. Author manuscript; available in PMC: 2016 Oct 1.

Published in final edited form as: Trends Plant Sci. 2015 Oct;20(10):622–640. doi: 10.1016/j.tplants.2015.07.004

Table 3.

Chloroplast bioreactors for functional biopharmaceuticals and vaccine antigens

Biophamarceuticals Vaccine antigens	Expression system	Expression level	Functional evaluation	Refs
CTB-AMA1 (Malarial vaccine antigens apical membrane antigen-1 )	Lettuce	7.3% TSP	Dual immunity against two major infectious diseases -cholera and malaria for long-term	[78]
	Tobacco	13.2 % TSP		[78]
CTB-MSP1(Malarial vaccine antigens merozoite surface protein-1)	Lettuce	6.1% TSP	Dual immunity against two major infectious diseases-cholera and malaria for long-term	[78]
	Tobacco	10.1 TSP
EDA (Extra domain A-fibronectin)	Tobacco	2.0 % TSP	Retains the proinfammatory properties of the EDA produced in E. coli	[100]
2 L21-TD	Tobacco	6% TSP	Immunogenic response in mice.	[101]
The immunogenic fusion protein F1-V from Y. pestis	Lettuce	0.08% TSP	Immunogenic response in mice.	[79]
Coagulation factor IX	Tobacco	3.8 % TSP	Prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice	[75]
BACE ( human β-site APP cleaving enzyme)	Tobacco	2.0% TSP	Immunogenic response against the BACE antigen in mice.	[102]
Human papillomavirus L1 protein	Tobacco	21.5 % TSP	Confirmed the formation of capsomeres	[103]
Proinsulin	Tobacco	47% TSP	Oral delivery of proinsulin in plant cells or injectable delivery into mice showed reduced blood glucose levels	[70]
PA(dIV) (Domain IV of Bacillus anthracis protective antigen)	Tobacco	5.3% TSP	Demonstrates protective immunity in mice against anthrax	[104]
Human thioredoxin 1 protein	Lettuce	1% TSP	Protected mouse insulinoma line 6 cells from hydrogen peroxide	[105]
Thioredoxins–human serum albumin fusions	Tobacco	26% TSP	The in vitro chaperone activity of Trx m and f was demonstrated	[106]
HPV-16 L1 antigen fused with LTB	Tobacco	2% TSP	Proper folding and display of conformational epitopes	[107]
Exendin-4 (EX4) fused to CTB	Tobacco	14.3 % TSP	CTBEX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6.	[66]
CTB-ESAT-6 (6kDa early secretory antigenic target)	Tobacco	up to 7.5%;	Hemolysis assay and GM1-binding assay confirmed functionality and structure of the ESAT-6 antigen	[80]
CTB-ESAT-6 (6kDa early secretory antigenic target)	Lettuce	0.75%		[80]
CTB-Mtb72F (a fusion polyprotein from two Tuberculosis antigens, Mtb32 and 39)	Tobacco	up to 1.2 %	Not reported
CTB fused with MBP (myelin basic protein)			Amyloid loads were reduced in vivo in brain regions of 3xTgAD mice fed with bioencapsulated CTB-MBP. Also reduced A beta(42) accumulation in retinae and prevented loss of retinal ganglion cells were observed in 3xTgAD mice treated with CTB-MBP.	[65]
Coagulation factor VIII (FVIII) antigens: heavy chain (HC) and C2 fused with CTB	Tobacco	80 or 370 μg/g in fresh leaves	Feeding of HC/C2 mixture substantially suppressed T helper cell responses and inhibitor formation against FVIII in hemophilia A mice.	[77]