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-11173201-B2
Publication Date
2021-11-16
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, focusing particularly on protection against multiple subtypes of Ebola viruses and Marburg virus. The core innovation lies in the discovery that certain prime-boost vaccination regimens using replication-incompetent adenovirus vectors and Modified Vaccinia Ankara (MVA) viral vectors can induce effective and protective immune responses against filoviruses.
The invention addresses the problem of no currently approved therapeutic or vaccine for Ebola Hemorrhagic Fever (EHF), a severe and often fatal disease caused by filoviruses. Existing vaccine attempts have had variable success due to poorly understood requirements for protective immune responses and the genetic diversity among filovirus subtypes. The invention aims to provide a medical countermeasure, specifically a PAN—filovirus vaccine, which protects against multiple pathogenic filoviruses.
The solution involves heterologous prime-boost vaccination regimes combining adenovirus vectors encoding antigenic proteins from a first filovirus subtype, and MVA vectors encoding antigenic proteins from at least two filovirus subtypes. Various embodiments include compositions where the adenovirus vector encodes glycoproteins with specific amino acid sequences (SEQ ID NO:1 to SEQ ID NO:5), and where there is administration of these vectors in regimes with intervals typically between 1 to 12 weeks. Such approaches generate strong humoral and cellular immune responses, including cross-subtype protection demonstrated in non-human primate studies and human clinical trials.
Claims Coverage
The patent contains multiple independent claims directed to methods and compositions for inducing protective immunity against filovirus infection using combinations of adenovirus and MVA vectors.
Combination of adenovirus and MVA vectors encoding filovirus antigenic proteins
A method of inducing protective immunity by administering a first composition comprising an adenovirus vector encoding an antigenic glycoprotein of a first filovirus subtype (SEQ ID NO:1), and a second composition comprising an MVA vector encoding antigenic glycoproteins of at least two filovirus subtypes.
Use of multiple adenovirus vectors encoding antigenic proteins from different filovirus subtypes
The first composition may further comprise adenovirus vectors encoding antigenic proteins from second and third filovirus subtypes (SEQ ID NO:2 and SEQ ID NO:3), enabling induction of broader protective immunity.
MVA vector encoding antigenic proteins from multiple filovirus subtypes
The MVA vector in the second composition comprises nucleic acids encoding antigenic proteins from at least four filovirus subtypes, specifically those with sequences of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:5.
Use of specific adenovirus vector serotypes to circumvent pre-existing immunity
Use of replication-defective adenovirus vectors rAd26 or rAd35 in vaccination methods for effective immune response generation, overcoming limitations of pre-existing immunity to Ad5 vectors.
The claims cover heterologous prime-boost vaccination methods and immunogenic compositions combining adenovirus vectors encoding specific filovirus glycoproteins, optionally from multiple subtypes, with MVA vectors encoding multiple filovirus antigenic proteins, using specific adenovirus serotypes to optimize immunogenicity and breadth of protection.
Stated Advantages
The vaccination regimens induce strong humoral and cellular immune responses providing 100% protection against highly pathogenic Ebola virus challenge in non-human primates.
Adenovirus vectors of rare serotypes (rAd26 and rAd35) circumvent pre-existing immunity seen with common serotypes, allowing effective vaccination in humans.
MVA vectors have a favorable safety profile, are capable of delivering multiple antigens, and induce both humoral and cellular immunity, supporting broad protective efficacy.
Short prime-boost intervals (as short as 14 days) with an MVA prime and adenovirus boost elicit robust immune responses, allowing flexible and rapid vaccination schedules.
Documented Applications
Vaccination against natural infections of filoviruses, particularly Ebola and Marburg viruses, to prevent Ebola Hemorrhagic Fever (EHF) in humans and non-human primates.
Use as a medical countermeasure to protect against filovirus outbreaks and potential bioterrorism threats involving filoviruses.
Vaccine regimens for post-exposure prophylaxis and pre-exposure immunization against multiple subtypes of pathogenic filoviruses.
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