Microalgal emergence is a promising platform with two‐decade historical background for producing vaccines and biopharmaceuticals. During that period, microalgal‐based vaccines have reported ...successful production for various diseases. Thus, species selection is important for genetic transformation and delivery methods that have been developed. Although many vaccine prototypes have been produced for infectious and non‐infectious diseases, fewer studies have reached immunological and immunoprotective evaluations. Microalgae‐made vaccines for Staphylococcus aureus, malaria, influenza, human papilloma, and Zika viruses have been explored in their capacity to induce humoral or cellular immune responses and protective efficacies against experimental challenges. Therefore, specific pathogen antigens and immune system role are important and addressed in controlling these infections. Regarding non‐communicable diseases, these vaccines have been investigated for breast cancer; microalgal‐produced therapeutic molecules and microalgal‐made interferon‐α have been explored for hypertension and potential applications in treating viral infections and cancer, respectively. Thus, conducting immunological trials is emphasized, discussing the promising results observed in terms of immunogenicity, desired immune response for controlling affections, and challenges for achieving the desired protection levels. The potential advantages and hurdles associated with this innovative approach are highlighted, underlining the relevance of assessing immune responses in preclinical and clinical trials to validate the efficacy of these biopharmaceuticals. The promising future of this healthcare technology is also envisaged.
Graphical and Lay Summary
The knowledge of immune responses against infectious and non‐communicable diseases is the basis for the rational design of recombinant vaccines and therapeutic proteins. Microalgae is a recombinant platform for the production, and sometimes delivery, of vaccines and therapeutic proteins. The cumulative evidence of pre‐clinical and clinical studies has demonstrated the protective efficacy of recombinant vaccines and therapeutics to combat infectious and non‐communicable diseases.
Abstract
In recent decades, microalgal biotechnology has become one of the most valuable sources of functional feed additives. Many microalgae, such as
Chlorella
sp.,
Tetraselmis
sp.,
Navicula
sp
.
,
...Phaeodactylum tricornutum
,
Porphyridium cruentum
,
Nannochloropsis gaditana
,
Dunaliella salina
,
Lobosphaera
sp. and
Schizochytrium
sp., have been considered valuable in fish species as they enhance immunostimulant abilities, resistance against infectious diseases and tolerance to environmental stress. For instance, immunological parameters (i.e., respiratory burst activity, phagocytic capacity and IgM production) and immune‐related gene expression (i.e., proinflammatory cytokines) in fish have been manly analysed, demonstrating modulation upon microalgal administration. Moreover, disease resistance to microbial pathogen challenges has also been evidenced in several studies. In this context, the present literature review aims to assemble and reveal published research about the immunostimulant properties of some microalgae and their compounds in the immune systems of farmed fish species, whether model or new, with a high potential for aquaculture. Overall, it remains unclear how microalgae or their bioactive compounds may induce or modulate signals in the immune systems of fish species; however, the inclusion of different microalgal species in fish feed has improved the immune response and increased survival to stress conditions and infectious challenges.
Gastrointestinal infections caused by Clostridium difficile lead to significant impact in terms of morbidity and mortality, causing from mild symptoms, such as a low‐grade fever, watery stools, and ...minor abdominal cramping as well as more severe symptoms such as bloody diarrhea, pseudomembrane colitis, and toxic megacolon. Vaccination is a viable approach to fight against C. difficile and several efforts in this direction are ongoing. Plants are promising vaccine biofactories offering low cost, enhanced safety, and allow for the formulation of oral vaccines. Herein, the CdeM protein, which is a spore antigen associated with immunoprotection against C. difficile, was selected to begin the development of plant‐based vaccine candidates. The vaccine antigen is based in a fusion protein (LTB‐CdeM), carrying the CdeM antigen, fused to the carboxi‐terminus of the B subunit of the Escherichia coli heat‐labile enterotoxin (LTB) as a mucosal immunogenic carrier. LTB‐CdeM was produced in plants using a synthetic optimized gene according codon usage and mRNA stability criteria. The obtained transformed tobacco lines produced the LTB‐CdeM antigen in the range of 52–90 μg/g dry weight leaf tissues. The antigenicity of the plant‐made LTB‐CdeM antigen was evidenced by GM1‐ELISA and immunogenicity assessment performed in test mice revealed that the LTB‐CdeM antigen is orally immunogenic inducing humoral responses against CdeM epitopes. This report constitutes the first step in the development of plant‐based vaccines against C. difficile infection.
Nanovaccines constitute an innovative approach in vaccinology, enabled by the nanotechnology advances on the synthesis, functionalization and application of nanoparticles for immunization. Currently, ...several organic materials such as chitosan, poly(lactic‐co‐glycolic acid), nanopoliplexes and virus‐like particles (VLPs) have been used for nanovaccine development to fight against fish diseases. The oral route is the most practical and economical for fish vaccination; thus, several oral vaccine candidates have been developed by using NPs in which the antigen is encapsulated, surface exposed or recombinantly ensembled (VLPs), leading to promising results in terms of protection capacity against infectious diseases. In this review, the state of the art on oral nanovaccine prototypes developed for use in fish was analysed and discussed. Oral nanovaccines have showed remarkably possibilities for application in fish aquaculture, which surely will be adopted by the industry in the following years.
The use of recombinant algae for the production of valuable compounds is opening promising biotechnological applications. However, the development of efficient expression approaches is still needed ...to expand the exploitation of microalgae in biotechnology. Herein, the concept of using viral expression vectors in microalgae was explored for the first time. An inducible geminiviral vector leading to Rep-mediated replication of the expression cassette allowed the production of antigenic proteins at high levels. This system, called Algevir, allows the production of complex viral proteins (GP1 from
) and bacterial toxin subunits (B subunit of the heat-labile
enterotoxin), which retained their antigenic activity. The highest achieved yield was 1.25 mg/g fresh biomass (6 mg/L of culture), which was attained 3 days after transformation. The Algevir system allows for a fast and efficient production of recombinant proteins, overcoming the difficulties imposed by the low yields and unstable expression patterns frequently observed in stably transformed microalgae at the nuclear level; as well as the toxicity of some target proteins.
Vaccines for human use have conventionally been developed by the production of (1) microbial pathogens in eggs or mammalian cells that are then inactivated, or (2) by the production of pathogen ...proteins in mammalian and insect cells that are purified for vaccine formulation, as well as, more recently, (3) by using RNA or DNA fragments from pathogens. Another approach for recombinant antigen production in the last three decades has been the use of plants as biofactories. Only have few plant-produced vaccines been evaluated in clinical trials to fight against diseases, of which COVID-19 vaccines are the most recent to be FDA approved. In silico tools have accelerated vaccine design, which, combined with transitory antigen expression in plants, has led to the testing of promising prototypes in pre-clinical and clinical trials. Therefore, this review deals with a description of immunoinformatic tools and plant genetic engineering technologies used for antigen design (virus-like particles (VLP), subunit vaccines, VLP chimeras) and the main strategies for high antigen production levels. These key topics for plant-made vaccine development are discussed and perspectives are provided.
Objective To evaluate whether a coupled family history of diabetes (FHD) and low birth weight (LBW) or high birth weight (HBW) is associated with metabolic syndrome (MetS) in children and ...adolescents. Study design A total of 1262 children and adolescents age 7-15 years were randomly selected to enroll in this cross-sectional, community-based study. Results In the overall population, HBW (odds ratio OR = 1.4; 95% confidence interval CI = 1.2-10.9), but not LBW (OR = 0.97; 95% CI = 0.6-2.1), was significantly associated with MetS. In the group without FHD, HBW (OR = 1.730; 95% CI = 1.1-2.7), but not LBW (OR = 1.139; 95% CI = 0.7-23), was associated with MetS. In the group with FHD, both LBW (OR = 2.690; 95% CI = 1.4-15.1) and HBW (OR = 3.289; 95% CI = 1.3-30.6) were associated with MetS. Both LBW (OR = 4.710; 95% CI = 1.4-39.7) and HBW (OR = 3.127; 95% CI = 1.3-45.1) were associated with MetS in children and adolescents with FHD in the maternal branch but not in the paternal branch. Conclusions HBW or LBW, in combination with positive FHD in the maternal branch, are determinants of MetS.
Since the tau protein is closely involved in the physiopathology of Alzheimer's disease (AD), studying its behavior in cellular models might lead to new insights on understanding this devastating ...disease at molecular levels. In the present study, primary cultures of human fibroblasts were established and used to determine the expression and localization of the tau protein in distinct phosphorylation states in both untransfected and tau gene-transfected cells subjected to oxidative stress. Higher immunopositivity to phospho-tau was observed in cell nuclei in response to oxidative stress, while the levels of total tau in the cytosol remained unchanged. These findings were observed in both untransfected cells and those transfected with the tau gene. The present work represents a useful model for studying the physiopathology of AD at the cellular level in terms of tau protein implications.
Rodríguez‐Moran M, Guerrero‐Romero F, Aradillas‐García R, Simental‐Mendia LE, Monreal‐Escalante E, de la Cruz Mendoza E. Obesity and family history of diabetes as risk factors of impaired fasting ...glucose: implications for the early detection of prediabetes.
Objective: To determine whether the association between family history of diabetes (FHD) and impaired fasting glucose (IFG) is independent of body mass index (BMI) in children and adolescents.
Methods: In all 443 (11.9%) children and adolescents with FHD, and 3280 (88.1%) without FHD were enrolled in a population‐based cross‐sectional study. Eligible subjects to participate were apparently healthy children and adolescents aged 7–15 yr from Middle and Northern Mexico. Obesity was defined by age‐ and gender‐specific BMI ≥ 95th percentile. FHD was defined as positive if at least one first degree relative had diabetes. The IFG was defined by fasting plasma glucose ≥ 100 mg/dL and < 126 mg/dL.
Results: IFG was identified in 390 (88.0%) and 62 (1.9%) children and adolescents with and without FHD, respectively. In the group with positive FHD, IFG was diagnosed in 146 (37.4%), 79 (20.2%), and 165 (42.3%) children and adolescents who were obese, overweight, and normal‐weight, respectively. On the other hand, in the group without FHD, IFG was identified in 21 (33.9%), 14 (22.6%), and 27 (43.5%) children and adolescents who were obese, overweight, and normal‐weight, respectively. In the overall population, the age‐, sex‐, and BMI‐adjusted logistic regression analysis showed a strong and independent association between FHD and IFG odds ratio (OR) −11.7; 95% CI 9.5–21.2. This association remained strong for girls and boys in a subsequent analysis stratified for BMI category.
Conclusions: The presence of FHD in a first degree relative is associated with IFG, even in the absence of obesity.
The development of new alternative platforms for subunit vaccine production is a priority in the biomedical field. In this study, Ustilago maydis, the causal agent of common corn smut or ...'huitlacoche'has been genetically engineered to assess expression and immunogenicity of the B subunit of the cholera toxin (CTB), a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight (0.8% of the total soluble protein). Mice orally immunized with 'huitlacoche'-derived CTB showed significant humoral responses that were well-correlated with protection against challenge with the cholera toxin (CT). These findings demonstrate the feasibility of using edible corn smut as a safe, effective, and low-cost platform for production and delivery of a subunit oral vaccine. The implications of this platform in the area of molecular pharming are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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