scholarly journals Type of RNA Packed in VLPs Impacts IgG Class Switching—Implications for an Influenza Vaccine Design

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 47 ◽  
Author(s):  
Ariane C. Gomes ◽  
E. S. Roesti ◽  
Aadil El-Turabi ◽  
Martin F. Bachmann
Keyword(s):  
Rational Design ◽  
Humoral Response ◽  
Transfer Rna ◽  
Influenza Viruses ◽  
Toll Like Receptor ◽  
M2 Protein ◽  
Cell Responses ◽  
Rule Out ◽  
Inducible Gene

Nucleic acid packed within virus-like particles (VLPs) is shown to shape the immune response and to induce stronger B cell responses in different immunisation models. Here, using a VLP displaying the highly conserved extracellular domain of the M2 protein (M2e) from the influenza viruses as an antigen, we demonstrate that the type of RNA packaged into VLPs can alter the quality of the induced humoral response. By comparing prokaryotic RNA (pRNA), eukaryotic RNA (eRNA) and transfer RNA (tRNA), we find that pRNA induces the most protective IgG subclasses using a murine influenza model. We provide evidence that this process is predominantly dependent on endosomal Toll-like receptor (TLR7), and rule out a role for cytoplasmic mitochondrial antiviral signalling protein (MAVS) and its upstream retinoic acid-inducible gene-I-like receptors (RIG-I). Our findings provide considerations for the rational design of VLP-based vaccines and the immunomodulation exerted by TLR7 ligands packaged within the particles. Based on this work, we conclude that VLPs packing prokaryotic RNA must be preferred whenever a response dominated by IgG2 is desired, while eukaryotic RNA should be employed in order to induce a response dominated by IgG1.

scholarly journals Neuro-COVID long-haulers exhibit broad dysfunction in T cell memory generation and responses to vaccination

2021 ◽  
Author(s):  
Lavanya Visvabharathy ◽  
Barbara Alice Hanson ◽  
Zachary Orban ◽  
Patrick H Lim ◽  
Rishi Jain ◽  
...  
Keyword(s):  
T Cell ◽  
Rational Design ◽  
Predictive Biomarkers ◽  
Health Concern ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
High Prevalence ◽  
Cellular Immune ◽  
Significant Health

The high prevalence of post-acute sequelae of SARS-CoV-2 infection (PASC) is a significant health concern. In particular, virus-specific immunity in patients who suffer from chronic neurologic symptoms after mild acute COVID remain poorly understood. Here, we report that neuro-PASC patients have a specific signature composed of humoral and cellular immune responses that are biased towards different structural proteins compared to healthy COVID convalescents. Interestingly, the severity of cognitive deficits or quality of life markers in neuro-PASC patients are associated with reduced effector molecule expressionn in memory T cells. Furthermore, we demonstrate that T cell responses to SARS-CoV-2 mRNA vaccines are aberrantly elevated in longitudinally sampled neuro-PASC patients compared with healthy COVID convalescents. These data provide a framework for the rational design of diagnostics and predictive biomarkers for long-COVID disease, as well as a blueprint for improved therapeutics.

scholarly journals Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates

2006 ◽  
Vol 203 (5) ◽  
pp. 1249-1258 ◽  
Author(s):  
Ulrike Wille-Reece ◽  
Barbara J. Flynn ◽  
Karin Loré ◽  
Richard A. Koup ◽  
Aaron P. Miles ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Primary Immunization ◽  
Toll Like Receptor ◽  
Gag Protein ◽  
Cell Responses ◽  
Boost Immunization

There is a remarkable heterogeneity in the functional profile (quality) of T cell responses. Importantly, the magnitude and/or quality of a response required for protection may be different depending on the infection. Here, we assessed the capacity of different Toll like receptor (TLR)-binding compounds to influence T helper cell (Th)1 and CD8+ T cell responses when used as adjuvants in nonhuman primates (NHP) with HIV Gag as a model antigen. NHP were immunized with HIV Gag protein emulsified in Montanide ISA 51, an oil-based adjuvant, with or without a TLR7/8 agonist, a TLR8 agonist, or the TLR9 ligand cytosine phosphate guanosine oligodeoxynucleotides (CpG ODN), and boosted 12 wk later with a replication-defective adenovirus-expressing HIV-Gag (rAD-Gag). Animals vaccinated with HIV Gag protein/Montanide and CpG ODN or the TLR7/8 agonist had higher frequencies of Th1 responses after primary immunization compared to all other vaccine groups. Although the rAD-Gag boost did not elevate the frequency of Th1 memory cytokine responses, there was a striking increase in HIV Gag-specific CD8+ T cell responses after the boost in all animals that had received a primary immunization with any of the TLR adjuvants. Importantly, the presence and type of TLR adjuvant used during primary immunization conferred stability and dramatically influenced the magnitude and quality of the Th1 and CD8+ T cell responses after the rAD-Gag boost. These data provide insights for designing prime-boost immunization regimens to optimize Th1 and CD8+ T cell responses.

scholarly journals Creation of a specific and separated pediatric intra-hospital pathway in primary level hospitals during the era of COVID-19

2021 ◽  
Vol 19 ◽  
pp. 205873922110108
Author(s):  
Marco Manfredi ◽  
Pietro Ragni ◽  
Giancarlo Gargano
Keyword(s):  
Quality Of Care ◽  
Severe Acute Respiratory Syndrome ◽  
Healthcare Workers ◽  
Health Agency ◽  
Local Health ◽  
Primary Level ◽  
Level Hospital ◽  
Rule Out

Every new pandemic forces us to start new specific behaviors both in the civil life and within the hospitals trying to contain the spreading of the infection and preserve the more fragile people. In this regard, at the debut of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) pandemic, our Local Health Agency had drastically modified every clinical and organizational pathways in order to limit the diffusion of the infection as well as to maintain a good quality of care and preserve healthcare workers. We report how we have modified the usual pediatric intra-hospital pathways in our primary level hospital to avoid mixing children with suspected and non-suspected symptoms of SARS-CoV-2 infection. Before every hospitalization, regardless of symptoms, each child and him/her parent/caregiver are undergone to rapid antigenic and molecular swab to rule out a SARS-CoV-2 infection; hence, positive patients are transferred to Pediatric Unit of third level hospital equipped by a Pediatric COVID Intensive Unit. We think the healthcare behaviors described in this manuscript can help to reduce the intra-hospital spreading of SARS-CoV-2, although children seem to have a minimal role in the dissemination, but we cannot let down your guard. Simultaneously we observed that the overall children requiring inpatient pediatric evaluation and hospitalization have dramatically decreased from the beginning of pandemic.

scholarly journals Heterologous Humoral Response against H5N1, H7N3, and H9N2 Avian Influenza Viruses after Seasonal Vaccination in a European Elderly Population

Vaccines ◽  
2017 ◽  
Vol 5 (3) ◽  
pp. 17 ◽  
Author(s):  
Ivan Sanz ◽  
Silvia Rojo ◽  
Sonia Tamames ◽  
José Eiros ◽  
Raúl Ortiz de Lejarazu
Keyword(s):  
Avian Influenza ◽  
Elderly Population ◽  
Humoral Response ◽  
Influenza Viruses ◽  
Avian Influenza Viruses

scholarly journals Intergenerational transmission of paternal trauma among US Civil War ex-POWs

2018 ◽  
Vol 115 (44) ◽  
pp. 11215-11220 ◽  
Author(s):  
Dora L. Costa ◽  
Noelle Yetter ◽  
Heather DeSomer
Keyword(s):  
Civil War ◽  
Maternal Nutrition ◽  
Prisoner Of War ◽  
Cultural Effects ◽  
The Us ◽  
Before And After ◽  
In Captivity ◽  
Us Civil War ◽  
Rule Out

We study whether paternal trauma is transmitted to the children of survivors of Confederate prisoner of war (POW) camps during the US Civil War (1861–1865) to affect their longevity at older ages, the mechanisms behind this transmission, and the reversibility of this transmission. We examine children born after the war who survived to age 45, comparing children whose fathers were non-POW veterans and ex-POWs imprisoned in very different camp conditions. We also compare children born before and after the war within the same family by paternal ex-POW status. The sons of ex-POWs imprisoned when camp conditions were at their worst were 1.11 times more likely to die than the sons of non-POWs and 1.09 times more likely to die than the sons of ex-POWs when camp conditions were better. Paternal ex-POW status had no impact on daughters. Among sons born in the fourth quarter, when maternal in utero nutrition was adequate, there was no impact of paternal ex-POW status. In contrast, among sons born in the second quarter, when maternal nutrition was inadequate, the sons of ex-POWs who experienced severe hardship were 1.2 times more likely to die than the sons of non-POWs and ex-POWs who fared better in captivity. Socioeconomic effects, family structure, father-specific survival traits, and maternal effects, including quality of paternal marriages, cannot explain our findings. While we cannot rule out fully psychological or cultural effects, our findings are most consistent with an epigenetic explanation.

scholarly journals Toll-like receptor pre-stimulation protects mice against lethal infection with highly pathogenic influenza viruses

2011 ◽  
Vol 8 (1) ◽  
Author(s):  
Kyoko Shinya ◽  
Tadashi Okamura ◽  
Setsuko Sueta ◽  
Noriyuki Kasai ◽  
Motoko Tanaka ◽  
...  
Keyword(s):  
Influenza Viruses ◽  
Toll Like Receptor ◽  
Highly Pathogenic ◽  
Lethal Infection

scholarly journals Detection of adamantane-sensitive influenza A(H3N2) viruses in Australia, 2017: a cause for hope?

2017 ◽  
Vol 22 (47) ◽  
Author(s):  
Aeron Hurt ◽  
Naomi Komadina ◽  
Yi-Mo Deng ◽  
Matthew Kaye ◽  
Sheena Sullivan ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Season ◽  
Influenza Viruses ◽  
M2 Protein ◽  
H3n2 Influenza

For over a decade virtually all A(H3N2) influenza viruses have been resistant to the adamantane class of antivirals. However, during the 2017 influenza season in Australia, 15/461 (3.3%) adamantane-sensitive A(H3N2) viruses encoding serine at residue 31 of the M2 protein were detected, more than the total number identified globally during the last 6 years. A return to wide circulation of adamantane-sensitive A(H3N2) viruses would revive the option of using these drugs for treatment and prophylaxis.

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