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PubMed2003

Immunogenicity of polymerizable synthetic peptides derived from a vaccine candidate against schistosomiasis: the asparaginyl endopeptidase (Sm32).

The asparaginyl endopeptidase (Sm32) is expressed in the gastrodermal cells of the schistosome gut and in the head glands of the cercariae. Possibly, Sm32 hydrolyzes pro-proteins involved in the degradation of host hemoglobin [Parasitol. Today 12 (1996) 125]. Preliminary evidences using an Sj32/Sm32 murine vaccine have shown a profound effect on oviposition and worm burden [Chin. J. Schist. Control. 7 (1995) 72; Bull. Human Med. Univ. 24 (1999) 225; Vaccine 20 (2002) 439]. The importance of Sm32 as a novel vaccine candidate is based on the possibility of preventing the maturation of other cathepsins and/or preventing schistosome skin invasion. We studied the immunogenicity of polymerizable peptides derived from Sm32 to select potential protective epitopes. Sm32 prediction of T and B epitopes and homology studies with human legumain were performed. Among the variety of factors that influence the antibody response, we specifically examined the effect of: (i) genetic background of mouse strain, inbred (C57BL/6) versus outbred (Swiss) mice; and (ii) vaccination with a single peptide versus pool of peptides. Swiss mice raised antibodies to three different regions of the Sm32, as tested by the Multiple Antigen Blot Assay (MABA): 182-215 (peptides IMT-70 and 72), 244-273 (IMT-64) and 336-355 (IMT-66). None of these regions were immunogenic for C57BL/6. On the contrary, other peptides, IMT-4 (21-40), IMT-12 (101-120) and IMT-26 (292-313) were highly immunogenic for this inbred strain. Only Swiss mice immunized with a single peptide (IMT-64 and 72) or with three different pools of IMT-peptides (Pool A-II: 14, 16, 18, 70, 72, 89; pool A-III: 22, 64, 24, 26, 28 and pool A-V: 64, 66, 28, 70, 72) recognized the original protein in a crude extract of the worm antigen by Western blot. Peptides IMT-64, 14 and 26 were responsible for this recognition. In general, the vaccination with pool of peptides was more immunogenic for both mouse strains. Predicted B cell epitopes, with hydrophilicity scores over +10 (IMT-12, 64, 26) were always immunogenic after either single or combined peptide vaccination. Sm32 sequences 41-80 (IMT-6 and 8), 141-160 (IMT-16) and 182-215 (IMT-70 and 72) were nearly identical to the corresponding human legumain regions and should be excluded from the human vaccine. We can conclude that the regions of Sm32 that were recognized by antibodies of mice immunized with polymerizable peptides depended on the mice strain and on the hydrophilicity score of the peptides.

Amino Acid Sequence↗
PubMed2003

Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults.

The adjuvanted influenza vaccine FLUAD is composed of subunit influenza antigens combined with the MF59-adjuvant emulsion. The vaccine was developed primarily for use in elderly populations, but non-elderly individuals might also benefit. To evaluate this hypothesis, 301 healthy adults were assigned randomly to receive two intramuscular injections of either FLUAD (150 subjects) or a non-adjuvanted vaccine, Fluzone (151 subjects), in two trials conducted at a 1-year interval. Injections consisted of 15 micrograms per 0.5 ml dose. Vaccine composition was A/Texas/36/91 (H1N1), A/Johannesburg/33/94 (H3N2), and B/Harbin/7/94 for the first injection and A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2), and B/Harbin/7/94 for the second injection. Immunogenicity was evaluated at 28 and 180 days post-immunization. FLUAD was generally well tolerated in healthy adults when compared with Fluzone. FLUAD was associated with increased pain at the injection site after immunization. A statistically significant increase in the incidence of injection-site warmth, chills, myalgia, and analgesic/antipyretic use occurred in the FLUAD group after the first injection but not after the second injection. In both groups, most of these local and systemic reactions were classified as mild. FLUAD was more immunogenic than Fluzone following both injections. After the first injection, statistically significant differences were found in the percentage of subjects with four-fold rises in hemagglutinin inhibition (HI) titers at 28 days post-immunization for the B antigen. After the second injection, the FLUAD group had significantly higher HI titers, a significantly higher percentage with a four-fold increase in titer, and a significantly greater percentage of subjects with titers >/=160 for the H3N2 antigen at 28 days. Only minor immunogenicity differences between the two groups were seen at 180 days. Compared with Fluzone, FLUAD was associated with increased immunogenicity and mild post-immunization reactions in healthy adults. The magnitude of increased immunogenicity in healthy adults was less than that seen in elderly populations.

Adjuvants, Immunologic↗
PubMed1999

Multivalent group A streptococcal vaccine designed to optimize the immunogenicity of six tandem M protein fragments.

One of the major challenges in the development of group A streptococcal M protein-based vaccines is the multiplicity of M types expressed by these organisms. Previous studies have shown that multivalent vaccines containing as many as eight M protein fragments in tandem were immunogenic and evoked opsonic antibodies. It was also noted that the C-terminal fragments of these hybrid proteins were often not immunogenic or evoked only low levels of opsonic antibodies, suggesting that the C-terminus of the molecule may have been preferentially degraded or altered in vivo. In the present studies, we designed a hexavalent vaccine containing protective M protein peptides from types 24, 5, 6, 19, 1, and 3 group A streptococci. In order to "protect" the carboxy-terminal components, the amino-terminal M24 fragment was reiterated on the carboxy-terminal end of the construct. The hexavalent vaccine was immunogenic in laboratory animals and evoked high titers of antibodies against each of the native M proteins represented in the vaccine and bactericidal antibodies against all six sterotypes of group A streptococci. The vaccine was equally immunogenic when delivered in alum or in complete Freund's adjuvant. None of the immune sera contained antibodies that crossreacted with human heart tissue. Our results show that complex multivalent group A streptococcal vaccines can be designed in such a way that each M protein fragment is immunogenic and evokes protective antibodies.

Alum Compounds↗
PubMed1999

Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys.

Synthetic peptide and recombinant protein vaccines are optimally immunogenic when delivered with an effective adjuvant. Candidate vaccines currently insufficiently immunogenic may induce a protective immunity if they could be delivered with more effective adjuvants. For example, immunogens that induce promising responses when administered to mice with complete and incomplete Freund's adjuvants perform less well in primate animal models where complete Freund's adjuvant is not used. We report the use of synthetic oligodeoxynucleotides containing CpG motifs, the sequences of which are based on immunostimulatory bacterial DNA sequences, to enhance the immune response in Aotus monkeys to a synthetic peptide malaria vaccine. Monkeys were immunized with the synthetic peptide PADRE 45, a synthetic peptide containing amino acid sequences derived from the circumsporozoite protein (CSP) from Plasmodium falciparum, and delivered in an emulsion of saline and Montanide 720, a mannide oleate in oil solution, that also contained one of three oligodeoxynucleotides. The animals receiving oligodeoxynucleotides containing either three or four CpG motifs produced antibodies that bound a recombinant CSP as measured in ELISA, and reacted with P. falciparum sporozoites in a sporozoite immunofluorescent test. These responses were significantly greater than those seen in animals receiving the oligodeoxynucleotide without CpG motifs. These data indicate that oligodeoxynucleotides containing CpG motifs improve immunogenicity of peptide immunogens in non-human primates, and may be immunopotentiators useful in humans.

Adjuvants, Immunologic↗
PubMed1999

Identification of immunogenic, surface-exposed outer membrane proteins of Pasteurella haemolytica serotype 1.

Pasteurella haemolytica serotype 1 (S1) is the bacterium most frequently recovered from the lungs of cattle that have succumbed to shipping fever pneumonia. P. haemolytica outer membrane proteins (OMPs) are important immunogens in the development of resistance to pneumonic pasteurellosis. The purpose of this study was to identify the repertoire of immunogenic, surface-exposed P. haemolytica (S1) OMPs, that could be important in the development of protective immunity. We determined surface exposure of OMPs by (1) their susceptibility to protease treatment and (2) their ability to adsorb out antibodies from bovine immune sera. For a comprehensive identification of immunogenic, surface-exposed OMPs, we used bovine antisera from calves that were resistant to experimental P. haemolytica challenge after (1) natural exposure to P. haemolytica, (2) vaccination with live P. haemolytica, or (3) vaccination with P. haemolytica OMPs. We identified 21 immunogenic, surface-exposed P. haemolytica OMPs. Most were recognized by all three immune sera. However, some were recognized by one or two of the three antisera. Our analyses identified surface-exposed, immunogenic proteins that were not identified in previous studies.

Animals↗
PubMed1997

Differential immunogenicity of Epstein-Barr virus (EBV) encoded growth transformation-associated antigens in a murine model system.

The strong immunosurveillance of humans against EBV transformed immunoblasts, mediated by CD8+ cytotoxic T cells, is based on the recognition of peptides derived from eight of the nine growth transformation-associated proteins, the nuclear antigens EBNA2-6 and the membrane proteins LMP1, -2A and -2B. The ninth protein, EBNA1, required for maintenance of the viral episomes, and expressed in a cell phenotype independent manner, has not been found to generate a cytotoxic lymphocyte (CTL) response in humans. We tested whether EBNA1 has a similar immunologically privileged status in a species that has not encountered the virus in nature, the mouse. Non-immunogenic murine mammary carcinoma cells were transfected with the appropriate viral gene. Rejection responses were assayed in syngeneic mice following repeated immunisation with irradiated cells. Previously, we found that LMP1 expression in S6C, a murine mammary carcinoma of ACA (H-2f) origin, induces high rejectability, whereas corresponding EBNA1 transfectants remained non-immunogenic. In order to test whether this finding could be reproduced on another MHC class 1 background, we expressed LMP1 and EBNA1 in another non-immunogenic mammary carcinoma, SBfnHd of CBA (H-2k) origin. LMP1 but not EBNA1 transfectants were immunogenic in this system. In order to investigate whether other growth transformation-associated EBV proteins were immunogenic in the mouse, we also transfected the S6C cells with EBNA4, EBNA5, LMP2A and -2B. All four proteins induced strong rejection reactions. These findings are fully consistent with corresponding findings in the human system. They also show that the immunologically privileged status of EBNA1 is not due to some peculiarity of the long-standing co-existence between EBV and the human species, nor to any specific features of the human MHC class I system. They are consistent with the suggestion that EBNA1 may not be properly processed and/or transported, due to specific features of the protein itself.

Animals↗
PubMed1991

Brucella melitensis Rev. 1 living attenuated vaccine: stability of markers, residual virulence and immunogenicity in mice.

Five commercial Brucella melitensis Rev. 1 vaccines from different sources were compared to the original Elberg Rev. 1 strain, in vitro for classic markers and in vivo in mice, for residual virulence and immunogenicity. Because colonies of several morphology types (smooth, non-smooth) were isolated from the vaccines, representative substrains were purified to study their in vitro and in vivo activities either at once (16 strains), or after storage by subculture (12 strains) and by lyophilization (eight strains) or after passage in mice (six strains). After purification, five strains had the characteristic pattern of resistance to penicillin and streptomycin of the original strain while 11 differed by a two-fold dilution or more. A few modifications only occurred after storage or passage. Residual virulence--the time taken by 50% of the subcutaneously vaccinated mice to eradicate the strain from their spleen--or recovery time 50%, and immunogenicity--the ability of the vaccinated mice to restrict the spleen count 15 days after a virulent intraperitoneal challenge--were compared on eight strains after purification, subculture and lyophilization. After purification, one smooth strain out of five had the same activities as the original strain and three were as immunogenic but less virulent. One smooth strain and the three non-smooth were neither immunogenic nor virulent. Some strains which were typically non-smooth after purification recovered a smooth phase aspect after subculture, concomitantly with an increase in immunogenicity but not in virulence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Population genetics and the detection of immunogenic and drug-resistant loci in Plasmodium.

Host immunity will result in increased homozygosity at immunogenic loci if they encode products that elicit allele-specific immune responses. This increased homozygosity can be detected by comparison to 'neutral' (i.e. unselected) loci in the same genome which act as controls for the various epidemiological factors, such as biting rate, which affect homozygosity. Numerical results suggest that homozygosity should be 20 to 500% higher at immunogenic loci, a result which is robust to changes in host death rate and the degree of linkage between the immunogenic and neutral loci. The same logic applies to loci which encode drug resistance: treated individuals with resistant infections will transmit zygotes homozygous for the resistance allele. It is argued that this increased homozygosity at putative immunogenic loci can act as a diagnostic feature to test using field data. The method also serves as a potentially very powerful method of identifying immunogenic and drug-resistant loci in laboratory studies of species such as the murine malaria Plasmodium chabaudi.

Alleles↗
PubMedDate not supplied

A peptide carrier with a built-in vaccine adjuvant: construction of immunogenic conjugates.

A multifunctional carrier combining B/T cell epitopes (i), a built-in vaccine adjuvant (ii), and a universal T cell epitope (iii) for the construction of potent and specific immunogenic conjugates is presented. The IL-1beta(163-171) fragment known to reproduce the immunostimulatory and adjuvant effects of the whole IL-1beta without possessing any of the pro-inflammatory properties of IL-1beta was covalently anchored to the N-terminus of the Sequential Oligopeptide Carrier, SOC(n), formed by the repeating tripeptide unit Lys-Aib-Gly. A promiscuous T cell epitope derived from the tetanus toxin, TT(593-599), was also positioned in the carboxy terminus of SOC(n) as a universal immunogen to provide broad immunogenicity. Selected B/T cell epitopes from the Sm and La/SSB autoantigens, against which is directed the humoral autoimmunity in patients with systemic lupus erythematosus and Sjögren's Syndrome, respectively, were coupled to the Lys-N(epsilon)H2 groups of the carrier, and the formulated constructs were administered in animals following the conventional immunization protocol of complete/incomplete Freund's adjuvant. The induced immune responses were compared with that produced when the Sm- and La/SSB-reconstituted immunogenic conjugates were injected alone. High titers of specific antibodies recognizing the priming construct, as well as the cognate autoantigen, were obtained when administered alone without the assistance of Freund's adjuvant. It is concluded that our approach provides the conceptual and experimental framework for the development of multifunctional immunogenic conjugates eliciting enhanced, specific, and prolonged humoral response for usage as human vaccine candidates.

Adjuvants, Immunologic↗
PubMed2002

A parallel approach to the discovery of carrier delivery vehicles to enhance antigen immunogenicity.

As part of an ongoing effort to generate human and murine monoclonal antibodies against poorly immunogenic tumor-associated antigens we have merged the rapidly expanding disciplines of parallel polymer synthesis and controlled-release technology with immunology to produce a rapid and generic approach to improve the immunogenicity of carrier-bound antigens. The process involves three stages: An array of cross-linked hydrogel materials containing a carrier protein (at various concentrations) is prepared in parallel in one step. The array is then screened in mice to determine the most effective hydrogel at enhancing the immunogenicity of the encapsulated versus nonencapsulated carrier. Finally, the most efficient hydrogel is prepared containing the critical carrier-antigen conjugate and is used for immunization protocols. The strategy was successful for the BSA-glycoconjugate of the tumor-associated antigen GM3 analogue 4. When encapsulated within the hydrogel array member most efficient at elevating BSA immunogenicity, the BSA-4 glycoconjugate was significantly more immunogenic that when administered as a free antigen.

Animals↗
PubMed2004

Structure-immunogenicity relationships of therapeutic proteins.

As more recombinant human proteins become available on the market, the incidence of immunogenicity problems is rising. The antibodies formed against a therapeutic protein can result in serious clinical effects, such as loss of efficacy and neutralization of the endogenous protein with essential biological functions. Here we review the literature on the relations between the immunogenicity of the therapeutic proteins and their structural properties. The mechanisms by which protein therapeutics can induce antibodies as well as the models used to study immunogenicity are discussed. Examples of how the chemical structure (including amino acid sequence, glycosylation, and pegylation) can influence the incidence and level of antibody formation are given. Moreover, it is shown that physical degradation (especially aggregation) of the proteins as well as chemical decomposition (e.g., oxidation) may enhance the immune response. To what extent the presence of degradation products in protein formulations influences their immunogenicity still needs further investigation. Immunization of transgenic animals, tolerant for the human protein, with well-defined, artificially prepared degradation products of therapeutic proteins may shed more light on the structure-immunogenicity relationships of recombinant human proteins.

Animals↗
PubMed1981

Non-immunogenicity of enucleated rat hepatoma cells in syngeneic animals.

Cytoplasts and karyoplasts were obtained by ultracentrifugation of Hepatoma D23 cells on a Ficoll gradient containing cytochalasin B. Their nuclear and protein content and their metabolic activity were determined. Three i.p. injections of 2.3 x 10(7) cytoplasts were unable to protect syngeneic WAB/Not rats against an s.c. challenge of 10(4) D23 cells, whereas a similar amount of karyoplasts, or 3 injections of 10(6) irradiated D23 cells, were fully protective. Ability of cytoplasts to act as primary or secondary immunogen were also studied, and compared to that of 0.01% glutaraldehyde-treated cells, 43 degrees C heat-treated cells and 3M KCl-soluble extracts, these preparations also being of weak immunogenicity. Only heat-treated cells behaved as a primary immunogen, whereas none of the preparations provided a secondary stimulation. Moreover, when these preparations were fed in vitro to peritoneal-exudate cells before their injection into rats, cytoplasts and glutaraldehyde-treated cells showed no immunogenicity, whereas heat-treated cells induced full protection against tumour challenge. Therefore, in this tumour model, the in vivo persistence of immunogen and the presence of a nucleus are likely to be crucial in inducing transplantation resistance to tumour.

Animals↗
PubMed1975

Immunogenicity of Escherichia coli O antigen in upper urinary tract infection.

The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated. Heat-killed vaccines were prepared from "immunogenic" organisms which had produced upper urinary tract infection associated with high titers of hemagglutinating antibody to O antigen and "nonimmunogenic" organisms which had produced upper urinary tract infection without a rise in antibody titer. "Immunogenic" 06 vaccine produced high titers of antibody in patients regarded as possibly "poor producers" of antibody, but "nonimmunogenic" 011 vaccine was not associated with a rise in titer in patients previously regarded as "good producers". These vaccines were significantly different in immunogenicity (P less than 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P less than 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper tract infection.

Adult↗
PubMed2006

A role for protein misfolding in immunogenicity of biopharmaceuticals.

For largely unknown reasons, biopharmaceuticals evoke potentially harmful antibody formation. Such antibodies can inhibit drug efficacy and, when directed against endogenous proteins, cause life-threatening complications. Insight into the mechanisms by which biopharmaceuticals break tolerance and induce an immune response will contribute to finding solutions to prevent this adverse effect. Using a transgenic mouse model, we here demonstrate that protein misfolding, detected with the use of tissue-type plasminogen activator and thioflavin T, markers of amyloid-like properties, results in breaking of tolerance. In wild-type mice, misfolding enhances protein immunogenicity. Several commercially available biopharmaceutical products were found to contain misfolded proteins. In some cases, the level of misfolded protein was found to increase upon storage under conditions prescribed by the manufacturer. Our results indicate that misfolding of therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity. These findings offer novel possibilities to detect immunogenic protein entities with tPA and reduce immunogenicity of biopharmaceuticals.

Animals↗
PubMed2006

Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis.

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenic, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design.

Animals↗
PubMed1999

Preliminary evaluation of human immunodeficiency virus type 1 (HIV-1) immunogen in children with HIV-1 infection.

The safety and preliminary activity of human immunodeficiency virus type 1 (HIV-1) immunogen were evaluated in 10 HIV-1-infected children with disease stage N1,2 or A1,2. Multiple inoculations of 2. 5 or 10 units (U) of HIV-1 immunogen were safe and well tolerated without an acceleration of disease progression. When antiretroviral agents were coadministered, the 10 U dose appeared to be associated with more sustained reduction in plasma HIV-1 RNA than the 2.5 U dose (median log10 HIV-1 RNA at month 18, 3.07 vs. 4.01 copies/mL in 10 U [n=4] vs. 2.5 U [n=3], respectively; P=.034). Levels of regulated-on-activation, normal T cell-expressed and -secreted chemokine produced from HIV-1 immunogen-stimulated lymphocytes in vitro were increased in the children who had HIV-1 immunogen-specific antibody responses (P<.02) and appeared to be inversely correlated with levels of plasma HIV-1 RNA (P<.01). These preliminary data warrant larger studies to determine the effectiveness of adjunctive therapy with HIV-1 immunogen in children with HIV-1 infection.

AIDS Vaccines↗
PubMed1999

Heat shock protein expression in target cells infected with low levels of replication-competent virus contributes to the immunogenicity of adenoviral vectors.

A significant limitation of adenoviral vectors is their associated immunogenicity. Since we, and others, have shown that the immunogenicity of cells can be increased by the induction of heat shock proteins (hsp), and because infection with several viruses induces hsp, we investigated whether the immunogenicity of adenoviral gene transfer might be mediated through induction of hsp expression. Neither plasmid DNA nor a recombinant retroviral vector induced hsp expression in transduced B16 melanoma cells. However, hsp70 was upregulated after infection with two of six adenoviral vectors; this induction of hsp70 did not correlate with the adenoviral transgene or with the viral backbone (Ad2 or Ad5). In previous assays, no replication-competent adenovirus (RCA) had been detected in any of these viruses. However, using sensitive assays for RCA, induction of hsp70 was found to correlate with the transfer of E1A and low levels of RCA. Moreover, target cells expressing hsp70 at levels similar to those induced by RCA infection protected syngeneic mice against rechallenge with parental cells, demonstrating that cells induced to express hsp70 by inadvertant transfer of RCA will become immunogenic. These results reveal a novel mechanism contributing to the immunogenicity of adenoviral vectors. If careful screening for RCA is not used when using laboratory-prepared viral stocks, the validity of the resulting experimental data might be significantly affected, especially when the immune stimulatory effects of the transgene are being studied.

Adenoviruses, Human↗
PubMed2003

Humanization of predicted T-cell epitopes reduces the immunogenicity of chimeric antibodies: new evidence supporting a simple method.

Genetic engineering has provided several approaches to reduce immunogenicity of murine antibodies. We described previously a new method based on the humanization of the linear epitopes presented to T cells. In brief, potential immunogenic epitopes in the variable region were identified and subjected to point mutations to make them human and/or to modify amphipatic motifs. The resulting recombinant antibody retained its antigen binding affinity and was less immunogenic in monkeys than their murine or chimeric predecessors are. The present study provides two new examples of this T-cell epitope humanization approach: ior-t1A murine monoclonal antibody (mMAb), which recognizes the human-CD6 molecule, and ior-C5 mMAb, which recognizes a novel glycoprotein expressed on the surface of malignant colorectal cells. Seven amino acids were substituted in ior-C5 and eleven residues in ior-t1A, by the corresponding residues from the highest homologous human sequences. Surprisingly, the homology between re-shaped chimeric antibody variable region frameworks and human sequences was 80-90%. Experiments in monkeys showed that T1AhT and C5hT "detopes" antibodies were less immunogenic than their chimeric analogues while they retained 30-50% of antigen binding affinities. The proposed method might be of general applicability to reduce immunogenicity of chimeric antibodies with therapeutic potential.

Algorithms↗