1,721,118 research outputs found
Immunogenicity of two recombinant DNA COVID-19 vaccines in young and aged mice
Full text linkBackground: SARS-CoV-2 emerged in December 2019 and spread rapidly around
the world. Vaccination is the most effective way to control the pandemic morbidity
and mortality. While most of the currently available vaccines against COVID-19 have
shown high efficacy against the original strain of SARS-CoV-2, their effectiveness
has declined due to the emergence of new variants and diminished immunity remains
a major threat, especially in older individuals. Therefore, the development of safe and
effective vaccines that can be rapidly adapted to new SARS-CoV-2 variants represents
an urgent health priority. We assessed the immunogenicity of two DNA vaccines
against SARS-CoV-2 variants: pVAX-S1-TM-D614G and pVAX-S1-TM-INDUK.
Methods: pVAX-S1-TM-D614G, encoding the S1 spike subunit in fusion with the
transmembrane region, that allows protein trimerization as predicted by in silico
analysis, was constructed by recombinant DNA technologies; the dominant D614G
substitution was introduced by a PCR-based mutagenesis protocol. pVAX-S1-TM-
INDUK was obtained by the insertion of additional key mutations from Delta (E484Q
and L452R) and Alpha (N501Y and A570D) variants. Antigen expression was verified
in vitro by immunofluorescence assay. To test the immunogenicity of pVAX-S1-TM-
D614G and pVAX-S1-TM-INDUK, they were administered, via intramuscular
injection followed by electroporation, in young and aged mice. The elicited immune
responses were monitored for 6 months.
Results: pVAX-S1-TM-D614G and pVAX-S1-TM-INDUK were first validated in
vitro: a robust expression and membrane localization of antigenic proteins was
demonstrated on transiently transfected HEK-293 cells. Our candidates DNA vaccines
were then tested in vivo in both young (11 weeks of age) and aged (20 months of age)
C57BL/6 mice. When delivered by electroporation, they were able to trigger a
significant anti-SARS-CoV-2 antibody production in immunized mice, although
antibody titer declined 6 months after the second dose, especially in aged animals. Of note, a third booster dose, given at 6 months from the last vaccination, significantly
increased the magnitude of humoral immunity, suggesting that immune recall can
improve antibody durability. Moreover, we optimized a lipid nanoparticle formulation,
we called LNP15, to encapsulate DNA plasmids by microfluidic technology.
Preliminary in vitro and in vivo results obtained with a prototype DNA vaccine,
indicate that LNP15 can successfully encapsulate DNA vaccines for their easier
administration.
Conclusions: We developed two recombinant DNA vaccines (pVAX-S1-TM-D614G
and pVAX-S1-TM-INDUK) against SARS-CoV-2 variants, able to elicit a significant
anti-Spike antibody response in both young and aged mice. Although the humoral
response declined within 6 months, a booster dose can efficiently recall immune
memory and reverse anti-SARS-CoV-2 antibody waning even in aged population.
Moreover, LNP15 formulation might permit to successfully deliver candidate DNA
vaccines by intramuscular injection without electroporation. Given that DNA vaccines
can be easily adapted in response to new variants, are cheaper and more stable than
currently approved vaccines, they represent a promising strategy to achieve global
immunization
The nucleotide sequence of the 5S ribosomal RNA geneof Pyrenophora graminea
Full text linkThe distribution ofthe 5S ribosomal RNA genes in fungi is known
to follow two patterns: either most or all of the 5S genes are
part of the cluster (rDNA) which also encodes the large 17S and
25S ribosomal RNAs, or they are dispersed within the genome,
away from the major rDNA transcript (1, 2). The first pattern
is followed by Hansenula wingei, Kluyveromyces lactis,
Saccharomyces cerevisiae, S. carlsbergensis, S. rosei, Torulopsis
utilis (ascomycetous yeasts), Armillaria mellea, Coprinus
cinereus, Schizophyllum commune, 7hanatephorus praticola
(Basidiomycotina), Mucor racemosus (Zygomycetina) and Achlya
ambisexualis (Oomycetina) whereas the second is followed by
all the filamentous Ascomycotina studied to date (Aspergillus
nidulans, Cochliobolus heterostrophus, Neurospora crassa, as
well as by two ascomycetous yeasts Schizosaccharomyces pombe
and Yarrowia lipolytica). The filamentous ascomycete
Pyrenophora graminea (anamorph: Drechslera graminea) is a
plant pathogen responsible for the leaf stripe disease of barley.
During sequence analysis of a 2.4 kb EcoRI-SmaI fragment, part
of a larger EcoRI genomic clone of the fungus, encompassing
a 0.5 Kb portion of the 25S gene and the intergenic spacer of
the rDNA gene cluster, we have detected a 118 bp long 5S gene
(Figure la) which is located at 0.6 kb from the 3' end of the
25S gene (Figure lb). This finding demonstrates that, in contrast
to what was known till now, both distribution patterns are present
also in the filamentous Ascomycotina
Nucleic acids in mummified plant seeds: biochemistry and molecular genetics of pre-Columbian maize.
No full textPolynucleotide Immunogenic Agents.
No full textPolynucleotide immunogenic agents capable of inducing an immune response towards the members of the epidermal growth factor receptors (EGFR) family are disclose
neu/HER-2 cDNA vaccination and pregnancy loss. DNA Vaccines.
No full textanimal experiment; animal model; animal tissue; conference paper; embryo; embryo resorption; fetus; human; human cell; male; mouse; necrosis; nonhuman; pregnancy disorder; proto oncogene; spontaneous abortion; vaccinatio
DNA codificante forme tronche e chimeriche della proteina p185neu e suoi usi terapeutici
No full textSi descrivono plasmidi contenenti sequenze codificanti diversi frammenti dell’oncoproteina p185neu, in grado di indurre una risposta immunitaria contro tumori esprimenti oncogeni della famiglia ErbB, e loro composizioni farmaceutiche
Plasmids coding for p185neu protein sequence variants and therapeutic uses thereof
No full textThe present invention relates to plasmid vectors containing p185neu - encoding sequences and the use thereof in DNA vaccination against tumours. The plasmids according to the invention contain sequences encoding different fragments of human or rat oncoprotein p185neu and are able to induce a humoral or cell-mediated immune response against tumours expressing oncogenes of the ErbB family.
The invention also relates to pharmaceutical compositions containing said plasmids and their use for the prevention or therapy of p185neu-expressing tumours
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