Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials

Myra Happe; Amelia R. Hofstetter; Jing Wang; Galina V. Yamshchikov; La Sonji A. Holman; Laura Novik; Larisa Strom; Francis Kiweewa; Salim Wakabi; Monica Millard; Colleen F. Kelley; Sarah Kabbani; Srilatha Edupuganti; Allison Beck; Florence Kaltovich; Tamar Murray; Susanna Tsukerman; Derick Carr; Carl Ashman; Daphne A. Stanley; Aurélie Ploquin; Robert T. Bailer; Richard Schwartz; Fatim Cham; Allan Tindikahwa; Zonghui Hu; Ingelise J. Gordon; Nadine Rouphael; Katherine V. Houser; Emily E. Coates; Barney S. Graham; Richard A. Koup; John R. Mascola; Nancy J. Sullivan; Merlin L. Robb; Julie A. Ake; Kirsten E. Lyke; Mark J. Mulligan; Julie E. Ledgerwood; Hannah Kibuuka; Joseph P. Casazza; Grace L. Chen; Mary E. Enama; Martin R. Gaudinski; Cynthia Starr Hendel; Pamela J.M. Costner; Brenda Larkin; Floreliz Mendoza; Jamie Sanders; William R. Whalen; Kathryn L. Zephir; Judith Straling; Hope DeCederfelt; Michelle Conan-Cibotti; Judy Stein; Iris R. Pittman; Olga Vasilenko; Adam DeZure; Sandra Sitar; Lesia K. Dropulic; Sarah H. Plummer; Thuy A. Nguyen; Nina M. Berkowitz; Nancy Greenberg; Lisa Chrisley; Melissa Billington; Xiaolin Wang; Jo Anna Becker; James D. Campbell; Wilbur H. Chen; Alyson Kwon; Brenda Dorsey; Jennifer Courneya; Panagiota Komninou; Myounghee Lee; Mary Bower; Charles A. Bailey; Wendy Nesheim; Tigisty Girmay; Jianguo Xu; Melinda Ogilvie; Joann Sadowski; Eileen Osinski; Lilin Lai; Vicki Grimes; Moses R. Kamya; Nelson L. Michael; Francis Kajumba; Jinantat Ananworanich; Betty Mwesigwa; Geofrey Kimbugne; Kenneth Luzinda; Immaculate Nakabuye; Maureen G. Mukyala; Mable Kabahubya; Lydia Nakibuuka; Robinah Matovu

doi:10.1038/s41541-024-00833-z

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials

Myra Happe^*, Amelia R. Hofstetter, Jing Wang, Galina V. Yamshchikov, La Sonji A. Holman, Laura Novik, Larisa Strom, Francis Kiweewa, Salim Wakabi, Monica Millard, Colleen F. Kelley, Sarah Kabbani, Srilatha Edupuganti, Allison Beck, Florence Kaltovich, Tamar Murray, Susanna Tsukerman, Derick Carr, Carl Ashman, Daphne A. StanleyAurélie Ploquin, Robert T. Bailer, Richard Schwartz, Fatim Cham, Allan Tindikahwa, Zonghui Hu, Ingelise J. Gordon, Nadine Rouphael, Katherine V. Houser, Emily E. Coates, Barney S. Graham, Richard A. Koup, John R. Mascola, Nancy J. Sullivan, Merlin L. Robb, Julie A. Ake, Kirsten E. Lyke, Mark J. Mulligan, Julie E. Ledgerwood, Hannah Kibuuka, Joseph P. Casazza, Grace L. Chen, Mary E. Enama, Martin R. Gaudinski, Cynthia Starr Hendel, Pamela J.M. Costner, Brenda Larkin, Floreliz Mendoza, Jamie Sanders, William R. Whalen, Kathryn L. Zephir, Judith Straling, Hope DeCederfelt, Michelle Conan-Cibotti, Judy Stein, Iris R. Pittman, Olga Vasilenko, Adam DeZure, Sandra Sitar, Lesia K. Dropulic, Sarah H. Plummer, Thuy A. Nguyen, Nina M. Berkowitz, Nancy Greenberg, Lisa Chrisley, Melissa Billington, Xiaolin Wang, Jo Anna Becker, James D. Campbell, Wilbur H. Chen, Alyson Kwon, Brenda Dorsey, Jennifer Courneya, Panagiota Komninou, Myounghee Lee, Mary Bower, Charles A. Bailey, Wendy Nesheim, Tigisty Girmay, Jianguo Xu, Melinda Ogilvie, Joann Sadowski, Eileen Osinski, Lilin Lai, Vicki Grimes, Moses R. Kamya, Nelson L. Michael, Francis Kajumba, Jinantat Ananworanich, Betty Mwesigwa, Geofrey Kimbugne, Kenneth Luzinda, Immaculate Nakabuye, Maureen G. Mukyala, Mable Kabahubya, Lydia Nakibuuka, Robinah Matovu

^*Corresponding author for this work

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

Abstract

Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

Original language	English
Article number	67
Journal	npj Vaccines
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41541-024-00833-z
State	Published - Dec 2024
Externally published	Yes

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Happe, M., Hofstetter, A. R., Wang, J., Yamshchikov, G. V., Holman, L. S. A., Novik, L., Strom, L., Kiweewa, F., Wakabi, S., Millard, M., Kelley, C. F., Kabbani, S., Edupuganti, S., Beck, A., Kaltovich, F., Murray, T., Tsukerman, S., Carr, D., Ashman, C., ... Matovu, R. (2024). Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials. npj Vaccines, 9(1), Article 67. https://doi.org/10.1038/s41541-024-00833-z

@article{e35655793c734de2a9d2590e11fdfb26,

title = "Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials",

abstract = "Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-na{\"i}ve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-na{\"i}ve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.",

author = "Myra Happe and Hofstetter, {Amelia R.} and Jing Wang and Yamshchikov, {Galina V.} and Holman, {La Sonji A.} and Laura Novik and Larisa Strom and Francis Kiweewa and Salim Wakabi and Monica Millard and Kelley, {Colleen F.} and Sarah Kabbani and Srilatha Edupuganti and Allison Beck and Florence Kaltovich and Tamar Murray and Susanna Tsukerman and Derick Carr and Carl Ashman and Stanley, {Daphne A.} and Aur{\'e}lie Ploquin and Bailer, {Robert T.} and Richard Schwartz and Fatim Cham and Allan Tindikahwa and Zonghui Hu and Gordon, {Ingelise J.} and Nadine Rouphael and Houser, {Katherine V.} and Coates, {Emily E.} and Graham, {Barney S.} and Koup, {Richard A.} and Mascola, {John R.} and Sullivan, {Nancy J.} and Robb, {Merlin L.} and Ake, {Julie A.} and Lyke, {Kirsten E.} and Mulligan, {Mark J.} and Ledgerwood, {Julie E.} and Hannah Kibuuka and Casazza, {Joseph P.} and Chen, {Grace L.} and Enama, {Mary E.} and Gaudinski, {Martin R.} and Hendel, {Cynthia Starr} and Costner, {Pamela J.M.} and Brenda Larkin and Floreliz Mendoza and Jamie Sanders and Whalen, {William R.} and Zephir, {Kathryn L.} and Judith Straling and Hope DeCederfelt and Michelle Conan-Cibotti and Judy Stein and Pittman, {Iris R.} and Olga Vasilenko and Adam DeZure and Sandra Sitar and Dropulic, {Lesia K.} and Plummer, {Sarah H.} and Nguyen, {Thuy A.} and Berkowitz, {Nina M.} and Nancy Greenberg and Lisa Chrisley and Melissa Billington and Xiaolin Wang and Becker, {Jo Anna} and Campbell, {James D.} and Chen, {Wilbur H.} and Alyson Kwon and Brenda Dorsey and Jennifer Courneya and Panagiota Komninou and Myounghee Lee and Mary Bower and Bailey, {Charles A.} and Wendy Nesheim and Tigisty Girmay and Jianguo Xu and Melinda Ogilvie and Joann Sadowski and Eileen Osinski and Lilin Lai and Vicki Grimes and Kamya, {Moses R.} and Michael, {Nelson L.} and Francis Kajumba and Jinantat Ananworanich and Betty Mwesigwa and Geofrey Kimbugne and Kenneth Luzinda and Immaculate Nakabuye and Mukyala, {Maureen G.} and Mable Kabahubya and Lydia Nakibuuka and Robinah Matovu",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41541-024-00833-z",

language = "English",

volume = "9",

journal = "npj Vaccines",

issn = "2059-0105",

number = "1",

}

Happe, M, Hofstetter, AR, Wang, J, Yamshchikov, GV, Holman, LSA, Novik, L, Strom, L, Kiweewa, F, Wakabi, S, Millard, M, Kelley, CF, Kabbani, S, Edupuganti, S, Beck, A, Kaltovich, F, Murray, T, Tsukerman, S, Carr, D, Ashman, C, Stanley, DA, Ploquin, A, Bailer, RT, Schwartz, R, Cham, F, Tindikahwa, A, Hu, Z, Gordon, IJ, Rouphael, N, Houser, KV, Coates, EE, Graham, BS, Koup, RA, Mascola, JR, Sullivan, NJ, Robb, ML, Ake, JA, Lyke, KE, Mulligan, MJ, Ledgerwood, JE, Kibuuka, H, Casazza, JP, Chen, GL, Enama, ME, Gaudinski, MR, Hendel, CS, Costner, PJM, Larkin, B, Mendoza, F, Sanders, J, Whalen, WR, Zephir, KL, Straling, J, DeCederfelt, H, Conan-Cibotti, M, Stein, J, Pittman, IR, Vasilenko, O, DeZure, A, Sitar, S, Dropulic, LK, Plummer, SH, Nguyen, TA, Berkowitz, NM, Greenberg, N, Chrisley, L, Billington, M, Wang, X, Becker, JA, Campbell, JD, Chen, WH, Kwon, A, Dorsey, B, Courneya, J, Komninou, P, Lee, M, Bower, M, Bailey, CA, Nesheim, W, Girmay, T, Xu, J, Ogilvie, M, Sadowski, J, Osinski, E, Lai, L, Grimes, V, Kamya, MR, Michael, NL, Kajumba, F, Ananworanich, J, Mwesigwa, B, Kimbugne, G, Luzinda, K, Nakabuye, I, Mukyala, MG, Kabahubya, M, Nakibuuka, L & Matovu, R 2024, 'Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials', npj Vaccines, vol. 9, no. 1, 67. https://doi.org/10.1038/s41541-024-00833-z

TY - JOUR

T1 - Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials

AU - Happe, Myra

AU - Hofstetter, Amelia R.

AU - Wang, Jing

AU - Yamshchikov, Galina V.

AU - Holman, La Sonji A.

AU - Novik, Laura

AU - Strom, Larisa

AU - Kiweewa, Francis

AU - Wakabi, Salim

AU - Millard, Monica

AU - Kelley, Colleen F.

AU - Kabbani, Sarah

AU - Edupuganti, Srilatha

AU - Beck, Allison

AU - Kaltovich, Florence

AU - Murray, Tamar

AU - Tsukerman, Susanna

AU - Carr, Derick

AU - Ashman, Carl

AU - Stanley, Daphne A.

AU - Ploquin, Aurélie

AU - Bailer, Robert T.

AU - Schwartz, Richard

AU - Cham, Fatim

AU - Tindikahwa, Allan

AU - Hu, Zonghui

AU - Gordon, Ingelise J.

AU - Rouphael, Nadine

AU - Houser, Katherine V.

AU - Coates, Emily E.

AU - Graham, Barney S.

AU - Koup, Richard A.

AU - Mascola, John R.

AU - Sullivan, Nancy J.

AU - Robb, Merlin L.

AU - Ake, Julie A.

AU - Lyke, Kirsten E.

AU - Mulligan, Mark J.

AU - Ledgerwood, Julie E.

AU - Kibuuka, Hannah

AU - Casazza, Joseph P.

AU - Chen, Grace L.

AU - Enama, Mary E.

AU - Gaudinski, Martin R.

AU - Hendel, Cynthia Starr

AU - Costner, Pamela J.M.

AU - Larkin, Brenda

AU - Mendoza, Floreliz

AU - Sanders, Jamie

AU - Whalen, William R.

AU - Zephir, Kathryn L.

AU - Straling, Judith

AU - DeCederfelt, Hope

AU - Conan-Cibotti, Michelle

AU - Stein, Judy

AU - Pittman, Iris R.

AU - Vasilenko, Olga

AU - DeZure, Adam

AU - Sitar, Sandra

AU - Dropulic, Lesia K.

AU - Plummer, Sarah H.

AU - Nguyen, Thuy A.

AU - Berkowitz, Nina M.

AU - Greenberg, Nancy

AU - Chrisley, Lisa

AU - Billington, Melissa

AU - Wang, Xiaolin

AU - Becker, Jo Anna

AU - Campbell, James D.

AU - Chen, Wilbur H.

AU - Kwon, Alyson

AU - Dorsey, Brenda

AU - Courneya, Jennifer

AU - Komninou, Panagiota

AU - Lee, Myounghee

AU - Bower, Mary

AU - Bailey, Charles A.

AU - Nesheim, Wendy

AU - Girmay, Tigisty

AU - Xu, Jianguo

AU - Ogilvie, Melinda

AU - Sadowski, Joann

AU - Osinski, Eileen

AU - Lai, Lilin

AU - Grimes, Vicki

AU - Kamya, Moses R.

AU - Michael, Nelson L.

AU - Kajumba, Francis

AU - Ananworanich, Jinantat

AU - Mwesigwa, Betty

AU - Kimbugne, Geofrey

AU - Luzinda, Kenneth

AU - Nakabuye, Immaculate

AU - Mukyala, Maureen G.

AU - Kabahubya, Mable

AU - Nakibuuka, Lydia

AU - Matovu, Robinah

PY - 2024/12

Y1 - 2024/12

N2 - Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

AB - Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.

UR - http://www.scopus.com/inward/record.url?scp=85188954079&partnerID=8YFLogxK

U2 - 10.1038/s41541-024-00833-z

DO - 10.1038/s41541-024-00833-z

M3 - Article

AN - SCOPUS:85188954079

SN - 2059-0105

VL - 9

JO - npj Vaccines

JF - npj Vaccines

IS - 1

M1 - 67

ER -

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials

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