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The current pandemic called COVID-19 caused by the SARS-CoV-2 virus brought the need for the search for fast alternatives to both control and fight the SARS-CoV-2 infection. Therefore, a race for a vaccine against COVID-19 took place, and some vaccines have been approved for emergency use in several countries in a record time. Ongoing prophylactic research has sought faster, safer, and precise alternatives by redirecting knowledge of other vaccines, and/or the development of new strategies using available tools, mainly in the areas of genomics and bioinformatics. The current review highlights the development of synthetic antigen vaccines, focusing on the usage of bioinformatics tools for the selection and construction of antigens on the different vaccine constructions under development, as well as strategies to optimize vaccines for COVID-19.

Escherichia coli O157:H7 is considered as emerging foodborne pathogens that occur globally. Three major virulence protein factors; EspA(E), intimin(I), Tir(T) and Stx2 toxin have been found to be highly associated with bloody diarrhoea or, Haemolytic Uremic Syndrome. In this study, a trivalent recombinant EIT in combination with the binding domain of STX toxin were encapsulated with chitosan nanoparticles as a combination vaccine candidate. Mice were immunized either subcutaneously or orally with these antigens and challenged with E. coli O157:H7. Results of the binding inhibition assay with caco2 cell monolayer show a significant reduction in the adhesion percentage of pre-treated E. coli O157:H7 with immunized mice sera. Evaluation of neutralizing abilities of immune sera pre-incubated with CD50 dose of STX2 by Vero cells cytotoxicity neutralization assay shows less morphological reforms in comparison with the control groups. Results of mice mortality challenge with STX2 demonstrate around 66% of survived in immunized mice. In a challenge experiment with E. coli O157:H7, all the immunized mice showed a significant decrease in bacterial colonization and shedding. The results indicate that the use of multiple recombinant proteins in combination with natural nanostructure effectively evocated strong humoral and mucosal response, increasing the protection capacity of the synthetic antigen.

Mycobacterium tuberculosis infects one third of the world's population. Due to variable efficacy of the Bacille Calmette Guerin (BCG) vaccine, development of novel TB vaccines remains a priority. Here, we demonstrate the protective efficacy of a novel multivalent DNA vaccine, which contains 15 synthetic antigens targeting the Mtb ESX secretion system.

Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions.

Hexoestrol and its derivatives, hexoestrol-mono-ether-butyrate-ethyl (HES-MEBE), hexoestrol-di-ether-butyrate-ethyl (HES-DEBE) were separated and identified using liquid chromatography and spectrometry (ESI). The conditions were as follows: Methyl alcohol and water as mobile phase, 0.3 ml/min of flow rate, elution with linear gradient concentrations from 60–100% of methanol for 25 min on a Lichrospher C-18 column. Synthetic antigen was prepared by coupling hexoestrol-mono-caroxyl-propyl-ethyl (HES-MCPE) with carrier protein by the mixed anhydride method, and the conjugation rate, analysed by UV scanning, is 36.

A synthetic multistage, multi-epitope Plasmodium falciparum malaria antigen (FALVAC-1A) was designed and evaluated in silico, and then the gene was constructed and expressed in Escherichia coli. The FALVAC-1A protein was purified by inclusion body isolation, followed by affinity and ion exchange chromatography. Although FALVAC-1A was a synthetic antigen, it folded to a specific, but as yet incompletely defined, molecular conformation that was stable and comparable from lot to lot. When formulated with four different adjuvants, FALVAC-1A was highly immunogenic in rabbits, inducing not only ELISA reactivity to the cognate antigen and most of its component epitopes, but also in vitro activity against P. falciparum parasites as demonstrated by inhibition of sporozoite invasion, antibody dependent cellular inhibition and the immunofluorescence assay.

4-Nitrophenyl 2,3-O-isopropylidine-α-D-mannopyranoside 2 was condensed with O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-(1→2)-3,4,6-tri-O-acetyl-α-D-mannopyranosyl bromide 1 and 2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl bromide 11 in the presence of mercuric cyanide. Products were deprotected to yield, respectively, 4-nitrophenyl O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 6 and 4-nitrophenyl O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 14. The 4-nitrophenyl group of 6 was reduced to give title trisaccharide. Bromide 1 was also condensed with methyl 2,3,4-tri-O-benzyl-α-D-manopyranoside 3 in the presence of silver trifluoromethanesulfonate and tetramethylurea to give protected trisaccharide derivative which was deprotected to furnish, methyl O-α-D-mannopyranosyl-(1→2)-O-α-D-mannopyranosyl-(1→6)-α-D-mannopyranoside 10. The identities of all protected and deprotected compounds were supported by 1H and 13C NMR spectral data.

Since the idiosyncratic liver toxicity of methyl dopa (L-alpha-methyl-3,4- dihydroxy-phenylalanine) may be due to immune mediated mechanisms, immunologic tools are needed to detect methyl dopa induced antibody and antigen. Hapten (methyl dopa)--carrier (albumin) conjugates were synthesized to generate antibodies reactive with this drug. Studies were also conducted to test the immunogenicity of this hapten-carrier conjugate and its cross reactivity with methyl catechol and levodopa. Methyl dopa (MD), levodopa (LD) or methyl catechol (MC) were conjugated to rabbit serum albumin (RSA) under high pH (base) conditions or by a tyrosinase (tyr) catalyzed reaction. Under the base conjugation conditions, MD-RSA, LD-RSA and MC-RSA conjugates were produced at higher hapten: carrier ratios than conjugates produced by the enzyme catalyzed reaction. Rabbits were subsequently immunized with either MD-RSA(base) or MD-RSA(tyr). Antibodies elicited by MD-RSA(base) had marked reactivity to the carrier protein, albumin, whereas antibodies elicited by MD-RSA(tyr) did not. In addition, reactivity of anti-MD antibody was equal to or greater with MC-RSA than reactivity with either MD-RSA or LD-RSA. This work suggests that the conjugation method using the tyr catalyzed reaction produces the optimal immunogen with minimal modification of the carrier protein. In addition, the catechol moiety of MD, MC and LD appears to be the immunogenic epitope on these haptens.

The para-aminophenyl derivative of Manα1→2Manα1→6Manα1→ was coupled via a diazotization reaction to bovine serum albumin, and the resulting glycoconjugate was used to immunize two rabbits. The resultant antisera were tested for reactivity with a number of related mono, di- and trisaccharides to determine the immunodominant portion of this trisaccharide. Two populations of antibody resulted, one of which required the reducing end mannose, and could react with either an N-acetylglucosamine or a mannose as the penultimate sugar. The other population reacted with the Manα1→2Manα1→6Manα1→. The aglycone moiety and its configurations play an important role in determining the specificity of antibodies to this synthetic antigen. The similarity of this reactivity to the reactivity of mannose binding lectins is discussed.

Antibody to chemically synthesized Fuc alpha 1----3 Gal-1----OC6H4N = N bovine serum albumin was developed. Specificity analysis using related synthetic saccharides was performed. The antisera were shown to be specific for both sugars in the disaccharide, to the 1----3 positional linkage and to the alpha anomeric configuration. Immunohistochemical staining was performed on benign disease and adenocarcinoma tissue of the colon. 5/8 of the benign colon polyp tissue and 4/6 of the colonic adenocarcinoma tissue showed strong granular cytoplasmic staining of the epithelia cells lining the ducts. None of the six normal colon tissues tested showed any reactivity. Immunohistochemical staining was also performed on tissue from benign disease and from carcinoma of the mammary gland. 2/5 of the tissue from benign disease of the breast and 3/6 of the tissue from breast carcinoma showed strong granular cytoplasmic staining of the ductal epithelial cells.

SummaryThe use of the C-peptide radioimmunoassay has become possible due to the availability of synthetic antigen and improvement in antisera production.Proinsulin cross-reactivity can be avoided and C-peptide specifically determined by extraction of proinsulin with sepharose-bound insulin antibodies. In insulin treated diabetics, proinsulin insulin antibody complexes can be precipitated with polyethylene glycol (PEG) or concentrated ethanol. C-peptide immunoassay is leasable even in presence of exogenous insulin.With this assay it has been shown that1) almost half of the growth-onset diabetics have a residual insulin secretion, 2) residual β-ceil activity is associated with a better diabetic control and 3) perhaps a lesser degree of degenerative complications.Finally, hypoglycemic conditions can be better documented by simultaneous determination of Cpeptide and insulin in blood.