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Edible Algae Vaccines
Edible algae based vaccination is a developing vaccination strategy that usually combines a genetically engineering sub-unit vaccine and an immunologic adjuvant into C. reinhardtii micro algae. Micro algae can then be freeze dried and administered orally. While previous plant based vaccines have been approved for market production in the past, all current edible algal vaccines still reside in pre-clinical trials. Due to the relatively low production cost of algal growth, the completion of a market ready edible algae vaccine would have a profound impact in the administration and distribution of immunizations in impoverished populations.

History
In 2003, the first documented algal-based vaccine antigen was reported, comprised of a foot-and-mouth disease antigen complexed with the cholera toxin subunit B which delivered the antigen to digestion mucosal surfaces in mice. The vaccine was grown in C. reinhardtii algae and provided oral vaccination in mice but was hindered by low vaccine antigen expression levels (Sun et al)

In 2007, a classical swine fever virus (CSFV) was produced in C. reinhardtii, that providing immunity in mice that were subcutaneously administered (injected) the vaccine but lacked oral immunization. No adjuvant(delivery mechanism)was provided in orally vaccinated mice. (He et al., 2007)

Further studies have been conducted in C. reinhardtii and have depended heavily upon antigen expression yields, antibody titers elicited from the antigen and the adjuvent(delivery system) that the vaccine was administered with.

Pre-clinical trials in mice involving an edible algae based malaria vaccine were successful in a limited capacity in 2012. Using an edible algae produced fusion protein of the malaria membrane protein pfs25 and the ganglioside binding protein ctxB, researchers were able to induce production of IgA antibodies in mice. IgA antibodies commonly reside in mucosal linings which coincides with the site of vaccine delivery. However, a significant production of IgG antibodies, which are the most common antibodies in circulation, was not found in mice that were only immunized solely via the edible algae vaccine.

Challenges Algae Overcomes as an Expression Platform
Algae as an expression system overcomes several challenges other recombination vectors suffer from.

The production of therapeutic proteins, including vaccines, often requires costly purification steps. Recombination proteins produced by genetically engineered algae have accounted for up to 5.0% of all protein produced by the algae, enough to have a significant impact when ingested by mice. The elimination of a purification procedure reduces the total cost of a recombination edible vaccine significantly.

Furthermore, algae as a plant microorganism is also relatively inexpensive to produce. Modern cultivation techniques currently generate algae at a rate of 3$/kilogram.

Proteins expressed inside the chloroplast of algae (the most common site of genetic engineering and protein production) do not undergo glycosylation, a form of posttranslational modification. Glycosylation of proteins that are not naturally modified like the malaria vaccine candidate pfs25 can occur in common expression systems like yeast. Algae provides a glycosylation free environment, helping ensure proteins like malaria vaccine candidate pfs25 retain their natural, unmodified structure.

List of Algal-produced Vaccines in Pre-clinical Studies

 * Foot-and-mouth disease
 * Hepatitis B
 * Classical swine fever virus
 * White spot syndrome virus
 * Staphylococcus aureus (common cause of boils, sinusitis)
 * Malaria
 * HPV

The Future of Edible Algal Vaccines
Algae stands as a strong, high throughput expression platform, capable of producing and folding many recombinant therapeutic proteins. Currently, cholera toxin sub-unit B stands as the most serviceable adjuvant (delivery mechanism), however the development of a stronger binding, immune-response-inducing protein or particle is actively under development. The convenience and speed of algal growth provides a more efficient means of testing new vaccine protein delivery mechanisms.

Algae based vaccines, while relatively inexpensive, will likely not replace vaccination strategies for diseases that are currently managed by existing vaccines, however algae may act as a useful platform for novel vaccines or replacing extremely expensive vaccines for viruses like HPV.