A chloroplast-derived C4V3 polypeptide from the human immunodeficiency virus (HIV) is orally immunogenic in mice.
Although the human immunodeficiency virus (HIV) causes one of the most important infectious diseases worldwide, attempts to develop an effective vaccine remain elusive. Designing recombinant proteins capable of eliciting significant and protective mammalian immune responses remain a priority. Moreover, large-scale production of proteins of interest at affordable cost remains a challenge for modern biotechnology. In this study, a synthetic gene encoding a C4V3 recombinant protein, known to induce systemic and mucosal immune responses in mammalian systems, has been introduced into tobacco chloroplasts to yield high levels of expression. Integration of the transgene into the tobacco plastome has been verified by Southern blot hybridization. The recombinant C4V3 protein is also detected in tobacco chloroplasts by confocal microscopy. Reactivity of the heterologous protein with both an anti-C4V3 rabbit serum as well as sera from HIV positive patients have been assayed using Western blots. When administered by the oral route in a four-weekly dose immunization scheme, the plant-derived C4V3 has elicited both systemic and mucosal antibody responses in BALB/c mice, as well as CD4+ T cell proliferation responses. These findings support the viability of using plant chloroplasts as biofactories for HIV candidate vaccines, and could serve as important vehicles for the development of a plant-based candidate vaccine against HIV.
Laboratorio de Biofarmacéuticos Recombinantes, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210 San Luis Potosí, Mexico.
Néstor
N
Rubio-Infante
Dania O
DO
Govea-Alonso
Ángel G
ÁG
Alpuche-Solís
Ana Lilia
AL
García-Hernández
Ruth E
RE
Soria-Guerra
L M Teresita
LM
Paz-Maldonado
Damaris
D
Ilhuicatzi-Alvarado
Javier T
JT
Varona-Santos
Leticia
L
Verdín-Terán
Schuyler S
SS
Korban
Leticia
L
Moreno-Fierros
Sergio
S
Rosales-Mendoza
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000276:immunology*; D002736:Chloroplasts / Q000235:genetics* / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D030821:Plants, Genetically Modified; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D014026:Nicotiana / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D010455:Peptides; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic