TY - JOUR
T1 - Recombinant subunit vaccines protect guinea pigs from lethal Ebola virus challenge
AU - Lehrer, Axel T.
AU - Wong, Teri Ann S.
AU - Lieberman, Michael M.
AU - Johns, Lisa
AU - Medina, Liana
AU - Feldmann, Friederike
AU - Feldmann, Heinz
AU - Marzi, Andrea
N1 - Funding Information:
The authors are grateful to the BSL4 animal care and veterinary staff of the Rocky Mountain Veterinary Branch for their support of this study. The immunogenicity portion of the first study was performed via DMID Preclinical Services (NIH/NIAID). This work was funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health , by a grant from NIH/NIAID ( 1R43AI066616 ), and through corporate funds from PanThera Biopharma, LLC. We also greatly acknowledge the gift of adjuvants CoVaccine HT TM from BTG International (London, UK) and GPI-0100 from Hawaii Biotech, Inc. (Honolulu, USA).
Funding Information:
The authors are grateful to the BSL4 animal care and veterinary staff of the Rocky Mountain Veterinary Branch for their support of this study. The immunogenicity portion of the first study was performed via DMID Preclinical Services (NIH/NIAID). This work was funded in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, by a grant from NIH/NIAID (1R43AI066616), and through corporate funds from PanThera Biopharma, LLC. We also greatly acknowledge the gift of adjuvants CoVaccine HTTM from BTG International (London, UK) and GPI-0100 from Hawaii Biotech, Inc. (Honolulu, USA). All authors contributed substantially to the reported research and approved the manuscript. The authors declare no conflicts of interests.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/11/8
Y1 - 2019/11/8
N2 - Ebola virus (EBOV) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. In humans, the case fatality rates in the outbreaks can reach 90%. During the West African epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. Currently, we are facing an uncontained larger outbreak in the Democratic Republic of the Congo. Even though EBOV was discovered in 1976, extensive efforts to develop countermeasures, particularly therapeutics and vaccines, started late and there is still no FDA-approved product available. Nevertheless, one candidate vaccine, the rVSV-ZEBOV, is being used in clinical trials during the current outbreak with the hope of ending the human transmission chains. However, adverse reactions to administration of some EBOV vaccines have been reported; therefore, we have developed a safe and efficacious formulation of insect-cell derived adjuvanted protein vaccines. Vaccine candidates containing the EBOV glycoprotein with or without matrix proteins VP24 and VP40 formulated with one of three different adjuvants were tested in guinea pigs for immunogenicity and efficacy against lethal EBOV challenge. The results demonstrated that these vaccine candidates engendered high titers of antigen-specific antibodies in immunized animals and two of these vaccine candidates afforded complete or nearly complete protection against lethal challenge. Interestingly, we found a sex bias in partially protected immunized groups with male guinea pigs succumbing to disease and females surviving. In summary, we developed a safe and immunogenic adjuvanted subunit vaccine uniformly protective against EBOV disease in guinea pigs.
AB - Ebola virus (EBOV) is among the deadliest pathogens known to man causing infrequent outbreaks of hemorrhagic disease. In humans, the case fatality rates in the outbreaks can reach 90%. During the West African epidemic almost 30,000 people were infected and of these over 11,000 fatalities were reported. Currently, we are facing an uncontained larger outbreak in the Democratic Republic of the Congo. Even though EBOV was discovered in 1976, extensive efforts to develop countermeasures, particularly therapeutics and vaccines, started late and there is still no FDA-approved product available. Nevertheless, one candidate vaccine, the rVSV-ZEBOV, is being used in clinical trials during the current outbreak with the hope of ending the human transmission chains. However, adverse reactions to administration of some EBOV vaccines have been reported; therefore, we have developed a safe and efficacious formulation of insect-cell derived adjuvanted protein vaccines. Vaccine candidates containing the EBOV glycoprotein with or without matrix proteins VP24 and VP40 formulated with one of three different adjuvants were tested in guinea pigs for immunogenicity and efficacy against lethal EBOV challenge. The results demonstrated that these vaccine candidates engendered high titers of antigen-specific antibodies in immunized animals and two of these vaccine candidates afforded complete or nearly complete protection against lethal challenge. Interestingly, we found a sex bias in partially protected immunized groups with male guinea pigs succumbing to disease and females surviving. In summary, we developed a safe and immunogenic adjuvanted subunit vaccine uniformly protective against EBOV disease in guinea pigs.
KW - Glycoprotein
KW - Recombinant protein
KW - VP24
KW - VP40
KW - Zaire ebolavirus
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U2 - 10.1016/j.vaccine.2019.06.035
DO - 10.1016/j.vaccine.2019.06.035
M3 - Article
C2 - 31324500
AN - SCOPUS:85068836037
VL - 37
SP - 6942
EP - 6950
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 47
ER -