α1-giardin based live heterologous vaccine protects against Giardia lamblia infection in a murine model
Open accessAbstract
Giardia lamblia is a leading protozoan cause of diarrheal disease worldwide, yet preventive medical strategies are not available. A crude veterinary vaccine has been licensed for cats and dogs, but no defined human vaccine is available. We tested the vaccine potential of three conserved antigens previously identified in human and murine giardiasis, α1-giardin, α-enolase, and ornithine carbamoyl transferase, in a murine model of G. lamblia infection. Live recombinant attenuated Salmonella enterica Serovar Typhimurium vaccine strains were constructed that stably expressed each antigen, maintained colonization capacity, and sustained total attenuation in the host. Oral administration of the vaccine strains induced antigen-specific serum IgG, particularly IgG(2A), and mucosal IgA for α1-giardin and α-enolase, but not for ornithine carbamoyl transferase. Immunization with the α1-giardin vaccine induced significant protection against subsequent G. lamblia challenge, which was further enhanced by boosting with cholera toxin or sublingual α1-giardin administration. The α-enolase vaccine afforded no protection. Analysis of α1-giardin from divergent assemblage A and B isolates of G. lamblia revealed >97% amino acid sequence conservation and immunological cross-reactivity, further supporting the potential utility of this antigen in vaccine development. Together. These results indicate that α1-giardin is a suitable candidate antigen for a vaccine against giardiasis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Immunization with a live, recombinant alpha-1 giardin vaccine formulation provided protection from a Giardia challenge in a murine model.
“immunization with a live, recombinant alpha-1 giardin vaccine formulation provided protection from a Giardia challenge in a murine model (8).”
From Comparative Cell Biology and Evolution of Annexins in Diplomonads (2016) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Annexin-like alpha giardins: a new cytoskeletal gene family in Giardia lamblia
Weiland, M. E.-L., McArthur, A. G., Morrison, H. G., Sogin, M. L., & Svärd, S. G. (2005) · International Journal for Parasitology · doi:10.1016/j.ijpara.2004.12.009 · Cited by 93 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 58
- [1]Karanis P Kourenti C Smith H Waterborne transmission of protozoan parasites: a worldwide review of outbreaks and lessons learnt J Water Health 2007 5 1 38 17402277
- [2]Majewska AC Successful experimental infections of a human volunteer and Mongolian gerbils with Giardia of animal origin Trans R Soc Trop Med Hyg 1994 88 360 2 7974691
- [3]Nash TE Herrington DA Losonsky GA Levine MM Experimental human infections with Giardia lamblia J Infect Dis 1987 156 974 84 3680997
- [4]Flanagan PA Giardia--diagnosis, clinical course and epidemiology. A review Epidemiol Infect 1992 109 1 22 1499664 PMC2272232
- [5]Buret AG Pathophysiology of enteric infections with Giardia duodenalius Parasite 2008 15 261 5 18814692
- [6]Olson ME Ceri H Morck DW Giardia vaccination Parasitol Today 2000 16 213 7 10782082
- [7]Uehlinger FD O’Handley RM Greenwood SJ Guselle NJ Gabor LJ Van Velsen CM Efficacy of vaccination in preventing giardiasis in calves Vet Parasitol 2007 146 182 8 17350765 PMC7126623
- [8]Abdul-Wahid A Faubert G Characterization of the local immune response to cyst antigens during the acute and elimination phases of primary murine giardiasis Int J Parasitol 2008 38 691 703 18037419
- [9]Larocque R Nakagaki K Lee P Abdul-Wahid A Faubert GM Oral immunization of BALB/c mice with Giardia duodenalis recombinant cyst wall protein inhibits shedding of cysts Infect Immun 2003 71 5662 9 14500486 PMC201086
- [10]Lee P Abdul-Wahid A Faubert GM Comparison of the local immune response against Giardia lamblia cyst wall protein 2 induced by recombinant Lactococcus lactis and Streptococcus gordonii Microbes Infect 2009 11 20 8 18992359
- [11]Abdul-Wahid A Faubert G Mucosal delivery of a transmission-blocking DNA vaccine encoding Giardia lamblia CWP2 by Salmonella typhimurium bactofection vehicle Vaccine 2007 25 8372 83 17996337
- [12]Faubert G Immune response to Giardia duodenalis Clin Microbiol Rev 2000 13 35 54 table of contents 10627490 PMC88932
- [13]Nash TE Surface antigenic variation in Giardia lamblia Mol Microbiol 2002 45 585 90 12139606
- [14]Singer SM Elmendorf HG Conrad JT Nash TE Biological selection of variant-specific surface proteins in Giardia lamblia J Infect Dis 2001 183 119 24 11087204
- [15]Bienz M Siles-Lucas M Wittwer P Muller N vsp gene expression by Giardia lamblia clone GS/M-83-H7 during antigenic variation in vivo and in vitro Infect Immun 2001 69 5278 85 11500396 PMC98636
- [16]Prucca CG Slavin I Quiroga R Elias EV Rivero FD Saura A Antigenic variation in Giardia lamblia is regulated by RNA interference Nature 2008 456 750 4 19079052
- [17]Rivero FD Saura A Prucca CG Carranza PG Torri A Lujan HD Disruption of antigenic variation is crucial for effective parasite vaccine Nat Med 2010 16 551 7 1p following 57 20418884
- [18]Morrison HG McArthur AG Gillin FD Aley SB Adam RD Olsen GJ Genomic minimalism in the early diverging intestinal parasite Giardia lamblia Science 2007 317 1921 6 17901334
- [19]Franzen O Jerlstrom-Hultqvist J Castro E Sherwood E Ankarklev J Reiner DS Draft genome sequencing of giardia intestinalis assemblage B isolate GS: is human giardiasis caused by two different species? PLoS Pathog 2009 5 e1000560 19696920 PMC2723961
- [20]Palm JE Weiland ME Griffiths WJ Ljungstrom I Svard SG Identification of immunoreactive proteins during acute human giardiasis J Infect Dis 2003 187 1849 59 12792861
- [21]Tellez A Palm D Weiland M Aleman J Winiecka-Krusnell J Linder E Secretory antibodies against Giardia intestinalis in lactating Nicaraguan women Parasite Immunol 2005 27 163 9 15987339
- [22]Davids BJ Palm JE Housley MP Smith JR Andersen YS Martin MG Polymeric immunoglobulin receptor in intestinal immune defense against the lumen-dwelling protozoan parasite Giardia J Immunol 2006 177 6281 90 17056558
- [23]Curtiss R 3rd Bacterial infectious disease control by vaccine development J Clin Invest 2002 110 1061 6 12393839 PMC150804
- [24]Ebensen T Guzman CA Immune modulators with defined molecular targets: cornerstone to optimize rational vaccine design Hum Vaccin 2008 4 13 22 18376145
- [25]Perrie Y Mohammed AR Kirby DJ McNeil SE Bramwell VW Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens Int J Pharm 2008 364 272 80 18555624
- [26]Cheminay C Hensel M Rational design of Salmonella recombinant vaccines Int J Med Microbiol 2008 298 87 17888730
- [27]Stager S Gottstein B Muller N Systemic and local antibody response in mice induced by a recombinant peptide fragment from Giardia lamblia variant surface protein (VSP) H7 produced by a Salmonella typhimurium vaccine strain Int J Parasitol 1997 27 965 71 9292314
- [28]Byrd LG Conrad JT Nash TE Giardia lamblia infections in adult mice Infect Immun 1994 62 3583 5 8039934 PMC302999
- [29]Boreham PF Phillips RE Shepherd RW The sensitivity of Giardia intestinalis to drugs in vitro J Antimicrob Chemother 1984 14 449 61 6511706
- [30]Capon AG Upcroft JA Boreham PF Cottis LE Bundesen PG Similarities of Giardia antigens derived from human and animal sources Int J Parasitol 1989 19 91 8 2651342
- [31]Li Y Wang S Xin W Scarpellini G Shi Z Gunn B A sopB deletion mutation enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines Infect Immun 2008 76 5238 46 18765737 PMC2573344
- [33]Kang HY Srinivasan J Curtiss R 3rd Immune responses to recombinant pneumococcal PspA antigen delivered by live attenuated Salmonella enterica serovar typhimurium vaccine Infect Immun 2002 70 1739 49 11895935 PMC127874
- [34]Hitchcock PJ Brown TM Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels J Bacteriol 1983 154 269 77 6187729 PMC217456
- [35]Ringqvist E Palm JE Skarin H Hehl AB Weiland M Davids BJ Release of metabolic enzymes by Giardia in response to interaction with intestinal epithelial cells Mol Biochem Parasitol 2008 159 85 91 18359106 PMC3658456
- [36]Raghavan S Ostberg AK Flach CF Ekman A Blomquist M Czerkinsky C Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the stomach Infect Immun 2010 78 4251 60 20696831 PMC2950356
- [37]von Allmen N Bienz M Hemphill A Muller N Experimental infections of neonatal mice with cysts of Giardia lamblia clone GS/M-83-H7 are associated with an antigenic reset of the parasite Infect Immun 2004 72 4763 71 15271938 PMC470631
- [38]Rahn K De Grandis SA Clarke RC McEwen SA Galan JE Ginocchio C Amplification of an invA gene sequence of Salmonella typhimurium by polymerase chain reaction as a specific method of detection of Salmonella Mol Cell Probes 1992 6 271 9 1528198
- [39]Monis PT Andrews RH Mayrhofer G Ey PL Molecular systematics of the parasitic protozoan Giardia intestinalis Mol Biol Evol 1999 16 1135 44 10486969
- [40]Larkin MA Blackshields G Brown NP Chenna R McGettigan PA McWilliam H Clustal W and Clustal X version 2. 0 Bioinformatics 2007 23 2947 8 17846036
- [41]Curtiss R 3rd Xin W Li Y Kong W Wanda SY Gunn B New technologies in using recombinant attenuated Salmonella vaccine vectors Crit Rev Immunol 2010 30 255 70 20370633 PMC3970581
- [42]Wang S Li Y Scarpellini G Kong W Shi H Baek CH Salmonella vaccine vectors displaying delayed antigen synthesis in vivo to enhance immunogenicity Infect Immun 2010 78 3969 80 20605977 PMC2937466
- [43]Singer SM Nash TE T-cell-dependent control of acute Giardia lamblia infections in mice Infect Immun 2000 68 170 5 10603384 PMC97117
- [44]Vinayak VK Kum K Khanna R Khuller M Systemic-oral immunization with 56 kDa molecule of Giardia lamblia affords protection in experimental mice Vaccine 1992 10 21 7 1539457
- [45]Langford TD Housley MP Boes M Chen J Kagnoff MF Gillin FD Central importance of immunoglobulin A in host defense against Giardia spp Infect Immun 2002 70 11 8 11748158 PMC127595
- [46]Sulaiman IM Fayer R Bern C Gilman RH Trout JM Schantz PM Triosephosphate isomerase gene characterization and potential zoonotic transmission of Giardia duodenalis Emerg Infect Dis 2003 9 1444 52 14718089 PMC3035538
- [47]Buret AG Mechanisms of epithelial dysfunction in giardiasis Gut 2007 56 316 7 17339241 PMC1856818
- [48]Gaucher D Chadee K Prospect for an Entamoeba histolytica Gal-lectin-based vaccine Parasite Immunol 2003 25 55 8 12791100
- [50]Peattie DA Alonso RA Hein A Caulfield JP Ultrastructural localization of giardins to the edges of disk microribbons of Giarida lamblia and the nucleotide and deduced protein sequence of alpha giardin J Cell Biol 1989 109 2323 35 2808530 PMC2115877
- [51]Jenkins MC O’Brien CN Murphy C Schwarz R Miska K Rosenthal B Antibodies to the ventral disc protein delta-giardin prevent in vitro binding of Giardia lamblia trophozoites J Parasitol 2009 95 895 9 19702359
- [52]Weiland ME Palm JE Griffiths WJ McCaffery JM Svard SG Characterisation of alpha-1 giardin: an immunodominant Giardia lamblia annexin with glycosaminoglycan-binding activity Int J Parasitol 2003 33 1341 51 14527517
- [53]Veiga-Malta I Duarte M Dinis M Tavares D Videira A Ferreira P Enolase from Streptococcus sobrinus is an immunosuppressive protein Cell Microbiol 2004 6 79 88 14678332
- [54]Pancholi V Fischetti VA alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci J Biol Chem 1998 273 14503 15 9603964
- [55]Andersen YS Gillin FD Eckmann L Adaptive immunity-dependent intestinal hypermotility contributes to host defense against Giardia spp Infect Immun 2006 74 2473 6 16552082 PMC1418922
- [56]Montagnoli C Sandini S Bacci A Romani L La Valle R Immunogenicity and protective effect of recombinant enolase of Candida albicans in a murine model of systemic candidiasis Med Mycol 2004 42 319 24 15473356
- [57]Xin W Wanda SY Li Y Wang S Mo H Curtiss R 3rd Analysis of type II secretion of recombinant pneumococcal PspA and PspC in a Salmonella enterica serovar Typhimurium vaccine with regulated delayed antigen synthesis Infect Immun 2008 76 3241 54 18458067 PMC2446722
- [58]Eko FO He Q Brown T McMillan L Ifere GO Ananaba GA A novel recombinant multisubunit vaccine against Chlamydia J Immunol 2004 173 3375 82 15322201
- [59]Kong W Wanda SY Zhang X Bollen W Tinge SA Roland KL Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment Proc Natl Acad Sci U S A 2008 105 9361 6 18607005 PMC2453710
- [60]Yang X Hinnebusch BJ Trunkle T Bosio CM Suo Z Tighe M Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and V antigens protects against bubonic and pneumonic plague J Immunol 2007 178 1059 67 17202369 PMC9809976
Cited by
Sorted by citations
Advances in understanding Giardia: Determinants and mechanisms of chronic sequelae
Bartelt, L. A., & Sartor, R. B. (2015) · F1000Prime Reports · doi:10.12703/p7-62 · Cited by 154 · see citing works
A genome-wide analysis of annexins from parasitic organisms and their vectors
Cantacessi, C., Seddon, J. M., Miller, T. L., Leow, C. Y., Thomas, L., Mason, L., Willis, C., Walker, G., Loukas, A., Gasser, R. B., et al. (2013) · Scientific Reports · doi:10.1038/srep02893 · Cited by 46 · see citing works
Comparative Cell Biology and Evolution of Annexins in Diplomonads
Einarsson, E., Ástvaldsson, Á., Hultenby, K., Andersson, J. O., Svärd, S. G., & Jerlström-Hultqvist, J. (2016) · mSphere · doi:10.1128/msphere.00032-15 · Cited by 15 · see citing works
Self-citation
- Authors
- Jenikova, G., Hruz, P., Andersson, M. K., Tejman-Yarden, N., Ferreira, P. C. D., Andersen, Y. S., Davids, B. J., Gillin, F. D., Svärd, S. G., Curtiss, R., & Eckmann, L.
- Affiliations
- University of California San Diego (US)
- Uppsala University (SE)
- Arizona State University (US)
- Corresponding author
- Eckmann, Lars
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 29
- Issue
- 51
- Pages
- 9529-9537
- ISSN
- 0264-410X (ISSN-L)
- PMC
- PMC4045459
- OpenAlex
- W2073178782
- Cited by
- 49
- References
- 1
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 6 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DK35108, DK80506, AI60557, AI56289)
- Swedish Research Council
- Sweden-America Foundation
- FAPESP (São Paulo Reasearch Foundation)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Parasitic Infections and Diagnostics
- Health Sciences › Medicine › Infectious Diseases › Amoebic Infections and Treatments
- Health Sciences › Medicine › Infectious Diseases › Viral gastroenteritis research and epidemiology
- Keywords
- Giardia lamblia, giardiasis, live attenuated vaccine, alpha-enolase, ornithine carbamoyltransferase, vaccine candidate antigens, mucosal IgA, sublingual immunization, immunological cross-reactivity, mouse model
- MeSH terms
- Administration, Oral, Animals, Antibodies, Protozoan, Antigens, Protozoan, Cholera Toxin, Cytoskeletal Proteins, Giardiasis, Mice, Inbred BALB C, Ornithine Carbamoyltransferase, Phosphopyruvate Hydratase, Salmonella typhimurium, Vaccines, Synthetic, Protozoan Proteins, Protozoan Vaccines, Giardia lamblia, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review