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. 2025 Apr 2;17(792):eadq2496.
doi: 10.1126/scitranslmed.adq2496. Epub 2025 Apr 2.

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

Thembi Mdluli  1   2 , Suzanne Wollen-Roberts  1   2 , Mélanie Merbah  1   2 , Bradley Beckman  1   2 , Yifan Li  1   2 , Aljawharah Alrubayyi  1   2 , Daniel J Curtis  1   2 , Zhanna Shubin  1   2 , Michael D Barrera  1   2 , Jacob Boeckelman  1   2 , Shayla Duncan  1   2 , Pallavi Thapa  1   2 , Dohoon Kim  1   2 , Margaret C Costanzo  1   2 , Hongjun Bai  1   2 , Bethany L Dearlove  1   2 , Jay W Hooper  3 , Steven A Kwilas  3 , Dominic Paquin-Proulx  1   2 , Michael A Eller  1   2 , Leigh Anne Eller  1   2 , Hannah Kibuuka  4 , Betty Mwesigwa  4 , Josphat Kosgei  5   6 , Fredrick Sawe  5   6 , Janet Oyieko  5   6 , Nyanda Ntinginya  7 , Joel Mwakisisile  7 , Ilesh Jani  8 , Edna Viegas  8 , Michael Iroezindu  1   9 , Akindiran Akintunde  2   9   10 , Kristopher Paolino  11   12 , Merlin L Robb  1   2 , Lucy Ward  13 , Chelsea McLean  14 , Kerstin Luhn  14 , Cynthia Robinson  14 , Julie A Ake  1 , Morgane Rolland  1   2
Affiliations

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

Thembi Mdluli et al. Sci Transl Med. .

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.

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