Methods and compositions for inducing protective immunity against filovirus infection
Inventors
VOLKMANN, Ariane • Steigerwald, Robin • Dirmeier, Ulrike • Pau, Maria Grazia • CALLENDRET, Benoit Christophe Stephan • WARD, Lucy A.
Assignees
Bavarian Nordic AS • Janssen Vaccines and Prevention BV • US Department of Health and Human Services
Publication Number
US-10561721-B2
Publication Date
2020-02-18
Expiration Date
2035-09-03
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Abstract
The present invention provides compositions, vaccines and methods for inducing protective immunity against filovirus infection, particularly protective immunity against infection of one or more subtypes of Ebola viruses and Marburg virus.
Core Innovation
The invention relates to compositions, vaccines, and methods for inducing protective immunity against filovirus infection, specifically targeting one or more subtypes of Ebolaviruses and Marburg virus. The invention emphasizes prime-boost vaccination strategies employing replication incompetent adenovirus vectors and Modified Vaccinia Ankara (MVA) vectors that comprise nucleic acids encoding antigenic proteins from various filovirus subtypes.
The problem addressed by the invention is that filoviruses, including different subtypes of Ebola and Marburg viruses, cause extremely lethal hemorrhagic fever with high mortality rates and no approved therapeutics or vaccines for prevention or treatment. Prior vaccine candidates have had variable results due to limited understanding of protective immune mechanisms and the genetic diversity among filovirus subtypes. There is a need for improved vaccines capable of eliciting broad and protective immunity against multiple filovirus species, especially using safe, immunogenic, and manufacturable vector platforms.
The invention discovers that heterologous prime-boost combinations, particularly involving adenovirus vectors derived from rare serotypes Ad26 or Ad35 and MVA vectors such as the highly attenuated MVA-BN strain expressing multiple filovirus antigens, generate effective immune protection against filovirus infections. The methods include immunizing subjects with an adenovirus vector encoding one or more antigenic filovirus proteins followed by administering an MVA vector encoding antigenic proteins from multiple filovirus subtypes, or vice versa. The compositions include multivalent vaccines targeting several filovirus subtypes with antigenic proteins such as glycoproteins and nucleoproteins, preferably those set forth in SEQ ID NOs:1-5. These prime-boost regimens are demonstrated to induce strong humoral and cellular immune responses, resulting in protective immunity against filovirus challenge.
Claims Coverage
The patent claims cover a total of twelve related features focusing on a combination vaccine, kits, and their components that utilize adenovirus and MVA vectors encoding antigenic proteins from multiple filovirus subtypes. Two independent claims broadly define a vaccine combination and a kit comprising these compositions.
Combination vaccine comprising adenovirus and MVA vectors encoding filovirus antigenic proteins
A vaccine combination comprising (i) a first composition of an adenovirus vector encoding an antigenic protein with SEQ ID NO:1, and (ii) a second composition of an MVA vector encoding antigenic proteins from four filovirus subtypes with SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:5, each with a pharmaceutically acceptable carrier.
Inclusion of multiple adenovirus vectors encoding different filovirus subtypes
The first composition may further include adenovirus vectors encoding antigenic proteins of a second and a third filovirus subtype, expanding the antigenic breadth of the vaccine.
Specific antigenic proteins in adenovirus compositions
The adenovirus composition may include vectors encoding antigenic proteins with SEQ ID NO:2 and SEQ ID NO:3 in addition to SEQ ID NO:1.
Use of rAd26 or rAd35 vectors as adenovirus vectors
The adenovirus vectors in the vaccine compositions or kits are characterized as replication-defective adenovirus vectors based on serotypes 26 or 35.
Kit comprising the vaccine compositions
A kit containing (a) a first composition with an adenovirus vector encoding an antigenic protein having SEQ ID NO:1 and (b) a second composition with an MVA vector encoding antigenic proteins of four filovirus subtypes (SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:5), with options to further include multiple adenovirus vectors encoding additional filovirus subtypes.
The claims establish the invention of a multivalent filovirus vaccine strategy employing specific adenovirus vectors and MVA vectors encoding selected antigenic proteins from different filovirus subtypes, formulated either as combination vaccines or kits to induce protective immunity. These formulations utilize rAd26 or rAd35 adenovirus vectors and MVA vectors encoding glycoproteins and nucleoproteins as the main inventive features.
Stated Advantages
The vaccine platforms (rAd26, rAd35 and MVA-BN vectors) can be produced at high titers under GMP conditions and have demonstrated safety and immunogenicity in humans.
Heterologous prime-boost combinations elicit strong humoral and cellular immune responses against multiple filovirus subtypes, providing protective immunity against lethal filovirus challenge in non-human primates.
The vaccines enable a multivalent approach that protects against several pathogenic filoviruses with a single regimen, addressing the challenge of diverse circulating filoviruses.
The prime-boost regimens enable flexibility in administration order and intervals (1-12 weeks), facilitating clinical application and optimization for immunogenicity.
Documented Applications
Vaccination of humans or non-human primates to induce protective immune responses against infection by one or more subtypes of filoviruses including Ebola viruses (Zaire, Sudan, Bundibugyo, Taï Forest, Reston) and Marburg virus.
Pre-exposure prophylactic vaccination to prevent Ebola Hemorrhagic Fever caused by filovirus infection.
Use as a pan-filovirus vaccine providing immunity across multiple filovirus species and strains through multivalent immunization.
Potential post-exposure prophylactic use to boost immunity following suspected or confirmed filovirus exposure.
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