Antigen library immunization
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.
Claims47
A recombinant multivalent antigenic polypeptide that comprises multiple non-contiguous subsequences of at least a first antigenic polypeptide of a first flavivirus or alphavirus and multiple noncontiguous subsequences of at least a second antigenic polypeptide of a second flavivirus or alphavirus, each subsequence being positioned relative to its position in the first or second antigenic polypeptide,
- wherein the recombinant multivalent antigenic polypeptide induces an immune response against each of the first and second antigenic polypeptides that is greater than the immune response induced by any one of the first and second antigenic polypeptides against any other of the first and second antigenic polypeptides.
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 first or second antigenic polypeptide, wherein the recombinant multivalent antigenic polypeptide is prepared by the 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 optimized recombinant nucleic acid that encodes a recombiant multivalent antigenic polypeptide that induces an imnmune 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 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, multiple non-contiguous subsequences of at least a second antigenic polypeptide of at least a second flavivirus or alphavirus, and multiple non-contiguous subsequences of at least a third antigenic polypeptide of at least a third flavivirus or alphavirus, each subsequence being positioned relative to its position in the first, second, or third antigenic polypeptide,
- wherein the recombinant multivalent antigenic polypeptide induces:
- (i) an immune response against the first flavivirus or alphavirus that is greater than the immune response induced by the second or third antigenic polypeptide against the first flavivirus or alphavirus;
- (ii) an immune response against the second flavivirus or alphavirus that is greater than the immune response induced by the first or third antigenic polypeptide against the second flavivirus or alphavirus;
- and
- (iii) an immune response against the third flavivirus or alphavirus that is greater than the immune response induced by the first or second antigenic polypeptide against the third flavivirus or alphavirus.
A multivalent antigenic polypeptide comprising multiple non-contiguous subsequences of a first 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 non-contiguous 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 an immune response against each of a dengue-1 virus, dengue-2 virus, dengue-3 virus, and dengue-4 virus that is greater than:
- (i) the immune response induced by the first antigenic polypeptide against a dengue-2 virus, dengue-3 virus, or dengue-4 virus;
- (ii) the immune response induced by the second antigenic polypeptide against a dengue-1 virus, dengue-3 virus, or dengue-4 virus;
- (iii) the immune response induced by the third antigenic polypeptide against a dengue-1 virus, dengue-2 virus, or dengue-4 virus;
- and
- (iv) the immune response induced by the fourth antigenic polypeptide against a dengue-1 virus, dengue-2 virus, or dengue-3 virus.
A chimeric dengue virus polypeptide comprising multiple non-contiguous subsequences of an envelope protein of a dengue-1 virus, multiple non-contiguous subsequences of an envelope protein of a dengue-2 virus, multiple non-contiguous subsequences of an envelope protein of a dengue-3 virus, and multiple non-contiguous subsequences of an envelope protein of a dengue-4 virus, each subsequence being positioned relative to its position in the respective envelope protein, wherein the chimeric dengue virus polypeptide induces production of neutralizing antibodies against each of dengue-1 virus, dengue-2 virus, dengue-3 virus, and dengue-4 virus.
A chimeric flavivirus or alphavirus polypeptide comprising multiple non-contiguous subsequences of an envelope protein of at least a first flavivirus or alphavirus, multiple non-contiguous subsequences of an envelope protein of at least a second flavivirus or alphavirus, and multiple non-contiguous subsequences of an envelope protein of at least a third flavivirus or alphavirus, each subsequence being positioned relative to its position in the respective envelope protein, wherein the chimeric flavivirus or alphavirus polypeptide induces production of neutralizing antibodies against each of the first, second, and third flaviviruses or alphaviruses.
A chimeric 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 chimeric antigenic polypeptide includes production of neutralizing antibodies against at least the first and second antigenic polypeptides or first and second flaviviruses or alphaviruses.
Dependencies are inferred from the claim text.