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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. (Biokemi)
The Public Health Agency of Sweden, Stockholm, Sweden.
Karolinska Institute, Stockholm, Sweden.
Örebro University Hospital, Örebro, Sweden.ORCID iD: 0000-0002-4522-3078
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2012 (English)In: Molecular farming: plants as a production platform for high value proteins : FA action COST FA0804 / [ed] Herta Steinkellner, Bryssel: COST , 2012, p. 47-47Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
Bryssel: COST , 2012. p. 47-47
National Category
Plant Biotechnology
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:oru:diva-24331OAI: oai:DiVA.org:oru-24331DiVA, id: diva2:543780
Conference
Molecular farming, Vienna 16-17th February 2012
Projects
Molekylärt jordbrukUtveckling av slemhinneadministrerade vacciner
Note

Human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immune deficiency syndrome (AIDS), is a severe sexually transmitted infection (STI) that is implicated in one of the world’s most severe human epidemics. In 2009, approximately 33 million individuals globally were estimated to be living with HIV-1, and to date, at least 25 million people have succumbed to AIDS-related diseases. Resource-poor settings, especially the sub-Saharan region, are struggling the most with the HIV-1 epidemic. Since the beginning of the HIV-1 epidemic, a period of almost 30 years, substantial efforts have been directed at developing a protective vaccine against HIV-1 infection, with unsuccessful results. Because of the capability of HIV-1 to transfer genetic information to the genome of the infected host and its extensive capability to mutate, the development of a vaccine has been a much more complex issue than initially thought.

Several vaccine strategies have been explored in animal systems and in human trials in the quest for an HIV-1 vaccine. A somewhat neglected approach for the administration of vaccines is to target the large number of immune competent cells present in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. A subunit vaccine system capable of exposing the vaccine antigen to the GALT is believed to be the basis of a potential vaccination strategy, especially when working with STIs. Furthermore, for HIV-1 in particular, the GALT vaccination site is promising because early HIV-1 infection is associated with a rapid depletion of CD4+ immune cells in the GALT.

The use of edible transgenic plants as a production system for the p24 antigen followed by oral delivery has among others been reported by our group to successfully produce systemic immune responses in mice [1]. Briefly, transgenic Arabidopsis expressing low levels of p24 antigen was established and generated in an initially limited pilot feeding experiment in mice, and detectable levels of antip24-IgG antibodies were found in serum. In addition, a priming effect was also shown in a subsequent feeding experiment using fresh p24 transgenic plants. This was followed by the development of improved transgenic Arabidopsis containing increased levels of the p24 antigen and in transgenic Daucus carota (carrot), which also expressed the p24 antigen [2].

In the present study, we used these two HIV-1 p24 transgenic plant systems (Arabidopsis and carrot), 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 indicated that low p24 antigen doses were superior to high p24 antigen doses.

[1] Lindh et al. (2008) Feeding of mice with Arabidopsis thaliana expressing the HIV-1 subtype C p24 antigen gives rise to systemic immune response. APMIS 116:985-994

[2] Lindh et al. (2009) Production of the p24 capsid protein from HIV-1 subtype C in Arabidopsis thaliana and Daucus carota using an endoplasmic reticulum-directing SEKDEL sequence in protein expression constructs. Prot. Expr. Pur. 66:46-51

Available from: 2012-08-09 Created: 2012-08-09 Last updated: 2018-05-09Bibliographically approved

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Lindh, IngridAndersson, SörenStrid, Åke

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