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-11918639-B2
Publication Date
2024-03-05
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 provides compositions, vaccines, and methods for inducing protective immunity against filovirus infection, particularly targeting one or more subtypes of Ebola viruses and Marburg virus. The core innovation lies in the use of heterologous prime-boost vaccine regimens combining adenovirus vectors encoding filovirus antigenic proteins with modified vaccinia Ankara (MVA) vectors encoding antigenic proteins from multiple filovirus subtypes.
The problem addressed is the lack of approved vaccines or therapeutics for Ebola Hemorrhagic Fever (EHF) caused by highly lethal filoviruses such as Ebola and Marburg viruses. These viruses cause severe disease with high fatality rates, and current interventions are limited to supportive care. Existing vaccines have had variable results, partly due to the complexity of immune response requirements and the diversity of filovirus species circulating in natural reservoirs. There is a need for improved vaccines capable of generating protective immunity across multiple filovirus subtypes.
The invention demonstrates that prime-boost combinations of replication-incompetent adenovirus vectors, specifically rare serotypes Ad26 or Ad35, together with MVA vectors encoding multiple filovirus antigenic proteins, generate effective immune protection against filovirus infection. The vaccine regimens employ compositions comprising adenovirus vectors encoding antigenic proteins from one or more filovirus subtypes and MVA vectors encoding antigenic proteins from at least two, preferably four, filovirus subtypes.
Claims Coverage
The patent claims cover a combination vaccine comprising specific adenovirus and MVA vectors encoding filovirus antigenic proteins with detailed compositions, dosages, and uses for protective immunity.
Combination vaccine comprising adenovirus and MVA vectors encoding specific filovirus antigens
The vaccine combination comprises (i) an immunologically effective amount of an adenovirus vector encoding an antigenic protein having SEQ ID NO:1 together with a pharmaceutically acceptable carrier, and (ii) an MVA vector comprising nucleic acids 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, together with a pharmaceutically acceptable carrier.
Inclusion of multiple adenovirus vectors encoding antigens from different filovirus subtypes
The first composition can further include adenovirus vectors encoding antigenic proteins of a second and third filovirus subtype, specifically with sequences SEQ ID NO:2 and SEQ ID NO:3.
Use of rare adenovirus serotypes for vectors
The adenovirus vectors used in the combination vaccine are replication-defective vectors of serotypes rAd26 or rAd35.
Specified administration dosage ranges for vectors
The adenovirus vector is administered in amounts ranging from 10^9 to about 10^12 viral particles to a human subject, and the MVA vector is administered in amounts from 1×10^7 to 1×10^9 TCID50.
Use for generating protective immunity against Ebola virus
The vaccine combination is claimed for use in generating a protective immune response against Ebola virus infection and for preparation of pharmaceutical compositions or medicaments.
The claims collectively disclose a heterologous prime-boost vaccine strategy using adenovirus vectors encoding one or more filovirus antigenic proteins and MVA vectors encoding multiple filovirus antigens, specifying vector types, antigen sequences, dosages, and the use for protective immunity against filovirus infections.
Stated Advantages
The vaccine regimens induce strong humoral and cellular immune responses resulting in protective immunity against multiple filovirus subtypes.
The use of rare adenovirus serotypes rAd26 and rAd35 circumvents pre-existing immunity limitations associated with common adenovirus vectors.
Heterologous prime-boost regimens combining adenovirus and MVA vectors enhance immune responses and provide broad protection across filovirus subtypes.
MVA vectors used are replication incompetent, ensuring safety while eliciting potent immune responses.
The compositions demonstrate 100% protection in non-human primate studies against lethal Ebola virus challenge.
Documented Applications
Vaccination of humans and non-human primates to induce protective immunity against multiple filovirus infections including Ebola virus subtypes Zaire, Sudan, Reston, Bundibugyo, Taï Forest and Marburg virus.
Use in medical countermeasures development for bioterrorism or natural outbreaks of Ebola hemorrhagic fever.
Prophylactic vaccination regimens employing heterologous prime-boost strategies combining adenovirus and MVA vectors for filovirus infections.
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