In a recent article published in Nature Communications, researchers discuss 7DW8-5, a glycolipid that utilizes the body's non-specific immune response to quickly combat viral infections, including the coronavirus disease 2019 (COVID-19) in vivo.
Study: An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo. Image Credit: luminance studio / Shutterstock.com
Background
Despite the widespread destruction caused by the COVID-19 pandemic, there has been a massive scientific response to generate and implement countermeasures against the transmission of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For example, several prophylactic vaccines, which were developed by harnessing the power of the acquired immune system , remain highly effective against symptomatic infection.
Nevertheless, vaccine-breakthrough infections rose in frequency due to the continued spread of SARS-CoV-2 and evolution of viral variants. Thus, the development of novel preventive measures could reduce the transmission of SARS-CoV-2, such as those that utilize the host's innate immune system and facilitate quick infection control.
Natural killer T (NKT) cells, a vital component of the non-specific immune response, play a role in autoimmune diseases and cancer and protect against infections. Numerous studies demonstrated the significance of invariant NKT (iNKT) cells against viral infections like those caused by retroviruses, cytomegalovirus (CMV), influenza, and respiratory syncytial virus (RSV), as well as the function of NKT cells in adaptive immune responses against viruses.
About the study
In the current study, researchers evaluate the cluster of differentiation 1 (CD1d)-iNKT cell-dependent impact of an immunostimulatory glycolipid termed 7DW8-5 in preventing RSV, influenza virus, and SARS-CoV-2 infections in animal models. To this end, 7DW8-5 was used to stimulate the host's non-specific immune response to manage viral infections in vivo.
The efficiency of the glycolipid in blocking viral infections was tested in hamsters and mice infected with the SARS-CoV-2 Delta variant, as well as the Omicron BA.5 and BA.1 subvariants, in addition to the influenza virus and RSV. The Omicron subvariants were evaluated in wild-type mice, while the Delta variant was analyzed in keratin 18-human angiotensin-converting enzyme 2 (K18-hACE2) transgenic mice.
The mechanism of action of 7DW8-5 in blocking viral infections was assessed through various techniques, including messenger ribonucleic acid (mRNA) sequencing, single-cell RNA sequencing, and in vitro inhibition assays. Single-cell RNA sequencing and mRNA sequencing were conducted to analyze gene expression variations linked with 7DW8-5 glycolipid treatment.
Study findings
The results indicate that the 7DW8-5 glycolipid could be employed to boost the host's innate immune system to manage viral infections in vivo. Moreover, intranasal 7DW8-5 administration before viral exposure significantly prevented infection by RSV, influenza virus, as well as the SARS-CoV-2 Delta variant, and Omicron BA.5 and BA.1 subvariants in hamsters and mice. The protective antiviral impact of 7DW8-5 was both mechanism-specific and host-directed, necessitating interferon (IFN)-γ and CD1d molecules.
The mechanism of action of 7DW8-5 involves binding to CD1d on antigen-presenting cells and inducing NKT cells to release a series of chemokines and cytokines. The upregulation of genes were implicated in the non-specific immune response, particularly IFN-stimulated genes, was linked to the 7DW8-5-mediated protection against SARS-CoV-2 infection.
Additionally, 7DW8-5-mediated SARS-CoV-2 protection was observed in both humans and mice. In vitro SARS-CoV-2 infection of a human hepatocarcinoma cell line, Huh7 cells, was significantly inhibited by supernatants from CD1d-transfected Hela cells-stimulated human iNKT cell lines in the presence of 7DW8-5. However, this inhibition was eliminated following the addition of neutralizing anti-human IFN-γ antibody to the culture.
The CD1d molecule is conserved between mice and humans. Furthermore, since CD1d-transfected Hela cells-stimulated human iNKT cell lines blocked SARS-CoV-2 infection in vitro, humans may similarly benefit from the 7DW8-5-mediated SARS-CoV-2 protection established in mice.
Conclusions
The 7DW8-5 glycolipid was found to activate the non-specific immune system of the host to combat viral infections in vivo. More specifically, 7DW8-5 blocked influenza virus, RSV, and three distinct authentic SARS-CoV-2 variants infections in hamsters and mice.
In addition, 7DW8-5-mediated SARS-CoV-2 protection was linked to the upregulation of genes associated with the non-specific immune reaction. Thus, a glycolipid such as 7DW8-5 that is inexpensive to manufacture and easy to administer may reduce the transmission of SARS-Cov-2 and address future pandemics before drugs or vaccines become available.
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