Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

Natalie I. Mazur; Jonne Terstappen; Ranju Baral; Azucena Bardají; Philippe Beutels; Ursula J. Buchholz; Cheryl Cohen; James E. Crowe; Clare L. Cutland; Linda Eckert; Daniel Feikin; Tiffany Fitzpatrick; Youyi Fong; Barney S. Graham; Terho Heikkinen; Deborah Higgins; Siddhivinayak Hirve; Keith P. Klugman; Leyla Kragten-Tabatabaie; Philippe Lemey; Romina Libster; Yvette Löwensteyn; Asuncion Mejias; Flor M. Munoz; Patrick K. Munywoki; Lawrence Mwananyanda; Harish Nair; Marta C. Nunes; Octavio Ramilo; Peter Richmond; Tracy J. Ruckwardt; Charles Sande; Padmini Srikantiah; Naveen Thacker; Kody A. Waldstein; Dan Weinberger; Joanne Wildenbeest; Dexter Wiseman; Heather J. Zar; Maria Zambon; Louis Bont

doi:10.1016/S1473-3099(22)00291-2

Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

Natalie I. Mazur, Jonne Terstappen, Ranju Baral, Azucena Bardají, Philippe Beutels, Ursula J. Buchholz, Cheryl Cohen, James E. Crowe, Clare L. Cutland, Linda Eckert, Daniel Feikin, Tiffany Fitzpatrick, Youyi Fong, Barney S. Graham, Terho Heikkinen, Deborah Higgins, Siddhivinayak Hirve, Keith P. Klugman, Leyla Kragten-Tabatabaie, Philippe LemeyRomina Libster, Yvette Löwensteyn, Asuncion Mejias, Flor M. Munoz, Patrick K. Munywoki, Lawrence Mwananyanda, Harish Nair, Marta C. Nunes, Octavio Ramilo, Peter Richmond, Tracy J. Ruckwardt, Charles Sande, Padmini Srikantiah, Naveen Thacker, Kody A. Waldstein, Dan Weinberger, Joanne Wildenbeest, Dexter Wiseman, Heather J. Zar, Maria Zambon, Louis Bont^*

^*Corresponding author for this work

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Abstract

Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.

Original language	English
Pages (from-to)	e2-e21
Journal	The Lancet Infectious Diseases
Volume	23
Issue number	1
Early online date	8 Aug 2022
DOIs	https://doi.org/10.1016/S1473-3099(22)00291-2
Publication status	Published - Jan 2023

Bibliographical note

Funding Information: UMCU received minor funding from The Bill & Melinda Gates Medical Research Institute. DMW has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax, unrelated to this manuscript; and is a principal investigator with grant support from Pfizer and Merck to Yale University, unrelated to this manuscript. NIM has regular interaction with pharameutical and other industrial partners: UMC Utrecht has received fees for invited lectures by Abbvie, Merck, and Sanofi. LB has regular interaction with pharmaceutical and other industrial partners. BSG is an inventor of patents for RSV vaccines using the stabilised prefusion F protein. AM has received research grants from National Institutes of Health, Janssen, and Merck institution; fees for participation in advisory boards from Janssen, Sanofi-Pasteur, and Merck; and fees for educational lectures from Sanofi-Pasteur and AstraZeneca. TJR was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. BSG was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UJB was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UMCU has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, Janssen, Pfizer, the Bill & Melinda Gates Foundation, and MeMed Diagnostics. UMCU has received major cash or in-kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015-17 (total annual estimate less than €20 000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, and Janssen (total annual estimate less than €20 000). Dr. Bont is the founding chairman of the ReSViNET Foundation.

Open Access: Free to read, but no Open Access licence.

Publisher Copyright: © 2022 Elsevier Ltd. All rights reserved

Citation: Natalie I Mazur, Jonne Terstappen, Ranju Baral, Azucena Bardají, Philippe Beutels, Ursula J Buchholz, Cheryl Cohen, James E Crowe, Clare L Cutland, Linda Eckert, Daniel Feikin, Tiffany Fitzpatrick, Youyi Fong, Barney S Graham, Terho Heikkinen, Deborah Higgins, Siddhivinayak Hirve, Keith P Klugman, Leyla Kragten-Tabatabaie, Philippe Lemey, Romina Libster, Yvette Löwensteyn, Asuncion Mejias, Flor M Munoz, Patrick K Munywoki, Lawrence Mwananyanda, Harish Nair, Marta C Nunes, Octavio Ramilo, Peter Richmond, Tracy J Ruckwardt, Charles Sande, Padmini Srikantiah, Naveen Thacker, Kody A Waldstein, Dan Weinberger, Joanne Wildenbeest, Dexter Wiseman, Heather J Zar, Maria Zambon, Louis Bont,
Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape, The Lancet Infectious Diseases, Volume 23, Issue 1, 2023,
Pages e2-e21, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(22)00291-2.

DOI: https://doi.org/10.1016/S1473-3099(22)00291-2

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10.1016/S1473-3099(22)00291-2

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Mazur, N. I., Terstappen, J., Baral, R., Bardají, A., Beutels, P., Buchholz, U. J., Cohen, C., Crowe, J. E., Cutland, C. L., Eckert, L., Feikin, D., Fitzpatrick, T., Fong, Y., Graham, B. S., Heikkinen, T., Higgins, D., Hirve, S., Klugman, K. P., Kragten-Tabatabaie, L., ... Bont, L. (2023). Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape. The Lancet Infectious Diseases, 23(1), e2-e21. https://doi.org/10.1016/S1473-3099(22)00291-2

@article{3a81acc9ae4648e3899a2e821f256352,

title = "Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape",

abstract = "Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.",

author = "Mazur, {Natalie I.} and Jonne Terstappen and Ranju Baral and Azucena Bardaj{\'i} and Philippe Beutels and Buchholz, {Ursula J.} and Cheryl Cohen and Crowe, {James E.} and Cutland, {Clare L.} and Linda Eckert and Daniel Feikin and Tiffany Fitzpatrick and Youyi Fong and Graham, {Barney S.} and Terho Heikkinen and Deborah Higgins and Siddhivinayak Hirve and Klugman, {Keith P.} and Leyla Kragten-Tabatabaie and Philippe Lemey and Romina Libster and Yvette L{\"o}wensteyn and Asuncion Mejias and Munoz, {Flor M.} and Munywoki, {Patrick K.} and Lawrence Mwananyanda and Harish Nair and Nunes, {Marta C.} and Octavio Ramilo and Peter Richmond and Ruckwardt, {Tracy J.} and Charles Sande and Padmini Srikantiah and Naveen Thacker and Waldstein, {Kody A.} and Dan Weinberger and Joanne Wildenbeest and Dexter Wiseman and Zar, {Heather J.} and Maria Zambon and Louis Bont",

note = "Funding Information: UMCU received minor funding from The Bill & Melinda Gates Medical Research Institute. DMW has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax, unrelated to this manuscript; and is a principal investigator with grant support from Pfizer and Merck to Yale University, unrelated to this manuscript. NIM has regular interaction with pharameutical and other industrial partners: UMC Utrecht has received fees for invited lectures by Abbvie, Merck, and Sanofi. LB has regular interaction with pharmaceutical and other industrial partners. BSG is an inventor of patents for RSV vaccines using the stabilised prefusion F protein. AM has received research grants from National Institutes of Health, Janssen, and Merck institution; fees for participation in advisory boards from Janssen, Sanofi-Pasteur, and Merck; and fees for educational lectures from Sanofi-Pasteur and AstraZeneca. TJR was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. BSG was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UJB was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UMCU has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, Janssen, Pfizer, the Bill & Melinda Gates Foundation, and MeMed Diagnostics. UMCU has received major cash or in-kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015-17 (total annual estimate less than €20 000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, and Janssen (total annual estimate less than €20 000). Dr. Bont is the founding chairman of the ReSViNET Foundation. Open Access: Free to read, but no Open Access licence. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd. All rights reserved Citation: Natalie I Mazur, Jonne Terstappen, Ranju Baral, Azucena Bardaj{\'i}, Philippe Beutels, Ursula J Buchholz, Cheryl Cohen, James E Crowe, Clare L Cutland, Linda Eckert, Daniel Feikin, Tiffany Fitzpatrick, Youyi Fong, Barney S Graham, Terho Heikkinen, Deborah Higgins, Siddhivinayak Hirve, Keith P Klugman, Leyla Kragten-Tabatabaie, Philippe Lemey, Romina Libster, Yvette L{\"o}wensteyn, Asuncion Mejias, Flor M Munoz, Patrick K Munywoki, Lawrence Mwananyanda, Harish Nair, Marta C Nunes, Octavio Ramilo, Peter Richmond, Tracy J Ruckwardt, Charles Sande, Padmini Srikantiah, Naveen Thacker, Kody A Waldstein, Dan Weinberger, Joanne Wildenbeest, Dexter Wiseman, Heather J Zar, Maria Zambon, Louis Bont, Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape, The Lancet Infectious Diseases, Volume 23, Issue 1, 2023, Pages e2-e21, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(22)00291-2. DOI: https://doi.org/10.1016/S1473-3099(22)00291-2",

year = "2023",

month = jan,

doi = "10.1016/S1473-3099(22)00291-2",

language = "English",

volume = "23",

pages = "e2--e21",

journal = "The Lancet Infectious Diseases",

issn = "1473-3099",

publisher = "Elsevier Ltd.",

number = "1",

}

Mazur, NI, Terstappen, J, Baral, R, Bardají, A, Beutels, P, Buchholz, UJ, Cohen, C, Crowe, JE, Cutland, CL, Eckert, L, Feikin, D, Fitzpatrick, T, Fong, Y, Graham, BS, Heikkinen, T, Higgins, D, Hirve, S, Klugman, KP, Kragten-Tabatabaie, L, Lemey, P, Libster, R, Löwensteyn, Y, Mejias, A, Munoz, FM, Munywoki, PK, Mwananyanda, L, Nair, H, Nunes, MC, Ramilo, O, Richmond, P, Ruckwardt, TJ, Sande, C, Srikantiah, P, Thacker, N, Waldstein, KA, Weinberger, D, Wildenbeest, J, Wiseman, D, Zar, HJ, Zambon, M & Bont, L 2023, 'Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape', The Lancet Infectious Diseases, vol. 23, no. 1, pp. e2-e21. https://doi.org/10.1016/S1473-3099(22)00291-2

TY - JOUR

T1 - Respiratory syncytial virus prevention within reach

T2 - the vaccine and monoclonal antibody landscape

AU - Mazur, Natalie I.

AU - Terstappen, Jonne

AU - Baral, Ranju

AU - Bardají, Azucena

AU - Beutels, Philippe

AU - Buchholz, Ursula J.

AU - Cohen, Cheryl

AU - Crowe, James E.

AU - Cutland, Clare L.

AU - Eckert, Linda

AU - Feikin, Daniel

AU - Fitzpatrick, Tiffany

AU - Fong, Youyi

AU - Graham, Barney S.

AU - Heikkinen, Terho

AU - Higgins, Deborah

AU - Hirve, Siddhivinayak

AU - Klugman, Keith P.

AU - Kragten-Tabatabaie, Leyla

AU - Lemey, Philippe

AU - Libster, Romina

AU - Löwensteyn, Yvette

AU - Mejias, Asuncion

AU - Munoz, Flor M.

AU - Munywoki, Patrick K.

AU - Mwananyanda, Lawrence

AU - Nair, Harish

AU - Nunes, Marta C.

AU - Ramilo, Octavio

AU - Richmond, Peter

AU - Ruckwardt, Tracy J.

AU - Sande, Charles

AU - Srikantiah, Padmini

AU - Thacker, Naveen

AU - Waldstein, Kody A.

AU - Weinberger, Dan

AU - Wildenbeest, Joanne

AU - Wiseman, Dexter

AU - Zar, Heather J.

AU - Zambon, Maria

AU - Bont, Louis

N1 - Funding Information: UMCU received minor funding from The Bill & Melinda Gates Medical Research Institute. DMW has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax, unrelated to this manuscript; and is a principal investigator with grant support from Pfizer and Merck to Yale University, unrelated to this manuscript. NIM has regular interaction with pharameutical and other industrial partners: UMC Utrecht has received fees for invited lectures by Abbvie, Merck, and Sanofi. LB has regular interaction with pharmaceutical and other industrial partners. BSG is an inventor of patents for RSV vaccines using the stabilised prefusion F protein. AM has received research grants from National Institutes of Health, Janssen, and Merck institution; fees for participation in advisory boards from Janssen, Sanofi-Pasteur, and Merck; and fees for educational lectures from Sanofi-Pasteur and AstraZeneca. TJR was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. BSG was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UJB was financially supported by the Intramural Program of the National Institute of Allergy & Infectious Diseases, National Institute of Health. UMCU has received major funding (>€100 000 per industrial partner) for investigator-initiated studies from AbbVie, MedImmune, Janssen, Pfizer, the Bill & Melinda Gates Foundation, and MeMed Diagnostics. UMCU has received major cash or in-kind funding as part of the public private partnership IMI-funded RESCEU project from GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi. UMCU has received major funding by Julius Clinical for participating in the INFORM study sponsored by MedImmune. UMCU has received minor funding for participation in trials by Regeneron and Janssen from 2015-17 (total annual estimate less than €20 000). UMCU received minor funding for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, Novavax, Pfizer, and Janssen (total annual estimate less than €20 000). Dr. Bont is the founding chairman of the ReSViNET Foundation. Open Access: Free to read, but no Open Access licence. Publisher Copyright: © 2022 Elsevier Ltd. All rights reserved Citation: Natalie I Mazur, Jonne Terstappen, Ranju Baral, Azucena Bardají, Philippe Beutels, Ursula J Buchholz, Cheryl Cohen, James E Crowe, Clare L Cutland, Linda Eckert, Daniel Feikin, Tiffany Fitzpatrick, Youyi Fong, Barney S Graham, Terho Heikkinen, Deborah Higgins, Siddhivinayak Hirve, Keith P Klugman, Leyla Kragten-Tabatabaie, Philippe Lemey, Romina Libster, Yvette Löwensteyn, Asuncion Mejias, Flor M Munoz, Patrick K Munywoki, Lawrence Mwananyanda, Harish Nair, Marta C Nunes, Octavio Ramilo, Peter Richmond, Tracy J Ruckwardt, Charles Sande, Padmini Srikantiah, Naveen Thacker, Kody A Waldstein, Dan Weinberger, Joanne Wildenbeest, Dexter Wiseman, Heather J Zar, Maria Zambon, Louis Bont, Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape, The Lancet Infectious Diseases, Volume 23, Issue 1, 2023, Pages e2-e21, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(22)00291-2. DOI: https://doi.org/10.1016/S1473-3099(22)00291-2

PY - 2023/1

Y1 - 2023/1

N2 - Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.

AB - Respiratory syncytial virus is the second most common cause of infant mortality and a major cause of morbidity and mortality in older adults (aged >60 years). Efforts to develop a respiratory syncytial virus vaccine or immunoprophylaxis remain highly active. 33 respiratory syncytial virus prevention candidates are in clinical development using six different approaches: recombinant vector, subunit, particle-based, live attenuated, chimeric, and nucleic acid vaccines; and monoclonal antibodies. Nine candidates are in phase 3 clinical trials. Understanding the epitopes targeted by highly neutralising antibodies has resulted in a shift from empirical to rational and structure-based vaccine and monoclonal antibody design. An extended half-life monoclonal antibody for all infants is likely to be within 1 year of regulatory approval (from August, 2022) for high-income countries. Live-attenuated vaccines are in development for older infants (aged >6 months). Subunit vaccines are in late-stage trials for pregnant women to protect infants, whereas vector, subunit, and nucleic acid approaches are being developed for older adults. Urgent next steps include ensuring access and affordability of a respiratory syncytial virus vaccine globally. This review gives an overview of respiratory syncytial virus vaccines and monoclonal antibodies in clinical development highlighting different target populations, antigens, and trial results.

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U2 - 10.1016/S1473-3099(22)00291-2

DO - 10.1016/S1473-3099(22)00291-2

M3 - Review article

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AN - SCOPUS:85136720386

SN - 1473-3099

VL - 23

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JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

IS - 1

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Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

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