Use of oil and water emulsions for increasing B cell responses with modified Vaccinia Ankara virus
Inventors
Cheminay, Cédric • Steigerwald, Robin • VOLKMANN, Ariane
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10653766-B2
Publication Date
2020-05-19
Expiration Date
Abstract
The invention relates to compositions, uses, and methods for inducing an immune response against a vaccinia virus. The addition of an oil and water emulsion to MVA can vastly increase the B cell response and particularly neutralizing antibodies against vaccinia virus and encoded recombinant antigens. Thus, the addition of an oil and water emulsion to MVA can increase the protective immune response. The invention encompasses administering a dose of an MVA in an oil and water emulsion to an animal, especially a human.
Core Innovation
The invention relates to formulating a dose of a recombinant modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from a yellow fever virus antigen and an RSV antigen with an emulsion comprising oil and water, to induce vaccinia neutralizing antibodies in an animal. The composition is defined such that it induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion.
The invention further specifies that recombinant MVA is administered in an emulsion format in which the emulsion comprising oil and water provides an enhancement effect on vaccinia neutralizing antibodies relative to a formulation without the emulsion. The improvement is measured at 26 days after immunization and is explicitly tied to the presence of the emulsion, with dependent claim structures refining the induction profile by requiring higher fold increases at later time points, including 35 days after immunization.
In some compositions, the emulsion does not additionally contain the recombinant protein encoded by the recombinant MVA. The claims therefore define an emulsion-adjuvanted recombinant MVA approach where the enhancement of vaccinia neutralizing antibodies is not achieved by adding the encoded recombinant protein into the emulsion. Representative recombinant MVAs include nucleotide sequence references (SEQ ID NOs 1–6) to define particular recombinant MVA constructs used in the compositions.
Claims Coverage
The independent claims are clm-00001, clm-00019, and clm-00022. Across these claims, the core inventive coverage centers on inducing vaccinia neutralizing antibodies at 26 days after immunization using a recombinant MVA dose in an oil-and-water emulsion, with refinements in fold-change thresholds, time points, emulsion components, and MVA dose/sequence constraints.
Emulsion-enhanced induction of vaccinia neutralizing antibodies at 26 days
A pharmaceutical composition for inducing vaccinia neutralizing antibodies in an animal comprising a dose of at least 2×10^7 TCID50 of a recombinant modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of: an antigen of a yellow fever virus; and an antigen of RSV, in an emulsion comprising oil and water, wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion.
Administering emulsion-formulated recombinant MVA to induce antibody response
A method for inducing an immune response against a modified vaccinia Ankara (MVA) virus in an animal comprising administering to the animal a dose of at least 2×10^7 TCID50 of a modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of: an antigen of a yellow fever virus; and an antigen of RSV in an emulsion comprising oil and water, wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion.
Emulsion not additionally containing the recombinant protein
A pharmaceutical composition for inducing vaccinia neutralizing antibodies in an animal comprising a dose of at least 2×10^7 TCID50 of a recombinant modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of: an antigen of a yellow fever virus; and an antigen of RSV in an emulsion comprising oil and water, wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion, and wherein the emulsion does not additionally contain the recombinant protein encoded by the recombinant MVA.
Across clm-00001, clm-00019, and clm-00022, the claims require recombinant MVA encoding either a yellow fever virus antigen or an RSV antigen formulated in an oil-and-water emulsion to induce vaccinia neutralizing antibodies. The core requirement is an at-least 2-fold increase at 26 days post-immunization versus the same composition without the emulsion, with further refinements in dependent claims for increased fold thresholds at later time points and additional constraints on emulsion composition and MVA dose/sequence.
Stated Advantages
Induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization compared to the same composition in the absence of the emulsion.
In dependent claim formats, induces at least a 5-fold or at least a 10-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization compared to the same composition in the absence of the emulsion.
In some compositions, enhances vaccinia neutralizing antibody induction without additionally containing the recombinant protein encoded by the recombinant MVA in the emulsion.
Documented Applications
Using the emulsion-formulated recombinant MVA compositions to induce vaccinia neutralizing antibodies in an animal.
Administering the emulsion-formulated recombinant MVA to an animal to induce an immune response against a modified vaccinia Ankara (MVA) virus with improved vaccinia neutralizing antibody levels.
Interested in licensing this patent?