BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge

Valentina Franceschi, Scott Parker, Sarah Jacca, Ryan W. Crump, Konstantin Doronin, Edguardo Hembrador, Daniela Pompilio, Giulia Tebaldi, Ryan Estep, Scott Wong, Mark R. Buller, Gaetano Donofrio

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic inWest Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980,meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies againstMPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4- A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weightloss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-AEF1α- M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100%alone and 80%in combination, STAT1(-/-) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.

Original languageEnglish (US)
Article numbere0003850
JournalPLoS Neglected Tropical Diseases
Volume9
Issue number6
DOIs
StatePublished - Jun 18 2015

Fingerprint

Bovine Herpesvirus 4
Monkeypox virus
Heterophile Antigens
Zoonoses
Virus Diseases
Vaccination
Vaccines
Orthopoxvirus
Neglected Diseases
Cross Protection
Congo
Immunization Programs
Smallpox
Transgenes
Knockout Mice
Population

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge. / Franceschi, Valentina; Parker, Scott; Jacca, Sarah; Crump, Ryan W.; Doronin, Konstantin; Hembrador, Edguardo; Pompilio, Daniela; Tebaldi, Giulia; Estep, Ryan; Wong, Scott; Buller, Mark R.; Donofrio, Gaetano.

In: PLoS Neglected Tropical Diseases, Vol. 9, No. 6, e0003850, 18.06.2015.

Research output: Contribution to journalArticle

Franceschi, V, Parker, S, Jacca, S, Crump, RW, Doronin, K, Hembrador, E, Pompilio, D, Tebaldi, G, Estep, R, Wong, S, Buller, MR & Donofrio, G 2015, 'BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge', PLoS Neglected Tropical Diseases, vol. 9, no. 6, e0003850. https://doi.org/10.1371/journal.pntd.0003850
Franceschi, Valentina ; Parker, Scott ; Jacca, Sarah ; Crump, Ryan W. ; Doronin, Konstantin ; Hembrador, Edguardo ; Pompilio, Daniela ; Tebaldi, Giulia ; Estep, Ryan ; Wong, Scott ; Buller, Mark R. ; Donofrio, Gaetano. / BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge. In: PLoS Neglected Tropical Diseases. 2015 ; Vol. 9, No. 6.
@article{c768405ac61a4b39b685fffc4ebbebca,
title = "BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge",
abstract = "Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic inWest Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980,meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies againstMPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4- A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weightloss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-AEF1α- M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100{\%}alone and 80{\%}in combination, STAT1(-/-) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.",
author = "Valentina Franceschi and Scott Parker and Sarah Jacca and Crump, {Ryan W.} and Konstantin Doronin and Edguardo Hembrador and Daniela Pompilio and Giulia Tebaldi and Ryan Estep and Scott Wong and Buller, {Mark R.} and Gaetano Donofrio",
year = "2015",
month = "6",
day = "18",
doi = "10.1371/journal.pntd.0003850",
language = "English (US)",
volume = "9",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - BoHV-4-based vector single heterologous antigen delivery protects STAT1(-/-) mice from monkeypoxvirus lethal challenge

AU - Franceschi, Valentina

AU - Parker, Scott

AU - Jacca, Sarah

AU - Crump, Ryan W.

AU - Doronin, Konstantin

AU - Hembrador, Edguardo

AU - Pompilio, Daniela

AU - Tebaldi, Giulia

AU - Estep, Ryan

AU - Wong, Scott

AU - Buller, Mark R.

AU - Donofrio, Gaetano

PY - 2015/6/18

Y1 - 2015/6/18

N2 - Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic inWest Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980,meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies againstMPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4- A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weightloss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-AEF1α- M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100%alone and 80%in combination, STAT1(-/-) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.

AB - Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic inWest Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Smallpox vaccination provides good cross-protection against MPX; however, the vaccination campaign ended in Africa in 1980,meaning that a large proportion of the population is currently unprotected against MPXV infection. Disease control hinges on deterring zoonotic exposure to the virus and, barring that, interrupting person-to-person spread. However, there are no FDA-approved therapies againstMPX, and current vaccines are limited due to safety concerns. For this reason, new studies on pathogenesis, prophylaxis and therapeutics are still of great interest, not only for the scientific community but also for the governments concerned that MPXV could be used as a bioterror agent. In the present study, a new vaccination strategy approach based on three recombinant bovine herpesvirus 4 (BoHV-4) vectors, each expressing different MPXV glycoproteins, A29L, M1R and B6R were investigated in terms of protection from a lethal MPXV challenge in STAT1 knockout mice. BoHV-4-A-CMV-A29LgD106ΔTK, BoHV-4- A-EF1α-M1RgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK were successfully constructed by recombineering, and their capacity to express their transgene was demonstrated. A small challenge study was performed, and all three recombinant BoHV-4 appeared safe (no weightloss or obvious adverse events) following intraperitoneal administration. Further, BoHV-4-AEF1α- M1RgD106ΔTK alone or in combination with BoHV-4-A-CMV-A29LgD106ΔTK and BoHV-4-A-EF1α-B6RgD106ΔTK, was shown to be able to protect, 100%alone and 80%in combination, STAT1(-/-) mice against mortality and morbidity. This work demonstrated the efficacy of BoHV-4 based vectors and the use of BoHV-4 as a vaccine-vector platform.

UR - http://www.scopus.com/inward/record.url?scp=84934783688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934783688&partnerID=8YFLogxK

U2 - 10.1371/journal.pntd.0003850

DO - 10.1371/journal.pntd.0003850

M3 - Article

C2 - 26086739

AN - SCOPUS:84934783688

VL - 9

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

IS - 6

M1 - e0003850

ER -