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A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates
- Source :
- PLoS ONE, 13(2):e0192312. Public Library of Science, PLoS ONE, PLoS ONE, Vol 13, Iss 2, p e0192312 (2018)
- Publication Year :
- 2018
-
Abstract
- The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Tai Forest virus (TAFV) and Marburg virus (MARV). Immune responses against filovirus GP have been associated with protection from disease. The GP antigens were expressed by adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified Vaccinia virus Ankara (MVA) vectors, all selected for their strong immunogenicity and good safety profile. Using fully lethal NHP intramuscular challenge models, we assessed different vaccination regimens for immunogenicity and protection from filovirus disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens could give full protection against MARV (range 75%-100% protection) and EBOV (range 50% to 100%) challenge, and partial protection (75%) against SUDV challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full protection against EBOV challenge in a small cohort study. The use of such multivalent vaccines did not show overt immune interference in comparison with monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses and cellular IFNγ responses to each GP expressed by the vaccine, and cross-reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP-specific immune responses (p = 0.0004) were associated with survival from EBOV challenge and less so for cellular immune responses (p = 0.0320). These results demonstrate that it is feasible to generate a multivalent filovirus vaccine that can protect against lethal infection by multiple members of the filovirus family.
- Subjects :
- 0301 basic medicine
Male
Physiology
Humoral Immune Response
lcsh:Medicine
Antibody Response
medicine.disease_cause
Biochemistry
chemistry.chemical_compound
Immune Physiology
Medicine and Health Sciences
Public and Occupational Health
Marburg Virus Disease
Enzyme-Linked Immunoassays
lcsh:Science
Immune Response
Vaccines
Multidisciplinary
Immune System Proteins
biology
Viral Vaccine
Immunogenicity
Ebolavirus
Vaccination and Immunization
Vaccination
Infectious Diseases
Female
Research Article
Infectious Disease Control
Immunology
Research and Analysis Methods
Virus
Antibodies
03 medical and health sciences
medicine
Animals
Antigens
Immunoassays
Ebola virus
lcsh:R
Immunity
Biology and Life Sciences
Proteins
Correction
Viral Vaccines
Hemorrhagic Fever, Ebola
Marburgvirus
biology.organism_classification
Virology
Macaca fascicularis
030104 developmental biology
chemistry
Humoral Immunity
Immunologic Techniques
lcsh:Q
Preventive Medicine
Vaccinia
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, 13(2):e0192312. Public Library of Science, PLoS ONE, PLoS ONE, Vol 13, Iss 2, p e0192312 (2018)
- Accession number :
- edsair.doi.dedup.....ad8b22be7c90f6a7cef8e70f5738c18b