A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants
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ABSTRACT:
ORGANISM(S): Mesocricetus auratus
PROVIDER: GSE200596 | GEO | 2022/05/16
REPOSITORIES: GEO
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Project description:Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.
| S-EPMC10159847 | biostudies-literature
Project description:Using microarray analyses and subsequent verification by RT-PCR, we studied the changes in gene expression in the inferior colliculus after an ictal event in one models of audiogenic epilepsy, genetic audiogenic seizure hamster (GASH:Sal). GASH:Sal, a hamster strain developed at the University of Salamanca, exhibits genetic audiogenic epilepsy similar to human Grand Mal epilepsy. GASH:Sal shows an autosomal recessive inheritance for susceptibility to audiogenic seizures, which manifest more severely in young animals; the seizure severity progressively declines with age. Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were subjected to auditory stimulation, and 60 minutes after stimulation, the inferior colliculi were collected. As a control, intact Wistar rats and Syrian hamsters were subjected to identical stimulation and tissue preparation protocols to those performed on the experimental animals. A total of 24 animals were used in this study according to the following distribution: 12 control Syrian hamsters (Mesocricetus auratus) and 12 GASH:Sal at 16 weeks of age and a body weight of approximately 60 g. Six animals Syrian and GASH:Sal hamsters, respectively, were exposed to auditory stimulation, and 60 min after the seizures, we harvested the IC for all gene expression analyses (stimulated Syrian hamsters and stimulated GASH:Sal hamsters). As controls, other six animals Syrian and GASH:Sal hamsters, respectively, were not exposed to the same stimulation (Syrian hamsters and GASH:Sal hamsters).
2015-12-31 | E-GEOD-74043 | biostudies-arrayexpress
Project description:Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens1. Live attenuated influenza vaccine (LAIV) is commonly used in children2, but its effectiveness declines with age3. This may be attributed to the gradual accumulation of homo- or hetero-subtypic immunity that blocks vaccine replication necessary to induce protective responses3, 4. Despite its demonstrable efficacy against influenza in children, correlates of protection for LAIV remain elusive5. Studying young adult volunteers we found that LAIV induced distinct, compartmentalized, antibody responses in the mucosa and blood. LAIV also induced mucosal IL-33 release in the first 8 hours post-inoculation and distinct CD8+ and cTfh T cell activation profiles. Mucosal antibodies are induced separately from blood antibodies and may provide a simple and novel correlate of protection for mucosal vaccination.
2023-10-19 | GSE230494 | GEO
Project description:A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants
| PRJNA825496 | ENA
Project description:Very few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are currently in pre-clinical or clinical development. We rationally attenuated SARS-CoV-2 (isolate WA1/2020) by removing the polybasic cleavage site within the spike protein and the open reading frames (ORFs) 6-8, and by introducing a pair of mutations into the non-structural protein 1 (Nsp1). The derived virus (WA1-DPRRA-ORF6-8-Nsp1K164A/H165A) became severely attenuated in both the K18-human ACE2 (hACE2) transgenic mice and in Syrian hamsters. Transcriptomic profiling of nasal turbinates and lung tissues of infected Syrian hamsters confirmed that WA1-DPRRA-ORF6-8-Nsp1K164A/H165A attenuated the upregulation of proinflammatory pathways. A single intranasal immunization of just 100 PFU of the WA1-DPRRA-ORF6-8-Nsp1K164A/H165A elicited binding and neutralizing antibody responses in Syrian hamsters and completely protected against SARS-CoV-2-induced weight loss and pneumonia. These data demonstrate the feasibility of rational attenuation of SARS-CoV-2. WA1-DPRRA-ORF6-8-Nsp1K164A/H165A represents a promising live attenuated vaccine candidate.
2022-04-04 | GSE199922 | GEO
Project description:BackgroundInfluenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established.MethodsSeventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses.ResultsOnly 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination.ConclusionsProtection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.
| S-EPMC3571238 | biostudies-literature
Project description:Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to influenza vaccination is not yet fully understood. In this study, we inoculated healthy adults with live Streptococcus pneumoniae and vaccinated them 3 days later with either tetravalent-inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). Vaccine-induced immune responses were assessed in nose, blood, and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, experimentally induced pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared with either the TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. Therefore, nasopharyngeal pneumococcal colonization may affect LAIV efficacy.
| S-EPMC7934923 | biostudies-literature
Project description:Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8+ and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.
| S-EPMC10697962 | biostudies-literature
Project description:1. The experiment was performed to assess if the newly discovered Syrian hamster specific anti-PD-L1 antibody could induce a biologically relevant change in transcriptome profile in the tumours. This would confirm that the antibody has functional properties. In the larger picture, the Syrian Hamster model is favored over the mouse model for the development of vaccines and testing of oncolytic viruses/immunotherapies. This is because the model is semi permissive to virus replication compared to the mouse model. We can therefore more reliably assess the efficacy of oncolytic virotherapies, mainly oncolysis and promoter specific transgene expression. Moreover, we wanted to test potential improvements to treatment outcomes when combining oncolytic virotherapy and immune checkpoint blockade. However, there are not many commercially available research tools specific to the Syrian Hamster. This is why we developed an in vivo compatible immune checkpoint inhibitor so that we could assess the combination therapy in the Syrian hamster model. Lastly, we also wanted to validate if we could assess the efficacy of the immunotherapies using biopsies from hamsters to remove unnecessary use of animals. 2. To do this, we engrafted one PDAC tumours on the right flank of Syrian hamsters using 5 x10E+6 HapT1 cells grown in culture. When tumours reached 4-5mm in diameter, the hamsters were injected intraperitoneally with either 300ug of IgG2a control or anti-PD-L1 (clone;11B12-1). Hamsters were treated 8 times and a tumour biopsy was taken one day before the last treatment. The biopsy was immediately stored in RNA-later until extraction with RNA mini kit (Qiagen).
2023-01-30 | E-MTAB-12297 | biostudies-arrayexpress
Project description:We tested if Brd2 inhibitor ABBV-744 could reduce SARS-CoV-2 infection in Syrian Hamsters. Three days post-infection, the lungs of hamsters were harvested and subjected to RNA-seq. Infected, but untreated, hamsters showed marked up-regulation of a number of genes including ISGs when compared to uninfected controls. In contrast, hamsters treated with ABBV-744 showed a down-regulation of ISG levels, confirming ABBV-744 activity. Thus, Brd2 inhibition can decrease SARS-CoV-2 infection in Syrian Hamsters.
2021-09-02 | GSE182994 | GEO