Mosaic neuraminidase-based vaccine induces antigen-specific T cell responses against homologous and heterologous influenza viruses.

Seasonal influenza is an annually severe crisis for global public health, and an ideal influenza vaccine is expected to provide broad protection against constantly drifted strains. Compared to highly flexible hemagglutinin (HA), increasing data have demonstrated that neuraminidase (NA) might be a potential target against influenza variants. In the present study, a series of genetic algorithm-based mosaic NA were designed, and then cloned into recombinant DNA and replication-defective Vesicular Stomatitis Virus (VSV) vector as a novel influenza vaccine candidate.

A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice.

Background: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines.

Methods: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4 T cells, and 11 CD8 T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice.

Rapid Induction of Long-Lasting Systemic and Mucosal Immunity via Thermostable Microneedle-Mediated Chitosan Oligosaccharide-Encapsulated DNA Nanoparticles.

Most existing vaccines, delivered by intramuscular injection (IM), are typically associated with stringent storage requirements under cold-chain distribution and professional administration by medical personnel and often result in the induction of weak mucosal immunity. In this context, we reported a microneedle (MN) patch to deliver chitosan oligosaccharide (COS)-encapsulated DNA vaccines (DNA@COS) encoding spike and nucleocapsid proteins of SARS-CoV-2 as a vaccination technology. Compared with IM immunization, intradermal administration via the MN-mediated DNA vaccine effectively induces a comparable level of neutralizing antibody against SARS-CoV-2 variants.

Effect of seasonal coronavirus immune imprinting on the immunogenicity of inactivated COVID-19 vaccination.

Background: Pre-existing cross-reactive immunity among different coronaviruses, also termed immune imprinting, may have a comprehensive impact on subsequent SARS-CoV-2 infection and COVID-19 vaccination effectiveness. Here, we aim to explore the interplay between pre-existing seasonal coronaviruses (sCoVs) antibodies and the humoral immunity induced by COVID-19 vaccination.

Methods: We first collected serum samples from healthy donors prior to COVID-19 pandemic and individuals who had received COVID-19 vaccination post-pandemic in China, and the levels of IgG antibodies against sCoVs and SARS-CoV-2 were detected by ELISA.

Enhancement of SARS-CoV-2 N Antigen-Specific T Cell Functionality by Modulating the Autophagy-Mediated Signal Pathway in Mice.

The frequent SARS-CoV-2 variants have caused a continual challenge, weakening the effectiveness of current vaccines, and thus it is of great importance to induce robust and conserved T cellular immunity for developing the next-generation vaccine against SARS-CoV-2 variants. In this study, we proposed a conception of enhancing the SARS-CoV-2 specific T cell functionality by fusing autophagosome-associated LC3b protein to the nucleocapsid (N) (N-LC3b). When compared to N protein alone, the N-LC3b protein was more effectively targeted to the autophagosome/lysosome/MHC II compartment signal pathway and thus elicited stronger CD4 and CD8 T cell immune responses in mice.

A recombinant -based surface display system for developing the T cell-based COVID-19 vaccine.

The immune escape mutations of SARS-CoV-2 variants emerged frequently, posing a new challenge to weaken the protective efficacy of current vaccines. Thus, the development of novel SARS-CoV-2 vaccines is of great significance for future epidemic prevention and control. We herein reported constructing the attenuated () as a bacterial surface display system to carry the spike (S) and nucleocapsid (N) of SARS-CoV-2.

Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/ IRF3-mediated IFN-β production.

Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases. However, its role in host-pathogen interactions has not been characterized yet. Herein, we identified that kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the KP, and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerted a novel antiviral function against a broad range of viruses.

Exacerbated AIDS Progression by PD-1 Blockade during Therapeutic Vaccination in Chronically Simian Immunodeficiency Virus-Infected Rhesus Macaques after Interruption of Antiretroviral Therapy.

The persistence of cells latently infected with HIV-1, named the latent reservoir, is the major barrier to HIV-1 eradication, and the formation and maintenance of the latent reservoir might be exacerbated by activation of the immunoinhibitory pathway and dysfunction of CD8 T cells during HIV-1 infection. Our previous findings demonstrated that prophylactic vaccination combined with PD-1 blockade generated distinct immune response profiles and conferred effective control of highly pathogenic SIV infection in rhesus macaques. However, to our surprise, herein we found that a therapeutic vaccination in combination with PD-1 blockade resulted in activation of the viral reservoir, faster viral rebound after treatment interruption, accelerated AIDS progression, and, ultimately, death in chronically SIV-infected macaques after antiretroviral therapy (ART) interruption.

A calmodulin targeted by miRNA scaffold659_26519 regulates IL-17 expression in the early immune response of oyster Crassostrea gigas.

Calmodulin (CaM) is a highly conserved second messenger protein transducing calcium signals by binding and modulating intracellular calcium ions (Ca), and involves in the Ca-dependent physical processes including host defense in vertebrates. In the present study, a CaM homologue (designated as CgCaM) was identified from Pacific oyster Crassostrea gigas. The open reading frame of CgCaM cDNA was of 471 bp encoding a polypeptide of 156 amino acid residues.

An activating transcription factor 6 beta (ATF6β) regulates apoptosis of hemocyte during immune response in Crassostrea gigas.

The homeostasis of immune cells during immune response is vital for hosts to defend against invaders. Activating transcription factor 6 (ATF6) is an important transcription factor in the unfolded protein response (UPR) to maintaining cellular homeostasis. In the present study, one ATF6 homologue was identified from Pacific oyster Crassostrea gigas (designated as CgATF6β).

The Dicer from oyster Crassostrea gigas functions as an intracellular recognition molecule and effector in anti-viral immunity.

Dicer, as a member of ribonuclease III family, functions in RNA interference (RNAi) pathway to direct sequence-specific degradation of cognate mRNA. It plays important roles in antiviral immunity and production of microRNAs. In the present study, a Dicer gene was identified from oyster Crassostrea gigas, and its open reading frame (ORF) encoded a polypeptide (designed as CgDicer) of 1873 amino acids containing two conserved ribonuclease III domains (RIBOc) and a double-stranded RNA-binding motif (DSRM).

CgSOCS6 negatively regulates the expression of CgIL17s and CgDefh1 in the pacific oyster Crassostrea gigas.

As a family of negatively feedback regulating factors, the suppressor of cytokine signaling (SOCS) can depress cytokine signal transduction, and eventually modulate growth, development, differentiation, and immune response. In the present study, a SOCS homologue (designated as CgSOCS6) was identified from oyster Crassostrea gigas. The open reading frame of CgSOCS6 cDNA was of 1167 bp encoding a peptide of 388 amino acid residues with a central Src homology 2 (SH2) domain, a conserved C-terminal SOCS box, and a nucleus localization sequence (NLS) in its N-terminus.

ATG10 (autophagy-related 10) regulates the formation of autophagosome in the anti-virus immune response of pacific oyster (Crassostrea gigas).

Autophagy, a highly conserved intracellular degradation system, is involved in numerous processes in vertebrate and invertebrate, such as cell survival, ageing, and immune responses. However, the detailed molecular mechanism of autophagy and its immune regulatory role in bivalves are still not well understood. In the present study, an autophagy-related protein ATG10 (designated as CgATG10) was identified from Pacific oyster Crassostrea gigas.

The lectin domain containing proteins with mucosal immunity and digestive functions in oyster Crassostrea gigas.

Lectins are carbohydrate-binding proteins with lectin domains, which are extensively studied for their numerous roles in biological recognition. However, the lectin domain containing proteins (LDCPs) chimerized with other non-lectin domains have not received sufficient attention. In the present study, a genome-wide survey of LDCPs in oyster Crassostrea gigas was conducted, and an expansive 640 LDCPs derived from ten lectin domains were identified and functionally explored.

A novel globular C1q domain containing protein (C1qDC-7) from Crassostrea gigas acts as pattern recognition receptor with broad recognition spectrum.

The globular C1q domain containing (C1qDC) proteins are a family of versatile pattern recognition receptors (PRRs) to bind various ligands by their globular C1q (gC1q) domain. In the present study, a novel globular C1qDC (CgC1qDC-7) was characterized from Pacific oyster Crassostrea gigas. The open reading frame of CgC1qDC-7 was of 555 bp, encoding a polypeptide of 185 amino acids.