Golden Triangle, NC, United States
Golden Triangle, NC, United States

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Patent
AlphaVax Inc. | Date: 2014-03-28

The present disclosure provides TC-83 VEE-derived replicons, alphaviral replicon particles and immunogenic compositions containing TC-83 alphaviral replicon particles which direct the expression of at least one antigen when introduced into a suitable host cell. The TC-83 VEE-derived ARPs described herein are improved in that they are subject to a lower vector-specific immune response than prior art ARPs.


The immune response to an antigen of interest, especially one in purified form, can be significantly enhanced by the simultaneous administration of an alphavirus replicon particle which expresses the same antigen. This allows for the use of significantly smaller quantities of the protein antigen than in conventional immunization strategies, and this new immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.


Patent
AlphaVax Inc. | Date: 2014-02-05

Provided herein are helper nucleic acids comprising at least one microRNA target sequence of an endogenous, cellular microRNA and a nucleic acid encoding a viral protein, wherein the microRNA target sequence is located in the untranslated or translated region of the nucleic acid encoding the viral protein. Also provided are vector systems, compositions and cells comprising the provided helper nucleic acids and a vector or replicon. Methods of making virus-like replicon particles and populations of virus-like replicon particles (VRP) are also provided.


Patent
AlphaVax Inc. | Date: 2016-08-11

The present disclosure provides TC-83 VEE-derived replicons, alphaviral replicon particles and immunogenic compositions containing TC-83 alphaviral replicon particles which direct the expression of at least one antigen when introduced into a suitable host cell. The TC-83 VEE-derived ARPs described herein are improved in that they are subject to a lower vector-specific immune response than prior art ARPs.


Patent
AlphaVax Inc. | Date: 2010-07-06

The present disclosure provides TC-83 VEE-derived replicons, alphaviral replicon particles and immunogenic compositions containing TC-83 alphaviral replicon particles which direct the expression of at least one antigen when introduced into a suitable host cell. The TC-83 VEE-derived ARPs described herein are improved in that they are subject to a lower vector-specific immune response than prior art ARPs.


Patent
AlphaVax Inc. | Date: 2011-03-02

Provided herein are methods for producing alphavirus replicon particles in high yield; replicon RNAs are electroporated into permissive cells, where the cells are at a relatively high density, together with at least one helper nucleic acid providing the necessary functions for packaging. After a growth period in appropriate medium, alphavirus replicon particles are harvested from the surfaces of the cells in which they were produced using a salt wash in which the salt concentration is from about 0.2 to about 5 M sodium chloride, calcium chloride, magnesium chloride, potassium chloride, ammonium acetate, ammonium bicarbonate, among others. After dilution, if necessary, the particles can be purified by a suitable chromatographic technique.


The immune response to an antigen of interest, especially one in purified form, can be significantly enhanced by the simultaneous administration of an alphavirus replicon particle which expresses the same antigen. This allows for the use of significantly smaller quantities of the protein antigen than in conventional immunization strategies, and this new immunization strategy can also eliminate the need for boosting administration of the antigen or it can reduce the number of boosts required for an effective immune response to the antigen.


The present invention provides use of an isolated RNA molecule comprising: a) an alphavirus 5 replication recognition sequence, wherein at least one initiation codon has been removed from the 5 replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3 replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5 and 3 replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins in inducing an immune response in a subject or for use in immunizing a subject or for treating a subject.


Disclosed are methods for preparing dried (preferably lyophilized) preparations comprising a population of alphaviruses or alphavirus replicon particles, a sugar or polyol, a surfactant and a salt and preparations made by these methods, both in the dried form but also as liquids prior to drying or after reconstituting dried preparations. These preparations may further comprise a plasticizer and/or a bulking agent. These preparations are readily reconstituted, with little or no loss in infectivity of the viruses or replicon particles.


Patent
AlphaVax Inc. | Date: 2015-07-06

The present disclosure provides TC-83 VEE-derived replicons, alphaviral replicon particles and immunogenic compositions containing TC-83 alphaviral replicon particles which direct the expression of at least one antigen when introduced into a suitable host cell. The TC-83 VEE-derived ARPs described herein are improved in that they are subject to a lower vector-specific immune response than prior art ARPs.

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