margaret R.

AU - de Almeida, Antonio R.P.

AU - van Rompay, Koen K.A.

AU - Ko, Albert I.

AU - Nussenzweig, Michel C.

N1 - Funding Information: This work was supported by National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Fundação de Amparo à Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O’Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded to WNPRC, at a facility constructed in part with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de De-senvolvimento Cientifico e Tecnológico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Zika fast-track). P.C. Olsen is supported by the Pew Latin American Fellows Program in the Biomedical Sciences. D. Schaefer-Babajew is supported by Studienstiftung des Deutschen Volkes. F. Costa is a Wellcome Trust Fellow in Public Health and Tropical Medicine, and M.C. Nussenzweig is a Howard Hughes Medical Institute Investigator. Funding Information: This work was supported by National Institutes of Health grants 5R01AI121207, R01TW009504, and R25TW009338 to A.I. Ko; National Institutes of Health pilot awards U19AI111825 and UL1TR001866 to D.F. Robbiani; National Institutes of Health grants R01AI037526, UM1AI100663, U19AI111825, UL1TR001866, and P01AI138938 to M.C. Nussenzweig; National Institutes of Health grants R01AI124690 and U19AI057229 (Cooperative Center for Human Immunology pilot project); The Rockefeller University Development Office and anonymous donors (to C.M. Rice); Funda??o de Amparo ? Pesquisa do Estado da Bahia grant PET0021/2016 (to M.G. Reis); National Institutes of Health grant R21AI129479-Supplement (to K.K.A. Van Rompay) and the National Institutes of Health Office of Research Infrastructure Programs/OD (P51OD011107 to the CNPRC); the United States Food and Drug Administration contract HHSF223201610542P (to L.L. Coffey); National Institutes of Health grants R01AI100989 and R01AI133976 (to L. Rajagopal and K.M. Adams Waldorf); and National Institutes of Health grants AI083019 and AI104002 (to M. Gale Jr.) and grant P51OD010425 to the WaNPRC (to K.M. Adams Waldorf, J. Tisoncik-Go, and M. Gale Jr.). Studies at WNPRC were supported by DHHS/PHS/National Institutes of Health grant R01Al116382-01A1 (to D.H. O?Connor), in part by the National Institutes of Health Office of Research Infrastructure Programs/OD (grant P51OD011106) awarded to WNPRC, at a facility constructed in part with support from Research Facilities Improvement Program grants RR15459-01 and RR020141-01; and National Institutes of Health core and pilot grant P51 OD011092 and grants R21-HD091032 and R01-HD08633 (to ONPRC). P.F.C. Vasconcelos was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnol?gico (projects 303999/2016-0, 439971/20016-0, and 440405/2016-5) and Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (Zika fast-track). P.C. Olsen is supported by the Pew Latin American Fellows Program in the Biomedical Sciences. D. Schaefer-Babajew is supported by Studienstiftung des Deutschen Volkes. F. Costa is a Wellcome Trust Fellow in Public Health and Tropical Medicine, and M.C. Nussenzweig is a Howard Hughes Medical Institute Investigator. Publisher Copyright: © 2019 Robbiani et al.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

AB - Zika virus (ZIKV) infection during pregnancy causes congenital abnormalities, including microcephaly. However, rates vary widely, and the contributing risk factors remain unclear. We examined the serum antibody response to ZIKV and other flaviviruses in Brazilian women giving birth during the 2015–2016 outbreak. Infected pregnancies with intermediate or higher ZIKV antibody enhancement titers were at increased risk to give birth to microcephalic infants compared with those with lower titers (P < 0.0001). Similarly, analysis of ZIKV-infected pregnant macaques revealed that fetal brain damage was more frequent in mothers with higher enhancement titers. Thus, features of the maternal antibodies are associated with and may contribute to the genesis of ZIKV-associated microcephaly.

UR - http://www.scopus.com/inward/record.url?scp=85072993593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072993593&partnerID=8YFLogxK

U2 - 10.1084/jem.20191061

DO - 10.1084/jem.20191061

M3 - Article

C2 - 31413072

AN - SCOPUS:85072993593

SN - 0022-1007

VL - 216

SP - 2302

EP - 2315

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 10

ER -

Risk of Zika microcephaly correlates with features of maternal antibodies

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