Dataset Information

Distinct patterns of whole blood transcriptional responses are induced in mice following immunisation with adenoviral and poxviral vector vaccines encoding the same antigen

ABSTRACT:

Background

Viral vectors, including adenovirus (Ad) and modified vaccinia Ankara (MVA), have gained increasing attention as vaccine platforms in recent years due to their capacity to express antigens from a wide array of pathogens, their rapid induction of humoral and cellular protective immune responses, and their relatively low production costs. In particular, the chimpanzee Ad vector, ChAdOx1, has taken centre stage as a leading COVID-19 vaccine candidate. However, despite mounting data, both clinical and pre-clinical, demonstrating effective induction of adaptive immune responses, the innate immune signals that precede the protective responses that make these vectors attractive vaccine platforms remain poorly understood.

Results

In this study, a mouse immunisation model was used to evaluate whole blood gene expression changes 24 h after either a single dose or heterologous prime-boost regimen of an Ad and/or MVA vaccine. We demonstrate through comparative analysis of Ad vectors encoding different antigens that a transgene product-specific gene signature can be discerned from the vector-induced transcriptional response. Expression of genes involved in TLR2 stimulation and γδ T cell and natural killer cell activation were induced after a single dose of Ad, while MVA led to greater expression of type I interferon genes. The order of prime-boost combinations was found to influence the magnitude of the gene expression changes, with MVA/Ad eliciting greater transcriptional perturbation than Ad/MVA. Contrasting the two regimens revealed significant enrichment of epigenetic regulation pathways and augmented expression of MHC class I and II molecules associated with MVA/Ad.

Conclusion

These data demonstrate that the order in which vaccines from heterologous prime-boost regimens are administered leads to distinct transcriptional responses and may shape the immune response induced by such combinations. The characterisation of early vaccine-induce responses strengthens our understanding of viral vector vaccine mechanisms of action ahead of their characterisation in human clinical trials and are a valuable resource to inform the pre-clinical design of appropriate vaccine constructs for emerging infectious diseases.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12864-021-08061-8.

SUBMITTER: Sheerin D

PROVIDER: S-EPMC8556829 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Emergence of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak identified in late 2019 in Wuhan, China, was declared a pandemic in March 2020. High fatality rate in afflicted patients prompted scientists and physicians to develop various vaccines against the virus. While administration of millions of doses of the adenoviral vector vaccines (e.g., Oxford-AstraZeneca (ChAdOx1 nCoV-19) and Janssen/Johnson & Johnson (Ad26.COV2. S)) has helped control the disease, numerous cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia have been reported in vaccinated individuals. In this article, we aim to review the cases reported thus far and further discuss the association between the vaccine administration and subsequent cerebral thromboembolic events. Our study was performed and reported based on the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Google Scholar and Norris Medical Library databases were searched using the following terms: coronavirus disease 2019 (COVID-19) vaccines (“AstraZeneca” or “AZD1222 COVID vaccine” or “ChAdOx1 nCoV-19 COVID-19 vaccine” or “Janssen” or “Johnson & Johnson COVID vaccine” or “Ad26.COV2 COVID vaccine”), coagulopathy (“cerebral venous sinus thrombosis (CVST)” and “vaccine-induced immune thrombotic thrombocytopenia (VITT)” or “cerebral venous thrombosis (CVT)”) and thrombocytopenia. All the relevant studies within the English literature up to August 1, 2021, were included. Fourteen most recent articles reporting on 66 patients with CVST and VITT after adenoviral vector vaccination were reviewed by two independent authors. Age of the patients ranged from 18 to 60 years. The majority of cases were women (43 females versus 14 males). Platelet count was between 5 and 127 × 109/L. Above-normal D-dimer was found in 86% of the patients. A total of 68% of the patients had positive platelet factor 4 IgG assay in the absence of prior exposure to heparin. Among CVST cases following COVID vaccination, 44% succumbed to death. Early diagnosis and treatment of CVST plays a fundamental role in decreasing morbidity and mortality. Health care professional should be familiar with this rare complication post vaccination against COVID-19. Given the rarity of CVST after the COVID-19 vaccine, the benefit of vaccination outweighs the potential harm.