Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses

Thembi Mdluli; Suzanne Wollen-Roberts; Mélanie Merbah; Bradley Beckman; Yifan Li; Aljawharah Alrubayyi; Daniel J. Curtis; Zhanna Shubin; Michael D. Barrera; Jacob Boeckelman; Shayla Duncan; Pallavi Thapa; Dohoon Kim; Margaret C. Costanzo; Hongjun Bai; Bethany L. Dearlove; Jay W. Hooper; Steven A. Kwilas; Dominic Paquin-Proulx; Michael A. Eller; Leigh Anne Eller; Hannah Kibuuka; Betty Mwesigwa; Josphat Kosgei; Fredrick Sawe; Janet Oyieko; Nyanda Ntinginya; Joel Mwakisisile; Ilesh Jani; Edna Viegas; Michael Iroezindu; Akindiran Akintunde; Kristopher Paolino; Merlin L. Robb; Lucy Ward; Chelsea McLean; Kerstin Luhn; Cynthia Robinson; Julie A. Ake; Morgane Rolland

doi:10.1126/scitranslmed.adq2496

Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses

Thembi Mdluli, Suzanne Wollen-Roberts, Mélanie Merbah, Bradley Beckman, Yifan Li, Aljawharah Alrubayyi, Daniel J. Curtis, Zhanna Shubin, Michael D. Barrera, Jacob Boeckelman, Shayla Duncan, Pallavi Thapa, Dohoon Kim, Margaret C. Costanzo, Hongjun Bai, Bethany L. Dearlove, Jay W. Hooper, Steven A. Kwilas, Dominic Paquin-Proulx, Michael A. EllerLeigh Anne Eller, Hannah Kibuuka, Betty Mwesigwa, Josphat Kosgei, Fredrick Sawe, Janet Oyieko, Nyanda Ntinginya, Joel Mwakisisile, Ilesh Jani, Edna Viegas, Michael Iroezindu, Akindiran Akintunde, Kristopher Paolino, Merlin L. Robb, Lucy Ward, Chelsea McLean, Kerstin Luhn, Cynthia Robinson, Julie A. Ake, Morgane Rolland^*

^*Corresponding author for this work

Medicine

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

3 Scopus citations

Abstract

The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first. The response to vaccination was EBOV GP specific and defined by high antibody binding, Fc effector, and neutralizing responses with CD4 T cell responses also contributing. The vaccine-induced antibody profile did not distinguish people living with or without HIV-1. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses.

Original language	English
Article number	eadq2496
Journal	Science Translational Medicine
Volume	17
Issue number	792
DOIs	https://doi.org/10.1126/scitranslmed.adq2496
State	Published - 2 Apr 2025

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10.1126/scitranslmed.adq2496

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Mdluli, T., Wollen-Roberts, S., Merbah, M., Beckman, B., Li, Y., Alrubayyi, A., Curtis, D. J., Shubin, Z., Barrera, M. D., Boeckelman, J., Duncan, S., Thapa, P., Kim, D., Costanzo, M. C., Bai, H., Dearlove, B. L., Hooper, J. W., Kwilas, S. A., Paquin-Proulx, D., ... Rolland, M. (2025). Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses. Science Translational Medicine, 17(792), Article eadq2496. https://doi.org/10.1126/scitranslmed.adq2496

@article{b03bcafa17194ca0a134c41ebf666bd6,

title = "Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses",

abstract = "The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first. The response to vaccination was EBOV GP specific and defined by high antibody binding, Fc effector, and neutralizing responses with CD4 T cell responses also contributing. The vaccine-induced antibody profile did not distinguish people living with or without HIV-1. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses.",

author = "Thembi Mdluli and Suzanne Wollen-Roberts and M{\'e}lanie Merbah and Bradley Beckman and Yifan Li and Aljawharah Alrubayyi and Curtis, {Daniel J.} and Zhanna Shubin and Barrera, {Michael D.} and Jacob Boeckelman and Shayla Duncan and Pallavi Thapa and Dohoon Kim and Costanzo, {Margaret C.} and Hongjun Bai and Dearlove, {Bethany L.} and Hooper, {Jay W.} and Kwilas, {Steven A.} and Dominic Paquin-Proulx and Eller, {Michael A.} and Eller, {Leigh Anne} and Hannah Kibuuka and Betty Mwesigwa and Josphat Kosgei and Fredrick Sawe and Janet Oyieko and Nyanda Ntinginya and Joel Mwakisisile and Ilesh Jani and Edna Viegas and Michael Iroezindu and Akindiran Akintunde and Kristopher Paolino and Robb, {Merlin L.} and Lucy Ward and Chelsea McLean and Kerstin Luhn and Cynthia Robinson and Ake, {Julie A.} and Morgane Rolland",

note = "Publisher Copyright: copyright {\textcopyright} 2025 The Authors, some rights reserved.",

year = "2025",

month = apr,

day = "2",

doi = "10.1126/scitranslmed.adq2496",

language = "English",

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Mdluli, T, Wollen-Roberts, S, Merbah, M, Beckman, B, Li, Y, Alrubayyi, A, Curtis, DJ, Shubin, Z, Barrera, MD, Boeckelman, J, Duncan, S, Thapa, P, Kim, D, Costanzo, MC, Bai, H, Dearlove, BL, Hooper, JW, Kwilas, SA, Paquin-Proulx, D, Eller, MA, Eller, LA, Kibuuka, H, Mwesigwa, B, Kosgei, J, Sawe, F, Oyieko, J, Ntinginya, N, Mwakisisile, J, Jani, I, Viegas, E, Iroezindu, M, Akintunde, A, Paolino, K, Robb, ML, Ward, L, McLean, C, Luhn, K, Robinson, C, Ake, JA & Rolland, M 2025, 'Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses', Science Translational Medicine, vol. 17, no. 792, eadq2496. https://doi.org/10.1126/scitranslmed.adq2496

TY - JOUR

T1 - Ebola virus vaccination elicits Ebola virus–specific immune responses without substantial cross-reactivity to other filoviruses

AU - Mdluli, Thembi

AU - Wollen-Roberts, Suzanne

AU - Merbah, Mélanie

AU - Beckman, Bradley

AU - Li, Yifan

AU - Alrubayyi, Aljawharah

AU - Curtis, Daniel J.

AU - Shubin, Zhanna

AU - Barrera, Michael D.

AU - Boeckelman, Jacob

AU - Duncan, Shayla

AU - Thapa, Pallavi

AU - Kim, Dohoon

AU - Costanzo, Margaret C.

AU - Bai, Hongjun

AU - Dearlove, Bethany L.

AU - Hooper, Jay W.

AU - Kwilas, Steven A.

AU - Paquin-Proulx, Dominic

AU - Eller, Michael A.

AU - Eller, Leigh Anne

AU - Kibuuka, Hannah

AU - Mwesigwa, Betty

AU - Kosgei, Josphat

AU - Sawe, Fredrick

AU - Oyieko, Janet

AU - Ntinginya, Nyanda

AU - Mwakisisile, Joel

AU - Jani, Ilesh

AU - Viegas, Edna

AU - Iroezindu, Michael

AU - Akintunde, Akindiran

AU - Paolino, Kristopher

AU - Robb, Merlin L.

AU - Ward, Lucy

AU - McLean, Chelsea

AU - Luhn, Kerstin

AU - Robinson, Cynthia

AU - Ake, Julie A.

AU - Rolland, Morgane

PY - 2025/4/2

Y1 - 2025/4/2

N2 - The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first. The response to vaccination was EBOV GP specific and defined by high antibody binding, Fc effector, and neutralizing responses with CD4 T cell responses also contributing. The vaccine-induced antibody profile did not distinguish people living with or without HIV-1. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses.

AB - The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. We conducted a systems immunology analysis of antibody-mediated and cellular immune responses induced after two immunizations with either vaccine used first. The response to vaccination was EBOV GP specific and defined by high antibody binding, Fc effector, and neutralizing responses with CD4 T cell responses also contributing. The vaccine-induced antibody profile did not distinguish people living with or without HIV-1. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses.

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DO - 10.1126/scitranslmed.adq2496

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