title: Immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic HIV protein.
abstract: Elicitation of broad humoral immune responses is a critical factor in the development of effective HIV vaccines. In an effort to develop low-cost candidate vaccines based on multiepitopic recombinant proteins, this study has been undertaken to assess and characterize the immunogenic properties of a lettuce-derived C4(V3)6 multiepitopic protein. This protein consists of V3 loops corresponding to five different HIV isolates, including MN, IIIB, RF, CC, and RU. In this study, both Escherichia coli and lettuce-derived C4(V3)6 have elicited local and systemic immune responses when orally administered to BALB/c mice. More importantly, lettuce-derived C4(V3)6 has shown a higher immunogenic potential than that of E. coli-derived C4(V3)6. Moreover, when reactivity of sera from mice immunized with C4(V3)6 are compared with those elicited by a chimeric protein carrying a single V3 sequence, broader responses have been observed. The lettuce-derived C4(V3)6 has elicited antibodies with positive reactivity against V3 loops from isolates MN, RF, and CC. In addition, splenocyte proliferation assays indicate that significant T-helper responses are induced by the C4(V3)6 immunogen. Taken together, these findings account for the observed elicitation of broader humoral responses by the C4(V3)6 multiepitopic protein. Moreover, they provide further validation for the production of multiepitopic vaccines in plant cells as this serves not only as a low-cost expression system, but also as an effective delivery vehicle for orally administered immunogens.
authors.affiliation: Laboratorio de Biofarmacéuticos recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis Potosí, Mexico.
authors.forename: Dania O
authors.initials: DO
authors.lastname: Govea-Alonso
authors.forename: Néstor
authors.initials: N
authors.lastname: Rubio-Infante
authors.forename: Ana Lilia
authors.initials: AL
authors.lastname: García-Hernández
authors.forename: Javier T
authors.initials: JT
authors.lastname: Varona-Santos
authors.forename: Schuyler S
authors.initials: SS
authors.lastname: Korban
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreno-Fierros
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosales-Mendoza
mesh_terms: D016915:AIDS Vaccines / Q000096:biosynthesis*; D000818:Animals; D004926:Escherichia coli; D005260:Female; D054298:Human Immunodeficiency Virus Proteins / Q000096:biosynthesis* / Q000276:immunology*; D055261:Immunogenetic Phenomena; D018545:Lactuca / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000096:biosynthesis; D014614:Vaccines, Synthetic / Q000096:biosynthesis
chemical_list: D016915:AIDS Vaccines; D054298:Human Immunodeficiency Virus Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic
references.citation: Plant Biotechnol J. 2008 Dec;6(9):897-913
references.pmid: 19548344
references.citation: Nature. 1984 Dec 20-1985 Jan 2;312(5996):763-7
references.pmid: 6096719
references.citation: Plant J. 2009 Jan;57(1):45-54
references.pmid: 18764920
references.citation: J Virol. 2012 Jul;86(14):7588-95
references.pmid: 22573869
references.citation: Trends Biotechnol. 2003 Dec;21(12):570-8
references.pmid: 14624867
references.citation: Plant Mol Biol. 2012 Mar;78(4-5):337-49
references.pmid: 22228408
references.citation: Virology. 2008 Mar 15;372(2):233-46
references.pmid: 18061228
references.citation: Science. 1998 Jun 19;280(5371):1884-8
references.pmid: 9632381
references.citation: Life Sci. 1999;64(21):1897-912
references.pmid: 10353588
references.citation: Clin Vaccine Immunol. 2008 May;15(5):852-8
references.pmid: 18367580
references.citation: Plant Cell Rep. 2012 Mar;31(3):495-511
references.pmid: 22159962
references.citation: Nat Med. 2009 Aug;15(8):866-70
references.pmid: 19525964
references.citation: J Immunol. 1996 Jul 1;157(1):462-72
references.pmid: 8683152
references.citation: AIDS. 2006 Oct 24;20(16):W13-23
references.pmid: 17053344
references.citation: Plant Biotechnol J. 2011 Aug;9(6):629-38
references.pmid: 21443546
references.citation: Trends Plant Sci. 2001 May;6(5):219-26
references.pmid: 11335175
references.citation: Viral Immunol. 2006 Summer;19(2):237-49
references.pmid: 16817766
references.citation: N Engl J Med. 2012 Apr 5;366(14):1275-86
references.pmid: 22475592
references.citation: Mol Immunol. 2009 May;46(8-9):1718-26
references.pmid: 19269688
references.citation: N Engl J Med. 2009 Dec 3;361(23):2209-20
references.pmid: 19843557
references.citation: BMC Biotechnol. 2008 Jun 23;8:53
references.pmid: 18573204
references.citation: PLoS One. 2010 Jan 20;5(1):e8805
references.pmid: 20098712
references.citation: Biotechnol Lett. 2006 Jul;28(13):959-67
references.pmid: 16794774
references.citation: Annu Rev Immunol. 2010;28:413-44
references.pmid: 20192810
references.citation: J Exp Med. 1989 Dec 1;170(6):2023-35
references.pmid: 2479705