www.czu.cz ; www.usab-tm.ro ; www.raupp.info

Although a HIV-vaccine would be highly desirable, so far no candidate have
shown adequate efficacy when administered alone. However, a subunit vaccine
produced in plants could be the solution, March 2005 by Daniel Schneeberger,
Checkbiotech.

Vaccines present one of the most powerful and cost-effective arms of
medicine. Modern medicine?s triumphs against many horrible diseases as polio
and smallpox are mainly thanks to vaccines. A vaccine against HIV would be
highly desirable as the disease is silently spreading out of control in many
parts of the world, infecting as many as five million people last year,
while also being responsible for almost every twentieth premature death
worldwide. However, the design and development of such vaccines seems to be
very challenging.

So far none of the developed vaccine candidates have demonstrated adequate
efficacy. ?HIV is so complex that any attempt to target one step in its life
cycle is doomed to fail,? said Tsafrir Mor, Assistant Professor at the
Arizona State University.

A promising strategy to overcome this obstacle could be the combination of
multiple vaccines that target different mechanisms of infection. As
HIV-infection most commonly occurs through mucosal tissue, such a vaccine
cocktail should include a component that engages the mucosal immune system
against HIV. With this in mind, Dr. Mor?s team at the Arizona State
University, together with Dr. Morgane Bomsel?s laboratory at the Cochin
Institute of Molecular Genetics in Paris, France, created a novel vaccine
candidate.

Our body is delimited to the environment and therefore protected from
outside influences by a layer of different tissues, all summed-up under the
generic name ?epithelia?. Unfortunately, HIV is able to use a feature of
mucosal epithelia, transcytosis, which allows the transport of HIV through
mucosal epithelia. Imagine a soap bubble which transports the virus through
epithelial cells. In fact, transcytosis works pretty much like this.

The process of transcytosis depends on interactions between a viral protein
called gp41 and a specific receptor on the epithelial cell membrane. The
scientists fused the corresponding binding site of gp41 to a subunit of
cholera toxin in order to ensure mucosal targeting and adequate
immunogenicity.

According to the results, published in PNAS, the administration of the
vaccine elicited the mucosal immune system to produce antibodies against the
above mentioned binding-site of gp41 in mice. Furthermore, it was shown,
that those antibodies were effective in preventing transcytosis of HIV-1 ex
vivo. The scientists also demonstrated the possibility of plant production
in Nicotiana benthamiana, which could permit cheap production.

Needle-free delivery is an important feature of this vaccine candidate as
experience has shown that many people in developing countries are very
sceptic of taking medication by injection. The compliance is expected to be
much better, if the medication can be administered orally.

The development of the specific antibody levels suggests that frequent
refreshments of this vaccine candidate may be needed. Although frequent
refreshments would involve quite a logistic effort, plant production and
oral delivery could make vaccination campaigns with multi-component vaccines
feasible one day.

Currently, the scientists are in the middle of pre-clinical testing. The
next big challenge is to show, that the vaccine candidate can protect
non-human primates from infection with a Virus similar to HIV. If all goes
well, the researchers will be able to start phase I/II testing in humans in
about a year, according to Dr. Mor. Those trials have to show the safety and
immunogenicity of the vaccine.

?Only then (based on success in phase I and II) will a third phase trial
commence, in which a large population of volunteers will receive the vaccine
and be monitored for incidence of infection over several years,? said Dr.
Mor. If those trials show satisfactory safety and efficacy, the vaccine
could be approved in five to ten years.

Daniel Schneeberger is a Science Writer for Checkbiotech in Basel,
Switzerland, and is currently studying Medicine at the University of Basel.
Contact him at daniel.schneeberger@stud.unibas.ch.

Matoba N, Magerus A, Geyer BC, Zhang Y, Muralidharan M, Alfsen A, Arntzen
CJ, Bomsel M, Mor TS. Amucosally targeted subunit vaccine candidate
eliciting HIV-1 transcytosis-blocking Abs. Proc Natl Acad Sci 2004 Sep
14;101(37):13584-9.

Abstract available at: www.pnas.org/cgi/content/abstract/101/37/13584

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