Plant-produced STI vaccine antigens with special emphasis on HIV-1 p24

issn 1653-3100

isbn 978-91-7668-817-5 Örebro Studies in Life Science 8

örebro 2011

Doctoral Dissertation

Plant-produced STI vaccine antigens with special emphasis on HIV-1 p24

Ingrid Lindh Chemistry/Biochemistry

2011

In g r id L in d h Pla nt- pr od uc ed S T I v ac ci ne a nt ig en s w ith s pe ci al e m ph as is o n H IV -1 p 24

Örebro StudieS in Life Science

8

INGRID LINDH holds a M.Sc. degree in engineering biology from Linköping University. She continued as a postgraduate student in biochemistry at the Örebro Life Science Center (ÖLSC) at Örebro University, where the work of her Ph.D. thesis was performed. During her postgraduate studies, Ingrid received a scholarship for internship abroad. In 2009/2010, six months of her postgraduate studies were performed at Prof Heribert Warzecha’s laboratory at Darmstadt Technological University, Germany, where she was developing plastid transformation techniques for Arabidopsis thaliana.

The majority of pathogenic microorganisms enter their hosts via the mucosal surfaces, including the respiratory, gastrointestinal, and genital tracts. The primary protection of these tissues is the mucosal immune system, which comprise more than half of all immune competent cells in the body. Un- treated sexually transmitted infections (STIs) such as HIV-1 and Chlamydia trachomatis are dominantly observed in resource-poor settings and can lead to severe consequences including AIDS and infertility. From a global clinical and public health perspective, there is an obvious need for a cost-effective vaccine against HIV-1 and Chlamydia trachomatis. Since more traditional vaccine development strategies have not paid off, it is tempting to explore novel approaches in this research field.

The objective of this thesis was to establish stable transgenic non-toxic plants as a platform for plant-based vaccine production as well as potential oral delivery system of STI vaccine antigens. 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. The STI vaccine antigen candidates were successfully inserted into the genomes of Arabidopsis thaliana (Arabidopsis) and Daucus carota (carrot) via Agrobacterium-mediated gene transfer and production of the recombinant proteins in planta were confirmed. Oral ad- ministration 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. Now, studies to expand, enhance, and improve knowledge of the immune responses generated by the orally delivered transgenic plants are of high priority.

Ing r id L in dh Plant-produced STI vaccine antigens with special emphasis on HIV -1 p24