J&J vaccine prevents thrombosis and inflammation induced by SARS-CoV-2 in hamsters

The 2019 coronavirus disease (COVID-19) pandemic has resulted in an intense focus on vaccine development. Animal models have been used to assess the efficacy of newly developed vaccines and to define molecular and immunological correlates of protection.

To study: Ad26.COV2.S prevents the inflammatory and thrombotic pathways induced by SARS-CoV-2 in hamsters. Image Credit: pcruciatti / Shutterstock.com

The usefulness of animal models

Hamsters and rhesus macaques are the primary models used to study the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccine efficacy. The utility of these models is due to their ability to exhibit robust viral replication in the upper and lower respiratory tract when infected with SARS-CoV-2.

Proteomic and transcriptomic reports from lung tissue and hamster blood infected with SARS-CoV-2 demonstrated complement activation, upregulation of interferon (IFN) and pro-inflammatory pathways, and recruitment of macrophages and neutrophils in the lungs of infected hamsters. Taken together, these responses correlate with the presence of SARS-CoV-2 viral RNA, which supports the roles of pro-inflammatory responses in COVID-19 severity.

Thus, it is essential that COVID-19 vaccinations be tested in these models to determine whether they influence the immune and transcriptional responses of the host. In addition, these studies can also determine whether protection is provided against excessive pro-inflammatory responses.

In a recent study published on the Preprint Server bioRxiv *, the researchers performed a bulk ribonucleic acid (RNA) -seq transcriptome profile of lung tissue from vaccinated and unvaccinated hamsters four days after challenge with SARS-CoV-2. The vaccines used for this study were Ad26.COV2.S (Ad26) and S.dTM.PP.

AD26 vaccine eradicates detection of SARS-CoV-2

Analysis via RNA-Seq and transcriptomic profiling revealed that within each group of hamsters, the transcriptome profiles were homogeneous. In addition, no significant difference between groups of animals that received different doses of vaccine was observed.

In unvaccinated hamsters, RNA-Seq reads were mapped to the SARS-CoV-2 genome. A significant number of reads mapped to the SARS-CoV-2 transcripts were observed, ranging from 300 to 315,000.

However, in hamsters vaccinated S.dTM.PP, a lower number of reads was found to be mapped to SARS-CoV2 transcripts, ranging from 10 to 16,000 reads. With hamsters vaccinated with Ad26, SARS-CoV-2 readings were undetectable, with only 0 to 12 reads mapping SARS-CoV-2 transcripts.

Compared to naive animals, differences were observed in upregulation and downregulation of genes in vaccinated and unvaccinated animals by analysis of differential expression genes (DEG). Significant differences in the transcriptome profile of hamsters given the AD26 vaccine were observed compared to unvaccinated hamsters, with 3,401 genes expressed differently between the two groups. Comparatively, only 87 differentially expressed genes were detected between vaccinated SdTM.PP hamsters compared to unvaccinated hamsters.

Vaccinated hamsters were found to express downregulation of pro-inflammatory markers and increased expression of IFN receptors compared to unvaccinated animals. These results are consistent with previous work by the authors, where they found that hamsters vaccinated with the S.dMT.PP vaccine exhibited more unwanted side effects than hamsters given the Ad26 vaccine.

Ad26 vaccine attenuates IFN and inflammatory signaling pathways

A major factor contributing to the severity of illness and death is an excessive inflammatory response to SARS-CoV-2. Activation of pro-inflammatory cytokines and chemokines and IFN type I and II responses have been reported previously in lung tissue and blood from COVID-19 patients and hamsters infected with SARS-CoV-2.

The authors integrated their transcriptomic data in hamsters that had been vaccinated and compared the levels of certain pro-inflammatory pathways to naive and unvaccinated groups.

Enrichment analysis of the DEG gene set showed pathways for inflammasome, IFN signaling, and pro-inflammatory cytokine signaling, such as tumor necrosis factor (TNF), IFN-α, interleukin-1 (IL-1) and IL-6 signaling were significantly increased in unvaccinated hamsters compared to naive hamsters. Four days after infection, a direct comparison between vaccinated and unvaccinated hamsters showed a significant decrease in the activation of pro-inflammatory pathways in vaccinated S.dMT.PP compared to unvaccinated hamsters.

Pro-inflammatory cytokines and chemokines such as IL-6, IL-1α, and IL-1β have been shown to contribute to the pathogenesis of COVID-19. IL-6, IL-1α, and IL-1β were all highly expressed in unvaccinated hamsters compared to naive hamsters. The expression levels of these pro-inflammatory cytokines and chemokines were comparable between vaccinated and naive hamsters.

Implications

The author found that Ad26.COV2.S vaccination in hamsters prevented upregulation of pathological pathways induced by SARS-CoV-2. In addition, the researchers demonstrated how the transcriptomic profile of vaccinated hamsters was comparable to that of uninfected false hamsters.

Humoral and cellular immune responses have also been induced following the Ad26 vaccine. Taken together, the results of the present study provided information on potential methods of protecting the lungs against SARS-CoV-2.

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.