Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy.

Increased TSPO expression, pyroglutamate-modified amyloid beta (AβN3(pE)) accumulation and transient clustering of microglia in the thalamus of Tg-SwDI mice.

Epidemiological studies showed that Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) frequently co-occur; however, the precise mechanism is not well understood. A unique animal model (Tg-SwDI mice) was developed to investigate the early-onset and robust accumulation of both parenchymal and vascular Aβ in the brain. Tg-SwDI mice have been extensively used to study the mechanisms of cerebrovascular dysfunction, neuroinflammation, neurodegeneration, and cognitive decline observed in AD/CAA patients and to design biomarkers and therapeutic strategies.

An ambient-temperature stable nanoparticle-based vaccine for nasal application that confers long-lasting immunogenicity to carried antigens.

Polyhedrins are viral proteins present in a large family of baculoviruses that form occlusion bodies (polyhedra). These structures protect the virus particles from the outside environment until they are ingested by susceptible insects. Occluded viruses can sustain inclement weather for long periods of time.

Age- and sex-dependent alterations in the peripheral immune system in the 3xTg-AD mouse model of Alzheimer's disease: Increased proportion of CD3+CD4-CD8- double-negative T cells in the blood.

It is well documented that sporadic Alzheimer's disease (AD) is a multifactorial disease and considered to be a result of several pathological events, both in the periphery and in the brain. The role of the peripheral immune system in the etiology and/or progression of the disease is not fully understood yet, and the results in humans are contradictory so far. Several animal models of AD have been generated and thoroughly characterized to elucidate disease mechanisms and evaluate numerous therapeutic strategies in preclinical studies.

Novel monoclonal antibody 3B8 specifically recognizes pyroglutamate-modified amyloid β 3-42 peptide in brain of AD patients and 3xTg-AD transgenic mice.

In addition to the full-length beta-amyloid peptides (Aβ 1-40/42), several Aβ variants, truncated at their N- or C-termini and bearing different post-translational modifications, have been detected in the brain of Alzheimer´s disease (AD) patients. AβN3(pE), an Aβ peptide bearing an amino-terminal pyroglutamate at position 3, is a significant constituent of intracellular, extracellular and vascular Aβ deposits in brain tissue from individuals with AD and Down syndrome. Pioneering immunotherapy studies have primarily focused on the full-length Aβ peptide, disregarding the presence of N-truncated/modified species.

A self-aggregating peptide: implications for the development of thermostable vaccine candidates.

Background: The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines.

Experimental and Theoretical Approaches To Investigate the Immunogenicity of Taenia solium-Derived KE7 Antigen.

cysticercosis, a parasitic disease that affects human health in various regions of the world, is preventable by vaccination. Both the 97-amino-acid-long KETc7 peptide and its carboxyl-terminal, 18-amino-acid-long sequence (GK-1) are found in Both peptides have proven protective capacity against cysticercosis and are part of the highly conserved, cestode-native, 264-amino-acid long protein KE7. KE7 belongs to a ubiquitously distributed family of proteins associated with membrane processes and may participate in several vital cell pathways.

Sodium thiosulphate attenuates brain inflammation induced by systemic lipopolysaccharide administration in C57BL/6J mice.

It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration.

Alpha-mangostin attenuates brain inflammation induced by peripheral lipopolysaccharide administration in C57BL/6J mice.

Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases. Molecules with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated that alpha-mangostin (α-MG), a natural xanthone purified from mangosteen pericarp, reduced brain levels of pro-inflammatory cytokine interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and 18 kDa translocator protein (TSPO) in an animal model of peripheral LPS-induced neuroinflammation.

Variable epitope library carrying heavily mutated survivin-derived CTL epitope variants as a new class of efficient vaccine immunogen tested in a mouse model of breast cancer.

The antigenic variability of tumor cells leading to dynamic changes in cancer epitope landscape along with escape from immune surveillance by down-regulating tumor antigen expression/presentation and immune tolerance are major obstacles for the design of effective vaccines. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response as well as HIV-neutralizing antibodies.

Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain.

The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ deposits in AD and Down syndrome brain tissue. It has been previously demonstrated that rabbits fed a diet enriched in cholesterol and given water containing trace copper levels developed AD-like pathology including intraneuronal and extracellular Aβ accumulation, tau hyperphosphorylation, vascular inflammation, astrocytosis, microgliosis, reduced levels of acetylcholine, as well as learning deficits and thus, may be used as a non-transgenic animal model of sporadic AD.

Anti-11[E]-pyroglutamate-modified amyloid β antibodies cross-react with other pathological Aβ species: relevance for immunotherapy.

N-truncated/modified forms of amyloid beta (Aß) peptide are found in diffused and dense core plaques in Alzheimer's disease (AD) and Down's syndrome patients as well as animal models of AD, and represent highly desirable therapeutic targets. In the present study we have focused on N-truncated/modified Aβ peptide bearing amino-terminal pyroglutamate at position 11 (AβN11(pE)). We identified two B-cell epitopes recognized by rabbit anti-AβN11(pE) polyclonal antibodies.

Inexpensive anti-cysticercosis vaccine: S3Pvac expressed in heat inactivated M13 filamentous phage proves effective against naturally acquired Taenia solium porcine cysticercosis.

In search of reducing vaccine production costs', a recombinant M13 phage version of the anti-cysticercosis tripeptide vaccine (S3Pvac) was developed. The efficacy of S3Pvac-Phage vs. placebo was evaluated in a randomized trial that included 1,047 rural pigs in 16 villages of Central Mexico.

Amyloid-beta peptide binds to microtubule-associated protein 1B (MAP1B).

Extracellular and intraneuronal formation of amyloid-beta aggregates have been demonstrated to be involved in the pathogenesis of Alzheimer's disease. However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of targets have deleterious effects on cellular functions.

A new highly effective anticysticercosis vaccine expressed in transgenic papaya.

The use of transgenic plants as new antigen-delivery systems for subunit vaccines has been increasingly explored. We herein report progress toward a papaya-based vaccine against cysticercosis. Synthetic peptides (KETc1, KETc12, KETc7) were successfully expressed in 19 different transgenic papaya clones and found to be immunogenic.

Improvement of the synthetic tri-peptide vaccine (S3Pvac) against porcine Taenia solium cysticercosis in search of a more effective, inexpensive and manageable vaccine.

Vaccination of pigs may curtail Taenia solium transmission by reducing the number of cysticerci, the precursors of adult intestinal tapeworms in humans. Several antigen preparations induce protection against porcine cysticercosis in experimental settings but only one subunit vaccine (S3Pvac) has been tested and proved effective in the field against naturally acquired disease. Besides improving of the vaccine's effectiveness, significant reductions in production costs and in the logistics of its administration are necessary for the feasibility of nationwide control programs.

Isolation of the Taenia crassiceps antigens from a phage display cDNA library and evaluation of their use for diagnosis of neurocysticercosis.

A novel cDNA cloning strategy consisting in elimination of non-coding DNA sequences from 3' regions of cDNAs was applied to construct the Taenia crassiceps phage displayed cDNA expression library. After biopanning using immune sera, three phage clones expressing T. crassiceps-derived antigens specifically recognizing antibodies present in cerebrospinal fluid and plasma samples from neuroimaging-confirmed neurocysticercosis patients were selected.

Peptide mimotopes of Mycobacterium tuberculosis carbohydrate immunodeterminants.

Cell-surface saccharides of Mycobacterium tuberculosis appear to be crucial factors in tuberculosis pathogenicity and could be useful antigens in tuberculosis immunodiagnosis. In the present study, we report the successful antigenic and immunogenic mimicry of mannose-containing cell-wall compounds of M. tuberculosis by dodecamer peptides identified by phage-display technology.

Mimotopes of conformational epitopes in fibrillar beta-amyloid.

In Alzheimer's disease (AD) beta-amyloid peptide accumulates in the brain in different forms including fibrils. Amyloid fibrils could be recognized as foreign by the mature immune system since they are not present during its development. Thus, using mouse antisera raised against the fibrillar form of Abeta42, we have screened two phage peptide libraries for the presence of foreign conformational mimotopes of Abeta.

Antigenic properties of phage displayed peptides comprising disulfide-bonded loop of the immunodominant region of HIV-1 gp41.

The HIV-1 envelope glycoprotein gp41 contains Cys(X)5Cys motif, which has been shown to elicit a strong antibody response in almost all HIV-1 infected individuals. This disulfide-bonded loop region is conserved in most retroviruses suggesting the existence of an essential function in virus life cycle. In this study, we displayed the peptides comprising 12 amino acids of the immunodominant loop of gp41 on the surface of M13 phage as N-terminal fusions to the minor coat protein pIII and major coat protein pVIII of the phage and demonstrated that cysteine loop containing peptide expressed on phage recognized 62 out of 63 (98.

Recombinant bacteriophage-based multiepitope vaccine against Taenia solium pig cysticercosis.

The aim of this study was to test the capacity of recombinant phages to deliver antigens for vaccination against porcine cysticercosis. Thus, three peptides (KETc1, KETc12, GK1) and a recombinant antigen KETc7, previously proven to induce high levels of protection against pig cysticercosis, were expressed on the surface of the M13 bacteriophage at multiple copies. The pool of these four recombinant phages induced high levels of protection against an experimental murine cysticercosis.

Phage-displayed mimotopes recognizing a biologically active anti-HIV-1 gp120 murine monoclonal antibody.

Antibody-dependent cellular cytotoxicity (ADCC) is a host defense mechanism in which Fc receptor-bearing effector cells in combination with antigen-specific antibodies recognize and kill antigen-expressing target cells. The authors previously described a murine monoclonal antibody (MAb-ID6) that mediated ADCC activity against HIV-infected cells. It was demonstrated that the specificity of MAb-ID6 maps to the first 204 amino acids of gp120; however, the exact epitope was not identified.