Polynucleotides encoding flavivirus and alphavirus multivalent antigenic polypeptides
AssigneeMaxygen, Inc.
InventorsJuha Punnonen, Steven H. Bass, Robert Gerald Whalen, Russell Howard, Willem P. C. Stemmer
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Abstract
This invention is directed to antigen library immunization, which provides methods for obtaining antigens having improved properties for therapeutic and other uses. The methods are useful for obtaining improved antigens that can induce an immune response against pathogens, cancer, and other conditions, as well as antigens that are effective in modulating allergy, inflammatory and autoimmune diseases.
Claims54
A nucleic acid comprising a polynucleotide sequence encoding a recombinant multivalent antigenic polypeptide that comprises multiple non-contiguous subsequences of at least a first antigenic polypeptide of at least a first flavivirus or alphavirus and multiple non-contiguous subsequences of at least a second antigenic polypeptide of at least a second flavivirus or alphavirus, each subsequence being positioned relative to its position in the respective antigenic polypeptide, wherein the recombinant multivalent antigenic polypeptide induces an immune response against the first and second antigenic polypeptides that is greater than the immune response induced by any one of the fist and second antigenic polypeptides against any other of the first and second antigenic polypeptides.
A nucleic acid which encodes a recombinant multivalent antigenic polypeptide comprising multiple non-contiguous subsequences of at least a first antigenic polypeptide of at least a first flavivirus or alphavirus and multiple non-contiguous subsequences of at least a second antigenic polypeptide of at least a second flavivirus or alphavirus, each subsequence being positioned relative to its position in the respective antigenic polypeptide, wherein the recombinant multivalent antigenic polypeptide is prepared by a method comprising:
- (1) recombining at least a first nucleic acid comprising a nucleotide sequence that encodes the first antigenic polypeptide and at least a second nucleic acid comprising a nucleotide sequence that encodes the second antigenic polypeptide, wherein at least the first and second nucleic acids differ from each other in two or more nucleotides, to produce a library of recombinant nucleic acids;
- and
- (2) screening the library of recombinant nucleic acids for at least one recombinant nucleic acid that encodes a recombinant multivalent antigenic polypeptide that induces an immune response against each of the first and second flaviviruses or alphaviruses that is greater than the immune response induced by the first antigenic polypeptide against the second flavivirus or alphavirus and the immune response induced by the second antigenic polypeptide against the first flavivirus or alphavirus.
A nucleic acid that encodes a multivalent antigenic polypeptide comprising multiple non-contiguous subsequences of at least a first antigenic polypeptide of at least a first flavivirus or alphavirus and multiple non-contiguous subsequences of at least a second antigenic polypeptide of at least a second flavivirus or alphavirus, each subsequence being positioned relative to its position in the respective antigenic polypeptide, wherein the multivalent antigenic polypeptide induces production of neutralizing antibodies against at least the first and second antigenic polypeptides.
A nucleic acid that encodes a multivalent antigenic polypeptide comprising multiple non-contiguous subsequences of a fast antigenic polypeptide of a dengue-1 virus, multiple non-contiguous subsequences of a second antigenic polypeptide of a dengue-2 virus, multiple non-contiguous subsequences of a third antigenic polypeptide of a dengue-3 virus, and multiple noncontiguous subsequences of a fourth antigenic polypeptide of a dengue-4 virus, each subsequence being positioned relative to its position in the first, second, third, or fourth antigenic polypeptide, wherein the multivalent antigenic polypeptide induces production of neutralizing antibodies against the dengue-1 virus, dengue-2 virus, dengue-3 virus, and dengue-4 virus.
Dependencies are inferred from the claim text.