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Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses
Örebro University, School of Science and Technology.
Örebro University, School of Science and Technology.ORCID iD: 0000-0003-3315-8835
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4+ T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 p24 antigen, which is released by immune competent cells in the GALT during oral administration, are interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific-IgG in sera after an intramuscular p24 protein boost. Initial dose-dependent antigen analyses using transgenic Arabidopsis thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses. No detectable levels of faecal IgA antibodies or cellular immune responses were observed.

National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:oru:diva-17314OAI: oai:DiVA.org:oru-17314DiVA, id: diva2:442792
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Plant-produced STI vaccine antigens with special emphasis on HIV-1 p24
Open this publication in new window or tab >>Plant-produced STI vaccine antigens with special emphasis on HIV-1 p24
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Objective: To establish stable transgenic non-toxic plants as a platform for plant-based vaccine production as well as potential oral delivery system of vaccine antigens for sexually transmitted infections (STIs). The concept is to immunize the mucosal immune system present in the gut-associated lymphoid tissues (GALT). HIV-1 p24 subtype C protein has been used as the main antigen model, in parallel with an engineered unique chimeric MOMP antigen from Chlamydia trachomatis serovar E.

Methods: Chimeric MOMP and p24 vaccine antigens were successfully inserted into the nuclear genomes of Arabidopsis thaliana and Daucus carota via Agrobacterium-mediated gene transfer. The characteristics of the genetic inserts and corresponding mRNAs and recombinant proteins in planta were described using several methods, including northern, Southern, and western blotting, ELISA, and a commercial HIV Ag/Ab combination assay. Immunogenicity of the antigens was studied in mice models.

Results: Transgenes of both plant species expressing p24 or chimeric MOMP were successfully generated. Additional HIV-1 vaccine antigen candidates were introduced and the genetic inserts have been confirmed in Arabidopsis thaliana. The Arabidopsis thaliana expressing p24 and chimeric MOMP were demonstrated to be stable over generations and antigenicity analyses showed that plant-derived HIV-1 p24 and chimeric MOMP retained immunological epitopes when they were expressed in planta. Oral administration of transgenic plant material generated a priming effect of the immune competent cells present in the GALT, shown by the presence of antigen-specific-IgG in mice sera after boosting. Mice immunized with plant-derived HIV-1 p24 antigen were also analyzed for antigen-specific faecal IgA as well as cellular immune responses. However, detectable levels of the two latter immune responses were not observed. The Chlamydia trachomatis chimeric MOMP antigen was further evaluated for its potential as a vaccine antigen candidate, with positive results indicating a more rapid clearance of the Chlamydia trachomatis infection post immunization.

Conclusion: Stable non-toxic transgenic plants expressing either HIV-1 p24 or a novel  Chlamydia trachomatis chimeric MOMP antigens have successfully been developed. The two plant-produced STI vaccine antigens have in initial mice feeding studies provided important proof-of-concept for the oral vaccination approach. Now, immunization studies to expand, en-hance, and improve knowledge of the immune responses generated by the orally delivered transgenic plants are of high priority.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2011. p. 86
Series
Örebro Studies in Life Science ; 8
Keywords
Plant-based vaccines, Arabidopsis thaliana, HIV-1, p24, GALT, mucosal immunity, Chlamydia trachomatis, MOMP, Daucus carota
National Category
Chemical Sciences
Research subject
Chemistry
Identifiers
urn:nbn:se:oru:diva-17242 (URN)978-91-7668-817-5 (ISBN)
Public defence
2011-10-28, Hörsal M, Örebro universitet, Fakultetsgatan 1, Örebro, 10:15 (English)
Opponent
Supervisors
Projects
Kemi/biokemi
Available from: 2011-09-13 Created: 2011-09-13 Last updated: 2017-10-17Bibliographically approved

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Lindh, IngridStrid, Åke

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