Increasing Efficacy of Enveloped Whole-Virus Vaccines by In situ Immune-Complexing with the Natural Anti-Gal Antibody Increased immunogenicity of glycoengineered whole-virus vaccines
Main Article Content
Abstract
The appearance of variants of mutated virus in course of the Covid-19 pandemic raises concerns regarding the risk of possible formation of variants that can evade the protective immune response elicited by the single antigen S-protein gene-based vaccines. This risk may be avoided by inclusion of several antigens in vaccines, so that a variant that evades the immune response to the S-protein of SARS-CoV-2 virus will be destroyed by the protective immune response against other viral antigens. A simple way for preparing multi-antigenic enveloped-virus vaccines is using the inactivated whole-virus as vaccine. However, immunogenicity of such vaccines may be suboptimal because of poor uptake of the vaccine by antigen-presenting-cells (APC) due to electrostatic repulsion by the negative charges of sialic-acid on both the glycan-shield of the vaccinating virus and on the carbohydrate-chains (glycans) of APC. In addition, glycan-shield can mask many antigenic peptides. These effects of the glycan-shield can be reduced and immunogenicity of the vaccinating virus markedly increased by glycoengineering viral glycans for replacing sialic-acid units on glycans with a-gal epitopes (Gala1-3Galb1-4GlcNAc-R). Vaccination of humans with inactivated whole-virus presenting a-gal epitopes (virusa-gal) results in formation of immune-complexes with the abundant natural anti-Gal antibody that binds to viral a-gal epitopes at the vaccination site. These immune-complexes are targeted to APC for rigorous uptake due to binding of the Fc portion of immunocomplexed anti-Gal to Fcg receptors on APC. The APC further transport the large amounts of internalized vaccinating virus to regional lymph nodes, process and present the virus antigenic peptides for the activation of many clones of virus specific helper and cytotoxic T-cells. This elicits a protective cellular and humoral immune response against multiple viral antigens and an effective immunological memory. The immune response to virusa-gal vaccine was studied in mice producing anti-Gal and immunized with inactivated influenza-virusa-gal. These mice demonstrated 100-fold increase in titer of the antibodies produced, a marked increase in T-cell response, and a near complete protection against challenge with a lethal dose of live influenza-virus, in comparison to a similar vaccine lacking a-gal epitopes. This glycoengineering can be achieved in vitro by enzymatic reaction with neuraminidase removing sialic-acid and with recombinant a1,3galactosyltransferase (a1,3GT) synthesizing a-gal epitopes, by engineering host-cells to contain several copies of the a1,3GT gene (GGTA1), or by transduction of this gene in a replication-defective adenovirus vector into host-cells. Theoretically, these methods for increased immunogenicity may be applicable to all enveloped viruses with N-glycans on their envelope.
Keywords:
Inactivated whole-virus vaccine, vaccine immunogenicity, a-gal epitope, natural anti-Gal antibody, glycan-shield, enveloped virus vaccines, variants
Article Details
How to Cite
GALILI, Uri.
Increasing Efficacy of Enveloped Whole-Virus Vaccines by In situ Immune-Complexing with the Natural Anti-Gal Antibody.
Medical Research Archives, [S.l.], v. 9, n. 7, july 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2481>. Date accessed: 22 nov. 2024.
doi: https://doi.org/10.18103/mra.v9i7.2481.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Lauring AS, Hodcroft EB. Genetic Variants of SARS-CoV-2-What Do They Mean? JAMA. 2021;325:529-531. PMID: 33404586
2. Borrow P, Lewicki H, Wei X, et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med. 1997; 3:205-211. PMID: 9018240.
3. Wei X, Decker JM, Wang S, et al. Antibody neutralization and escape by HIV-1. Nature. 2003;422:307-312. PMID: 12646921
4. Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 1990;265:10373-10382. PMID: 2355006.
5. Mizuochi, T, Matthews T, Kato M, et al. Diversity of oligosaccharide structures on the envelope glycoprotein gp120 of human immunodeficiency virus 1 from the lymphoblastoid cell line H9. Presence of complex-type oligosaccharides with bisecting N-acetylglucosamine residues. J Biol Chem. 1990;265:8519-8524. PMID: 2341393.
6. Watanabe Y, Bowden TA, Wilson IA, Crispin M. Exploitation of glycosylation in enveloped virus pathobiology. Biochim Biophys Acta Gen Subj. 2019;1863:1480-1497. PMID: 31121217.
7. Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science 2020;369:330-333. PMID: 32366695.
8. Walls AC, Tortorici MA, Frenz B, et al. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nat Struct Mol Biol. 2016;23,899-905. PMID: 27617430.
9. Bagdonaite I, Thompson AJ, Wang X, et al. Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells. Viruses 2021;13:551. PMID: 33806155.
10. Galili U. Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. Vaccine. 2020 ;38:6487-6499. PMID: 32907757.
11. Goulder,PJ, Watkins DI. HIV and SIV CTL escape: implications for vaccine design. Nat. Rev. Immunol. 4, 630–640. PMID: 15286729.
12. Lewis GK, DeVico AL, Gallo RC. Antibody persistence and T-cell balance: two key factors confronting HIV vaccine development. Proc Natl Acad Sci USA 2014;111:15614–15621. PMID: 25349379.
13. Galili U, Korkesh A, Kahane I, Rachmilewitz EA. Demonstration of a natural antigalactosyl IgG antibody on thalassemic red blood cells. Blood 1983;61:1258-1264. PMID: 6839023.
14. Galili U, Rachmilewitz EA, Peleg A, Flechner IA. A unique natural human IgG antibody with anti-α-galactosyl specificity. J Exp Med. 1984;160:1519-1531. PMID: 6491603.
15. Galili U, Mandrell RE, Hamadeh RM, Shohet SB, Griffiss JM. Interaction between human natural anti--galactosyl immunoglobulin G and bacteria of the human flora. Infect Immun. 1988;56:1730-1737. PMID: 6839023.
16. Posekany,KJ, Pittman HK, Bradfield JF, Haisch CE, Verbanac KM. Induction of cytolytic anti-Gal antibodies in -1,3-galactosyltransferase gene knockout mice by oral inoculation with Escherichia coli O86:B7 bacteria. Infect Immun. 2002;70:6215-6222. PMID: 12379700.
17. Mañez R, Blanco FJ, Díaz I, et al. Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural a-galactosyl IgG antibodies. Xenotransplantation 2001;8:15-23. PMID: 12379700.
18. Galili U. Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits. Immunology 2013;140:1-11. PMID: 23578170.
19. Hamadeh RM, Galili U, Zhou P, Griffiss JM. Anti--galactosyl immunoglobulin A (IgA), IgG, and IgM in human secretions. Clin Diagn Lab Immunol. 1995;2:125-131. PMID: 7697518.
20. Avila JL, Rojas M, Galili U. Immunogenic Galα1-3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania. J Immunol. 1989;142: 2828-2834. PMID: 2467941.
21. McMorrow IM, Comrack CA, Sachs DH, DerSimonian H. Heterogeneity of human anti-pig natural antibodies cross-reactive with the Gal(α1,3)Galactose epitope. Transplantation 1997;64: 501-510. PMID: 9275119.
22. Galili U, Macher BA, Buehler J, Shohet SB. Human natural anti--galactosyl IgG. II. The specific recognition of (1-3)-linked galactose residues. J Exp Med 1985;162:573-582. PMID: 2410529.
23. Towbin H, Rosenfelder G, Wieslander J, et al. Circulating antibodies to mouse laminin in Chagas disease, American cutaneous leishmaniasis, and normal individuals recognize terminal galactosyl(1-3)-galactose epitopes. J Exp Med. 1987;166:419-432. PMID: 2439642.
24. Teneberg S, Lönnroth I, Torres Lopez JF, et al. Molecular mimicry in the recognition of glycosphingolipids by Galα3Galß4GlcNAcß-binding Clostridium difficile toxin A, human natural anti-α-galactosyl IgG and the monoclonal antibody Gal-13: characterization of a binding-active human glycosphingolipid, non-identical with the animal receptor. Glycobiology 1996;6:599-609. PMID: 8922955.
25. Galili U, Clark MR, Shohet SB, Buehler J, Macher BA. Evolutionary relationship between the anti-Gal antibody and the Gal1-3Gal epitope in primates. Proc Natl Acad Sci USA. 1987;84:1369-1373. PMID: 2434954.
26. Galili U, Shohet SB, Kobrin E, Stults CLM, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of α-galactosyl epitopes on nucleated cells. J Biol Chem. 1988;263:17755-17762. PMID: 2460463.
27. Spiro RG, Bhoyroo VD. Occurrence of -D-galactosyl residues in the thyroglobulin from several species. Localization in the saccharide chains of the complex carbohydrate units. J Biol Chem. 1984;259:9858-9866. PMID: 6086655.
28. Thall A, Galili U. Distribution of Gal1-3Gal1-4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay. Biochemistry 1990;29:3959-3965. PMID: 2354167.
29. Oriol R, Candelier JJ, Taniguchi S, et al. Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research. Xenotransplantation 1999; 6:79-89. PMID: 10431784.
30. Basu M, Basu S. Enzymatic synthesis of blood group related pentaglycosyl ceramide by an α-galactosyltransferase. J Biol Chem. 1973;248:1700-1706. PMID: 4632915.
31. Betteridge A, Watkins WM. Two α-3-D galactosyltransferases in rabbit stomach mucosa with different acceptor substrate specificities. Eur J Biochem. 1983;132: 29-35. PMID: 6404630.
32. Blake DD, Goldstein IJ. An α-D-galactosyltransferase in Ehrlich ascites tumor cells: biosynthesis and characterization of a trisaccharide (α-D-galacto(1-3)-N-acetyllactosamine). J Biol Chem. 1981;256: 5387-5393. PMID: 6787040.
33. Blanken WM, van den Eijnden DH. Biosynthesis of terminal Galα1-3Galß1-4GlcNAc-R oligosaccharide sequence on glycoconjugates: purification and acceptor specificity of a UDP-Gal: N-acetyllactosamine α1,3galactosyltransferase. J Biol Chem. 1985;260:12927-12934. PMID: 3932335.
34. Teranishi K, Manez R, Awwad M, Cooper DK. Anti-Gal α1-3Gal IgM and IgG antibody levels in sera of humans and old world non-human primates. Xenotransplantation 2002;9:148-154. PMID: 11897007.
35. Larsen RD, Rajan VP, Ruff MM, Kukowska-Latallo J, Cummings D, Lowe JB. Isolation of a cDNA encoding a murine UDP- galactose:β-D-galactosyl-1,4-N-acetyl-D-glucosaminide α-1,3-galactosyltransferase: expression cloning by gene transfer. Proc Natl Acad Sci USA. 1989;86:8227-8231. PMID: 2510162.
36. Joziasse DH, Shaper JH, Van den Eijnden DH, Van Tunen AH, Shaper NL. Bovine α1-3- galactosyltransferase: isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA. J Biol Chem. 1989;264:14290-14297. PMID: 2503516.
37. Henion TR, Macher BA, Anaraki F, Galili U. Defining the minimal size of catalytically active primate α1,3galactosyltransferase: Structure function studies on the recombinant truncated enzyme. Glycobiology 1994;4:193-201. PMID: 8054718.
38. Larsen RD, Rivera-Marrero CA, Ernst LK, Cummings RD, Lowe JB. Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:β-D-Gal(1,4)-D-GlcNAc α(1,3)- galactosyltransferase cDNA. J Biol Chem. 1990;265:7055-7061. PMID: 8054718.
39. Galili U, Swanson K. Gene sequences suggest inactivation of α1-3 galactosyltransferase in catarrhines after the divergence of apes from monkeys. Proc Natl Acad Sci USA. 1991;88:7401-7404. PMID: 1908095.
40. Koike C, Fung JJ, Geller DA, et al., Molecular basis of evolutionary loss of the α1,3-galactosyltransferase gene in higher primates. J Biol Chem. 2002;277:10114-10120. PMID: 11773054.
41. Lantéri M, Giordanengo V, Vidal F, Gaudray P, Lefebvre J-C. A complete α1,3-galactosyltransferase gene is present in the human genome and partially transcribed. Glycobiology 2002;12:785-792. PMID: 12499400.
42. Galili U. Evolution in primates by "Catastrophic-selection" interplay between enveloped virus epidemics, mutated genes of enzymes synthesizing carbohydrate antigens, and natural anti-carbohydrate antibodies. Am J Phys Anthropol. 2019;168:352-363. PMID: 30578545.
43. Repik PM, Strizki M, Galili U. Differential host dependent expression of α-galactosyl epitopes on viral glycoproteins: A study of Eastern equine encephalitis virus as a model. J Gen Virol. 1994; 75:1177-1181. PMID: 7513744.
44. Galili U, Repik PM, Anaraki F, Mozdzanowska K, Washko G, Gerhard W. Enhancement of antigen presentation of influenza virus hemagglutinin by the natural anti-Gal antibody. Vaccine 1996;14:321-328. PMID: 8744560.
45. Geyer R, Geyer H, Stirm S, et al. Major oligosaccharides in the glycoprotein of Friend murine leukemia virus: Structure elucidation by one and two-dimensional proton nuclear magnetic resonance and methylation analysis. Biochemistry 1984; 23:5628-5637. PMID: 6439245.
46. Rother RP, Fodor WL, Springhorn JP, et al. A novel mechanism of retrovirus inactivation in human serum mediated by anti-α-galactosyl natural antibody. J Exp Med. 1995:182:1345-1355. PMID: 7595205.
47. Takeuchi Y, Porter CD, Strahan KM, et al. Sensitization of cells and retroviruses to human serum by (α1-3) galactosyltransferase. Nature 1996;379:85-88. PMID: 16715304.
48. Takeuchi Y, Liong SH, Bieniasz PD, et al. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl(α1-3)galactosylation. J Virol. 1997:71: 6174-6178. PMID: 9223512.
49. Welsh RM, O’Donnell CL, Reed DJ, Rother RP. Evaluation of the Galα1-3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses. J Virol. 1998;72: 4650-4656. PMID: 9573228.
50. Pipperger L, Koske I, Wild N, et al. Xenoantigen-dependent complement-mediated neutralization of LCMV glycoprotein pseudotyped VSV in human serum. J Virol. 2019;93:e00567-19. PMID: 31243134.
51. Preece AF, Strahan KM, Devitt J, Yamamoto F, Gustafsson K. Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement. Blood 2002;99:2477-2482. PMID: 11895782.
52. Kim NY, Jung WW, Oh YK, et al. Natural protection from zoonosis by α-gal epitopes on virus particles in xenotransmission. Xenotransplantation 2007, 14, 104–111. PMID: 17381684.
53. Galili U. Host synthesized carbohydrate antigens on viral glycoproteins as "Achilles' Heel" of viruses contributing to anti-viral immune protection. Int J Mol Sci. 2020;21:6702. PMID: 32933166.
54. Webster RG. Immunity to influenza in the elderly. Vaccine 2000;18:1686-1689. PMID: 10689149.
55. Chang YT, Guo CY, Tsai MS, et al. Poor immune response to a standard single dose non-adjuvanted vaccination against 2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis patients. Vaccine 2012;30:5009-5018. PMID: 22658967.
56. Houston WE, Kremer RJ, Crabbs CL, Spertzel RO. Inactivated Venezuelan equine encephalomyelitis virus vaccine complexed with specific antibody: enhanced primary immune response and altered pattern of antibody class elicited. J Infect Dis. 1977;135:600-610. PMID: 404363.
57. Celis E, Chang TW. Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen. Science 1984;224:297-299. PMID: 6231724.
58. Villinger F, Mayne AE, Bostik P, Mori K, Jensen PE, Ahmed R. Evidence for antibody-mediated enhancement of simian immunodeficiency virus (SIV) Gag antigen processing and cross presentation in SIV-infected rhesus macaques. J Virol. 2003;77:10-24. PMID: 12477806.
59. Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV. Fc receptors are required in passive and active immunity to melanoma. Proc Natl Acad Sci USA. 1998;95:652-656. PMID: 9435247.
60. Galili U, LaTemple DC. Natural anti-Gal antibody as a universal augmenter of autologous tumor vaccine immunogenicity. Immunol Today. 1997;18:281-285. PMID: 9190114.
61. Regnault A, Lankar D, Lacabanne V, et al. Fc receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med. 1999;189:371-380. PMID: 9892619.
62. Schuurhuis DH, Ioan-Facsinay A, Nagelkerken B, van Schip JJ, Sedlik C, Melief CJ. Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8+ CTL responses in vivo. J Immunol. 2002;168:2240-2246. PMID: 11859111.
63. Abdel-Motal U, Wang S, Lu S, Wigglesworth K, Galili U. Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Gal1-3Gal1-4GlcNAc-R epitopes. J Virol. 2006;80:6943-6951. PMID: 16809300.
64. Abdel-Motal UM, Guay HM, Wigglesworth K, Welsh RM, Galili U. Immunogenicity of influenza virus vaccine is increased by anti-Gal-mediated targeting to antigen-presenting cells. J Virol. 2007;81:9131-9141. PMID: 17609270.
65. Dürrbach, A.; Baple, E.; Preece, A.F.; Charpentier, B.; Gustafsson, K. Virus recognition by specific natural antibodies and complement results in MHC I cross-presentation. J Immunol. 2007; 37:1254-1265. PMID: 17407191.
66. Thall AD, Malý P, Lowe JB. Oocyte Galα1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. J Biol Chem. 1995;270:21437-21440. PMID: 7545161.
67. Tanemura M, Yin D, Chong AS, Galili U. Differential immune responses to -gal epitopes on xenografts and allografts: implications for accommodation in xenotransplantation. J Clin Invest. 2000;105:301-310. PMID: 10675356.
68. Tanemura M, Maruyama S, Galili U. Differential expression of α-gal epitopes (Galα1-3Galß1-4GlcNAc-R) on pig and mouse organs. Transplantation 2012;69:187-190. PMID: 10653403.
69. Rötzschke O, Falk K, Stevanović S, Jung G, Walden P, Rammensee HG. Exact prediction of a natural T cell epitope. Eur J Immunol. 1991;21:2891-2894. PMID: 1718764.
70. Galili U, Wigglesworth K, Abdel-Motal UM. Intratumoral injection of -gal glycolipids induces xenograft-like destruction and conversion of lesions into endogenous vaccines. J Immunol. 2007;178:4676-4687. PMID: 17372027.
71. Abdel-Motal UM, Wigglesworth K, Galili U. Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody. Vaccine 2009;27:3072-3082. PMID: 19428921.
72. Shastri N, Gonzalez F. Endogenous generation and presentation of the ovalbumin peptide/Kb complex to T cells. J Immunol. 1993;150:2724-2736. PMID: 8454852.
73. Sanderson S, Shastri N. LacZ inducible, antigen/MHC-specific T cell hybrids. Int Immunol. 1994;6:369-376. PMID: 8186188.
74. Chen ZC, Tanemura M, Galili U. Synthesis of α-gal epitopes (Gal1-3Galß1-4GlcNAc-R) on human tumor cells by recombinant 1,3galactosyltransferase produced in Pichia pastoris. Glycobiology 2001;11:577-586. PMID: 11447137.
75. Henion TR, Gerhard W, Anaraki F, Galili, U. Synthesis of α-gal epitopes on influenza virus vaccines, by recombinant α1,3galactosyltransferase, enables the formation of immune complexes with the natural anti-Gal antibody. Vaccine 1997;15,1174-1182. PMID: 32907757.
76. Yan LM, Lau SPN, Poh CM, et al. Heterosubtypic protection induced by a live attenuated influenza virus vaccine expressing Galactose-α-1,3-Galactose epitopes in infected cells. mBio 2020; 11: e00027-20. PMID: 32127444.
77. Abdel-Motal UM, Wang S, Awad A, Lu S, Wigglesworth K, Galili U. Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing -gal epitopes. Vaccine 2010;28:1758-1765. PMID: 20034607.
78. Benatuil L, Kaye J, Rich RF, Fishman JA, Green WR, Iacomini J. The influence of natural antibody specificity on antigen immunogenicity. Eur J Immunol. 2005;35:2638-2647. PMID: 16082726.
79. Kratzer RF, Espenlaub S, Hoffmeister A, Kron MW, Kreppel F. Covalent decoration of adenovirus vector capsids with the carbohydrate epitope αGal does not improve vector immunogenicity but allows to study the in vivo fate of adenovirus immunocomplexes. PLoS One 2017;12:e0176852. PMID: 28472163.
80. Galili U. Autologous tumor vaccines processed to express a-gal epitopes: a practical approach to immunotherapy in cancer. Cancer Immunol Immunother. 2004;53:935-945. PMID: 29077749.
81. Qiu Y, Xu MB, Yun MM, et al. Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells. World J Gastroenterol. 2011;17:5260-5266. PMID: 22219594.
82. Qiu Y, Yun MM, Xu MB, Wang YZ, Yun S. Pancreatic carcinoma-specific immunotherapy using synthesized -galactosyl epitope-activated immune responders: findings from a pilot study. Int J Clin Oncol. 2013;18:657-665. PMID: 22847800.
83. Smith DF, Larsen RD, Mattox S, Lowe JB, Cummings RD. Transfer and expression of a murine UDP-Gal-D-Gal-1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. J Biol Chem. 1990;265:6225-6234. PMID: 2108155.
84. LaTemple DC, Abrams JT, Zhang, Galili U. Increased immunogenicity of tumor vaccines complexed with anti-Gal: Studies in knock out mice for 1,3galactosyltranferase. Cancer Res. 1999; 59: 3417-3423. PMID: 10416604.
85. Rossi GR, Mautino MR, Unfer RC, Seregina TM, Vahanian N, Link CJ. Effective treatment of preexisting melanoma with whole cell vaccines expressing (1,3)-galactosyl epitopes. Cancer Res. 2005;65:10555-10561. PMID: 16288048.
86. Deriy L, Chen ZC, Gao GP, Galili U. Expression of -gal epitopes on HeLa cells transduced with adenovirus containing 1,3galactosyltransferase cDNA. Glycobiology 2002;12:135‐144. PMID: 11886847.
87. Deriy L, Ogawa H, Gao GP, Galili U. In vivo targeting of vaccinating tumor cells to antigen-presenting cells by a gene therapy method with adenovirus containing the α-1,3-galactosyltransferase gene. Cancer Gene Ther. 2005;12:528-539. PMID: 15818383.
88. Whalen GF, Sullivan M, Piperdi B, Wasseff W, Galili U. Cancer immunotherapy by intratumoral injection of α-gal glycolipids. Anticancer Res. 2012;32:3861-3868. PMID: 22993330.
89. Albertini MR, Ranheim EA, Zuleger CL, et al. Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma. Cancer Immunol Immunother. 2016;65:897-907. PMID: 27207605.
90. Qiu Y, Yun MM, Dong X, et al. Combination of cytokine-induced killer and dendritic cells pulsed with antigenic α-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy. Cytotherapy 2016;18:91-98. PMID: 27207605.
91. Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013;13:354-359. PMID: 23743512.
92. Levin M, Apostolovic D, Biedermann T, et al. Galactose α-1,3-galactose phenotypes: Lessons from various patient populations. Ann Allergy Asthma Immunol. 2019;122:598-602. PMID: 30922956.
93. Pollack K, Zlotoff BJ, Borish LC, Commins SP, Platts-Mills TAE, Wilson JM. α-Gal Syndrome vs Chronic Urticaria. JAMA Dermatol. 2019;155:115-116. PMID: 30476954
2. Borrow P, Lewicki H, Wei X, et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med. 1997; 3:205-211. PMID: 9018240.
3. Wei X, Decker JM, Wang S, et al. Antibody neutralization and escape by HIV-1. Nature. 2003;422:307-312. PMID: 12646921
4. Leonard CK, Spellman MW, Riddle L, Harris RJ, Thomas JN, Gregory TJ. Assignment of intrachain disulfide bonds and characterization of potential glycosylation sites of the type 1 recombinant human immunodeficiency virus envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells. J Biol Chem 1990;265:10373-10382. PMID: 2355006.
5. Mizuochi, T, Matthews T, Kato M, et al. Diversity of oligosaccharide structures on the envelope glycoprotein gp120 of human immunodeficiency virus 1 from the lymphoblastoid cell line H9. Presence of complex-type oligosaccharides with bisecting N-acetylglucosamine residues. J Biol Chem. 1990;265:8519-8524. PMID: 2341393.
6. Watanabe Y, Bowden TA, Wilson IA, Crispin M. Exploitation of glycosylation in enveloped virus pathobiology. Biochim Biophys Acta Gen Subj. 2019;1863:1480-1497. PMID: 31121217.
7. Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science 2020;369:330-333. PMID: 32366695.
8. Walls AC, Tortorici MA, Frenz B, et al. Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy. Nat Struct Mol Biol. 2016;23,899-905. PMID: 27617430.
9. Bagdonaite I, Thompson AJ, Wang X, et al. Site-Specific O-Glycosylation Analysis of SARS-CoV-2 Spike Protein Produced in Insect and Human Cells. Viruses 2021;13:551. PMID: 33806155.
10. Galili U. Amplifying immunogenicity of prospective Covid-19 vaccines by glycoengineering the coronavirus glycan-shield to present α-gal epitopes. Vaccine. 2020 ;38:6487-6499. PMID: 32907757.
11. Goulder,PJ, Watkins DI. HIV and SIV CTL escape: implications for vaccine design. Nat. Rev. Immunol. 4, 630–640. PMID: 15286729.
12. Lewis GK, DeVico AL, Gallo RC. Antibody persistence and T-cell balance: two key factors confronting HIV vaccine development. Proc Natl Acad Sci USA 2014;111:15614–15621. PMID: 25349379.
13. Galili U, Korkesh A, Kahane I, Rachmilewitz EA. Demonstration of a natural antigalactosyl IgG antibody on thalassemic red blood cells. Blood 1983;61:1258-1264. PMID: 6839023.
14. Galili U, Rachmilewitz EA, Peleg A, Flechner IA. A unique natural human IgG antibody with anti-α-galactosyl specificity. J Exp Med. 1984;160:1519-1531. PMID: 6491603.
15. Galili U, Mandrell RE, Hamadeh RM, Shohet SB, Griffiss JM. Interaction between human natural anti--galactosyl immunoglobulin G and bacteria of the human flora. Infect Immun. 1988;56:1730-1737. PMID: 6839023.
16. Posekany,KJ, Pittman HK, Bradfield JF, Haisch CE, Verbanac KM. Induction of cytolytic anti-Gal antibodies in -1,3-galactosyltransferase gene knockout mice by oral inoculation with Escherichia coli O86:B7 bacteria. Infect Immun. 2002;70:6215-6222. PMID: 12379700.
17. Mañez R, Blanco FJ, Díaz I, et al. Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural a-galactosyl IgG antibodies. Xenotransplantation 2001;8:15-23. PMID: 12379700.
18. Galili U. Anti-Gal: an abundant human natural antibody of multiple pathogeneses and clinical benefits. Immunology 2013;140:1-11. PMID: 23578170.
19. Hamadeh RM, Galili U, Zhou P, Griffiss JM. Anti--galactosyl immunoglobulin A (IgA), IgG, and IgM in human secretions. Clin Diagn Lab Immunol. 1995;2:125-131. PMID: 7697518.
20. Avila JL, Rojas M, Galili U. Immunogenic Galα1-3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania. J Immunol. 1989;142: 2828-2834. PMID: 2467941.
21. McMorrow IM, Comrack CA, Sachs DH, DerSimonian H. Heterogeneity of human anti-pig natural antibodies cross-reactive with the Gal(α1,3)Galactose epitope. Transplantation 1997;64: 501-510. PMID: 9275119.
22. Galili U, Macher BA, Buehler J, Shohet SB. Human natural anti--galactosyl IgG. II. The specific recognition of (1-3)-linked galactose residues. J Exp Med 1985;162:573-582. PMID: 2410529.
23. Towbin H, Rosenfelder G, Wieslander J, et al. Circulating antibodies to mouse laminin in Chagas disease, American cutaneous leishmaniasis, and normal individuals recognize terminal galactosyl(1-3)-galactose epitopes. J Exp Med. 1987;166:419-432. PMID: 2439642.
24. Teneberg S, Lönnroth I, Torres Lopez JF, et al. Molecular mimicry in the recognition of glycosphingolipids by Galα3Galß4GlcNAcß-binding Clostridium difficile toxin A, human natural anti-α-galactosyl IgG and the monoclonal antibody Gal-13: characterization of a binding-active human glycosphingolipid, non-identical with the animal receptor. Glycobiology 1996;6:599-609. PMID: 8922955.
25. Galili U, Clark MR, Shohet SB, Buehler J, Macher BA. Evolutionary relationship between the anti-Gal antibody and the Gal1-3Gal epitope in primates. Proc Natl Acad Sci USA. 1987;84:1369-1373. PMID: 2434954.
26. Galili U, Shohet SB, Kobrin E, Stults CLM, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of α-galactosyl epitopes on nucleated cells. J Biol Chem. 1988;263:17755-17762. PMID: 2460463.
27. Spiro RG, Bhoyroo VD. Occurrence of -D-galactosyl residues in the thyroglobulin from several species. Localization in the saccharide chains of the complex carbohydrate units. J Biol Chem. 1984;259:9858-9866. PMID: 6086655.
28. Thall A, Galili U. Distribution of Gal1-3Gal1-4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay. Biochemistry 1990;29:3959-3965. PMID: 2354167.
29. Oriol R, Candelier JJ, Taniguchi S, et al. Major carbohydrate epitopes in tissues of domestic and African wild animals of potential interest for xenotransplantation research. Xenotransplantation 1999; 6:79-89. PMID: 10431784.
30. Basu M, Basu S. Enzymatic synthesis of blood group related pentaglycosyl ceramide by an α-galactosyltransferase. J Biol Chem. 1973;248:1700-1706. PMID: 4632915.
31. Betteridge A, Watkins WM. Two α-3-D galactosyltransferases in rabbit stomach mucosa with different acceptor substrate specificities. Eur J Biochem. 1983;132: 29-35. PMID: 6404630.
32. Blake DD, Goldstein IJ. An α-D-galactosyltransferase in Ehrlich ascites tumor cells: biosynthesis and characterization of a trisaccharide (α-D-galacto(1-3)-N-acetyllactosamine). J Biol Chem. 1981;256: 5387-5393. PMID: 6787040.
33. Blanken WM, van den Eijnden DH. Biosynthesis of terminal Galα1-3Galß1-4GlcNAc-R oligosaccharide sequence on glycoconjugates: purification and acceptor specificity of a UDP-Gal: N-acetyllactosamine α1,3galactosyltransferase. J Biol Chem. 1985;260:12927-12934. PMID: 3932335.
34. Teranishi K, Manez R, Awwad M, Cooper DK. Anti-Gal α1-3Gal IgM and IgG antibody levels in sera of humans and old world non-human primates. Xenotransplantation 2002;9:148-154. PMID: 11897007.
35. Larsen RD, Rajan VP, Ruff MM, Kukowska-Latallo J, Cummings D, Lowe JB. Isolation of a cDNA encoding a murine UDP- galactose:β-D-galactosyl-1,4-N-acetyl-D-glucosaminide α-1,3-galactosyltransferase: expression cloning by gene transfer. Proc Natl Acad Sci USA. 1989;86:8227-8231. PMID: 2510162.
36. Joziasse DH, Shaper JH, Van den Eijnden DH, Van Tunen AH, Shaper NL. Bovine α1-3- galactosyltransferase: isolation and characterization of a cDNA clone. Identification of homologous sequences in human genomic DNA. J Biol Chem. 1989;264:14290-14297. PMID: 2503516.
37. Henion TR, Macher BA, Anaraki F, Galili U. Defining the minimal size of catalytically active primate α1,3galactosyltransferase: Structure function studies on the recombinant truncated enzyme. Glycobiology 1994;4:193-201. PMID: 8054718.
38. Larsen RD, Rivera-Marrero CA, Ernst LK, Cummings RD, Lowe JB. Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:β-D-Gal(1,4)-D-GlcNAc α(1,3)- galactosyltransferase cDNA. J Biol Chem. 1990;265:7055-7061. PMID: 8054718.
39. Galili U, Swanson K. Gene sequences suggest inactivation of α1-3 galactosyltransferase in catarrhines after the divergence of apes from monkeys. Proc Natl Acad Sci USA. 1991;88:7401-7404. PMID: 1908095.
40. Koike C, Fung JJ, Geller DA, et al., Molecular basis of evolutionary loss of the α1,3-galactosyltransferase gene in higher primates. J Biol Chem. 2002;277:10114-10120. PMID: 11773054.
41. Lantéri M, Giordanengo V, Vidal F, Gaudray P, Lefebvre J-C. A complete α1,3-galactosyltransferase gene is present in the human genome and partially transcribed. Glycobiology 2002;12:785-792. PMID: 12499400.
42. Galili U. Evolution in primates by "Catastrophic-selection" interplay between enveloped virus epidemics, mutated genes of enzymes synthesizing carbohydrate antigens, and natural anti-carbohydrate antibodies. Am J Phys Anthropol. 2019;168:352-363. PMID: 30578545.
43. Repik PM, Strizki M, Galili U. Differential host dependent expression of α-galactosyl epitopes on viral glycoproteins: A study of Eastern equine encephalitis virus as a model. J Gen Virol. 1994; 75:1177-1181. PMID: 7513744.
44. Galili U, Repik PM, Anaraki F, Mozdzanowska K, Washko G, Gerhard W. Enhancement of antigen presentation of influenza virus hemagglutinin by the natural anti-Gal antibody. Vaccine 1996;14:321-328. PMID: 8744560.
45. Geyer R, Geyer H, Stirm S, et al. Major oligosaccharides in the glycoprotein of Friend murine leukemia virus: Structure elucidation by one and two-dimensional proton nuclear magnetic resonance and methylation analysis. Biochemistry 1984; 23:5628-5637. PMID: 6439245.
46. Rother RP, Fodor WL, Springhorn JP, et al. A novel mechanism of retrovirus inactivation in human serum mediated by anti-α-galactosyl natural antibody. J Exp Med. 1995:182:1345-1355. PMID: 7595205.
47. Takeuchi Y, Porter CD, Strahan KM, et al. Sensitization of cells and retroviruses to human serum by (α1-3) galactosyltransferase. Nature 1996;379:85-88. PMID: 16715304.
48. Takeuchi Y, Liong SH, Bieniasz PD, et al. Sensitization of rhabdo-, lenti-, and spumaviruses to human serum by galactosyl(α1-3)galactosylation. J Virol. 1997:71: 6174-6178. PMID: 9223512.
49. Welsh RM, O’Donnell CL, Reed DJ, Rother RP. Evaluation of the Galα1-3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses. J Virol. 1998;72: 4650-4656. PMID: 9573228.
50. Pipperger L, Koske I, Wild N, et al. Xenoantigen-dependent complement-mediated neutralization of LCMV glycoprotein pseudotyped VSV in human serum. J Virol. 2019;93:e00567-19. PMID: 31243134.
51. Preece AF, Strahan KM, Devitt J, Yamamoto F, Gustafsson K. Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement. Blood 2002;99:2477-2482. PMID: 11895782.
52. Kim NY, Jung WW, Oh YK, et al. Natural protection from zoonosis by α-gal epitopes on virus particles in xenotransmission. Xenotransplantation 2007, 14, 104–111. PMID: 17381684.
53. Galili U. Host synthesized carbohydrate antigens on viral glycoproteins as "Achilles' Heel" of viruses contributing to anti-viral immune protection. Int J Mol Sci. 2020;21:6702. PMID: 32933166.
54. Webster RG. Immunity to influenza in the elderly. Vaccine 2000;18:1686-1689. PMID: 10689149.
55. Chang YT, Guo CY, Tsai MS, et al. Poor immune response to a standard single dose non-adjuvanted vaccination against 2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis patients. Vaccine 2012;30:5009-5018. PMID: 22658967.
56. Houston WE, Kremer RJ, Crabbs CL, Spertzel RO. Inactivated Venezuelan equine encephalomyelitis virus vaccine complexed with specific antibody: enhanced primary immune response and altered pattern of antibody class elicited. J Infect Dis. 1977;135:600-610. PMID: 404363.
57. Celis E, Chang TW. Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen. Science 1984;224:297-299. PMID: 6231724.
58. Villinger F, Mayne AE, Bostik P, Mori K, Jensen PE, Ahmed R. Evidence for antibody-mediated enhancement of simian immunodeficiency virus (SIV) Gag antigen processing and cross presentation in SIV-infected rhesus macaques. J Virol. 2003;77:10-24. PMID: 12477806.
59. Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV. Fc receptors are required in passive and active immunity to melanoma. Proc Natl Acad Sci USA. 1998;95:652-656. PMID: 9435247.
60. Galili U, LaTemple DC. Natural anti-Gal antibody as a universal augmenter of autologous tumor vaccine immunogenicity. Immunol Today. 1997;18:281-285. PMID: 9190114.
61. Regnault A, Lankar D, Lacabanne V, et al. Fc receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med. 1999;189:371-380. PMID: 9892619.
62. Schuurhuis DH, Ioan-Facsinay A, Nagelkerken B, van Schip JJ, Sedlik C, Melief CJ. Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8+ CTL responses in vivo. J Immunol. 2002;168:2240-2246. PMID: 11859111.
63. Abdel-Motal U, Wang S, Lu S, Wigglesworth K, Galili U. Increased immunogenicity of human immunodeficiency virus gp120 engineered to express Gal1-3Gal1-4GlcNAc-R epitopes. J Virol. 2006;80:6943-6951. PMID: 16809300.
64. Abdel-Motal UM, Guay HM, Wigglesworth K, Welsh RM, Galili U. Immunogenicity of influenza virus vaccine is increased by anti-Gal-mediated targeting to antigen-presenting cells. J Virol. 2007;81:9131-9141. PMID: 17609270.
65. Dürrbach, A.; Baple, E.; Preece, A.F.; Charpentier, B.; Gustafsson, K. Virus recognition by specific natural antibodies and complement results in MHC I cross-presentation. J Immunol. 2007; 37:1254-1265. PMID: 17407191.
66. Thall AD, Malý P, Lowe JB. Oocyte Galα1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. J Biol Chem. 1995;270:21437-21440. PMID: 7545161.
67. Tanemura M, Yin D, Chong AS, Galili U. Differential immune responses to -gal epitopes on xenografts and allografts: implications for accommodation in xenotransplantation. J Clin Invest. 2000;105:301-310. PMID: 10675356.
68. Tanemura M, Maruyama S, Galili U. Differential expression of α-gal epitopes (Galα1-3Galß1-4GlcNAc-R) on pig and mouse organs. Transplantation 2012;69:187-190. PMID: 10653403.
69. Rötzschke O, Falk K, Stevanović S, Jung G, Walden P, Rammensee HG. Exact prediction of a natural T cell epitope. Eur J Immunol. 1991;21:2891-2894. PMID: 1718764.
70. Galili U, Wigglesworth K, Abdel-Motal UM. Intratumoral injection of -gal glycolipids induces xenograft-like destruction and conversion of lesions into endogenous vaccines. J Immunol. 2007;178:4676-4687. PMID: 17372027.
71. Abdel-Motal UM, Wigglesworth K, Galili U. Mechanism for increased immunogenicity of vaccines that form in vivo immune complexes with the natural anti-Gal antibody. Vaccine 2009;27:3072-3082. PMID: 19428921.
72. Shastri N, Gonzalez F. Endogenous generation and presentation of the ovalbumin peptide/Kb complex to T cells. J Immunol. 1993;150:2724-2736. PMID: 8454852.
73. Sanderson S, Shastri N. LacZ inducible, antigen/MHC-specific T cell hybrids. Int Immunol. 1994;6:369-376. PMID: 8186188.
74. Chen ZC, Tanemura M, Galili U. Synthesis of α-gal epitopes (Gal1-3Galß1-4GlcNAc-R) on human tumor cells by recombinant 1,3galactosyltransferase produced in Pichia pastoris. Glycobiology 2001;11:577-586. PMID: 11447137.
75. Henion TR, Gerhard W, Anaraki F, Galili, U. Synthesis of α-gal epitopes on influenza virus vaccines, by recombinant α1,3galactosyltransferase, enables the formation of immune complexes with the natural anti-Gal antibody. Vaccine 1997;15,1174-1182. PMID: 32907757.
76. Yan LM, Lau SPN, Poh CM, et al. Heterosubtypic protection induced by a live attenuated influenza virus vaccine expressing Galactose-α-1,3-Galactose epitopes in infected cells. mBio 2020; 11: e00027-20. PMID: 32127444.
77. Abdel-Motal UM, Wang S, Awad A, Lu S, Wigglesworth K, Galili U. Increased immunogenicity of HIV-1 p24 and gp120 following immunization with gp120/p24 fusion protein vaccine expressing -gal epitopes. Vaccine 2010;28:1758-1765. PMID: 20034607.
78. Benatuil L, Kaye J, Rich RF, Fishman JA, Green WR, Iacomini J. The influence of natural antibody specificity on antigen immunogenicity. Eur J Immunol. 2005;35:2638-2647. PMID: 16082726.
79. Kratzer RF, Espenlaub S, Hoffmeister A, Kron MW, Kreppel F. Covalent decoration of adenovirus vector capsids with the carbohydrate epitope αGal does not improve vector immunogenicity but allows to study the in vivo fate of adenovirus immunocomplexes. PLoS One 2017;12:e0176852. PMID: 28472163.
80. Galili U. Autologous tumor vaccines processed to express a-gal epitopes: a practical approach to immunotherapy in cancer. Cancer Immunol Immunother. 2004;53:935-945. PMID: 29077749.
81. Qiu Y, Xu MB, Yun MM, et al. Hepatocellular carcinoma-specific immunotherapy with synthesized α1,3- galactosyl epitope-pulsed dendritic cells and cytokine-induced killer cells. World J Gastroenterol. 2011;17:5260-5266. PMID: 22219594.
82. Qiu Y, Yun MM, Xu MB, Wang YZ, Yun S. Pancreatic carcinoma-specific immunotherapy using synthesized -galactosyl epitope-activated immune responders: findings from a pilot study. Int J Clin Oncol. 2013;18:657-665. PMID: 22847800.
83. Smith DF, Larsen RD, Mattox S, Lowe JB, Cummings RD. Transfer and expression of a murine UDP-Gal-D-Gal-1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. J Biol Chem. 1990;265:6225-6234. PMID: 2108155.
84. LaTemple DC, Abrams JT, Zhang, Galili U. Increased immunogenicity of tumor vaccines complexed with anti-Gal: Studies in knock out mice for 1,3galactosyltranferase. Cancer Res. 1999; 59: 3417-3423. PMID: 10416604.
85. Rossi GR, Mautino MR, Unfer RC, Seregina TM, Vahanian N, Link CJ. Effective treatment of preexisting melanoma with whole cell vaccines expressing (1,3)-galactosyl epitopes. Cancer Res. 2005;65:10555-10561. PMID: 16288048.
86. Deriy L, Chen ZC, Gao GP, Galili U. Expression of -gal epitopes on HeLa cells transduced with adenovirus containing 1,3galactosyltransferase cDNA. Glycobiology 2002;12:135‐144. PMID: 11886847.
87. Deriy L, Ogawa H, Gao GP, Galili U. In vivo targeting of vaccinating tumor cells to antigen-presenting cells by a gene therapy method with adenovirus containing the α-1,3-galactosyltransferase gene. Cancer Gene Ther. 2005;12:528-539. PMID: 15818383.
88. Whalen GF, Sullivan M, Piperdi B, Wasseff W, Galili U. Cancer immunotherapy by intratumoral injection of α-gal glycolipids. Anticancer Res. 2012;32:3861-3868. PMID: 22993330.
89. Albertini MR, Ranheim EA, Zuleger CL, et al. Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma. Cancer Immunol Immunother. 2016;65:897-907. PMID: 27207605.
90. Qiu Y, Yun MM, Dong X, et al. Combination of cytokine-induced killer and dendritic cells pulsed with antigenic α-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy. Cytotherapy 2016;18:91-98. PMID: 27207605.
91. Commins SP, Platts-Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013;13:354-359. PMID: 23743512.
92. Levin M, Apostolovic D, Biedermann T, et al. Galactose α-1,3-galactose phenotypes: Lessons from various patient populations. Ann Allergy Asthma Immunol. 2019;122:598-602. PMID: 30922956.
93. Pollack K, Zlotoff BJ, Borish LC, Commins SP, Platts-Mills TAE, Wilson JM. α-Gal Syndrome vs Chronic Urticaria. JAMA Dermatol. 2019;155:115-116. PMID: 30476954