—Vaccine Immunogenicity and Immune Response Type Assessment
The Mouse SARS-CoV-2 total IgG, IgG1 & IgG2a ELISA kits are designed for evaluating immunogenicity and type of immune response induced by the COVID-19 vaccine in mouse. The increased IgG1/ IgG2a ratio indicates the Th2 type humoral immune response, the increased IgG2a/IgG1 ratio tends to Th1 type cellular immune response. The balance of Th1/Th2 immune response will help improve the protective effect of the vaccine and avoid pathological enhancement after immunity. Increased induction of both antibody isotypes as measured by ELISA was a better correlate for vaccine efficacy than neutralization alone.
Figure 1. Detect mouse IgG1 & IgG2a serum levels by DEIASL240 and DEIASL241
The COVID-19 pandemic caused by SARS-CoV-2 has brought an unprecedented crisis, hence rapid development of effective vaccines against SARS-CoV-2 is needed. Now, multiple SARS-CoV-2 vaccine types, such as DNA-, RNA-based formulations, recombinant-subunits containing viral epitopes, adenovirus-based vectors and purified inactivated virus are developed. To fully assess the immunogenicity and safety of multiple SARS-CoV-2 vaccine antigens, the preclinical animal model testing is necessary.
In humans, the induced virus neutralization ability is the gold standard for determining vaccine efficacy. But in mouse vaccine assessment model, the detection of IgG, IgG1&IgG2a antibody titer and isotypes is a better correlate for vaccine efficacy than neutralization alone. In-depth understanding of the immune response in animal model will help to assess the protective capability, toxicity and safety of the SARS-CoV-2 vaccines.
Many clinical reports show that after infection of the host with SARS-CoV-2, the body responds by initiating a rapid immune response involving the activation of different immune cells, such as T helper cells, Th1, Th2, Th17, macrophages, dendritic cells, and neutrophils. Besides, many proinflammation cytokines related to T cell regulation, such as IL-6, TNF, IL-1, IL-2, IL-17, IFN-𝛾, G-CSF, MCP-1 (macrophage inflammatory protein 1), IP-10 (IFN-𝛾-induced protein 10), and others, were found to be significantly elevated in severe COVID-19 patients (Figure 2).
Figure 2. Major blood leukocyte, cytokine changes in mild vs. severe SARS-CoV-2 infection
It is well established that the phenotype of murine T helper (Th) lymphocytes can be defined by their profile of cytokine secretion. Thus, lymphocytes of the Th1 subset are characterized by their ability to secrete interferon gamma (IFN-𝛾) and interleukin-2 (IL-2), whereas those of the Th2 subset produce IL-4 and IL-5. In immunology, it has been widely reported that the isotope of serum antibodies can be used as an indicator of Th lymphocyte dominance, by virtue of the effects that certain cytokines have on immunoglobulin (Ig) isotype selection in B cell. For example, the Th2 cytokine IL-4 appears to promote B cells to make IgG1, and inhibits IgG2a secretion, whilst the Th1 cytokine IFN-𝛾 enhances IgG2a production but inhibits IgG1. Therefore, the parameters commonly measured in vaccine immune response research are IFN-γ as the Th1 like response, IL-4 as the Th2 like response, and IgG2a/IgG1 ratios as the Th1/Th2 deviation markers.
Th1 cells in patients with severe COVID-19 were reported to stimulate the production of IL-6 by inflammatory monocytes, which, together with Th17 cells, may directly join innate immune cells in sparking the release of proinflammatory cytokines further contributing to the cytokine storm, which is closely related to disease severity of COVID-19. Regulatory T cells (Tregs) play a critical role in dampening an excessive inflammatory response as well as in antiviral immune responses. Therefore, Tregs may be central to maintaining a balance between antiviral immunity and the harmful cytokine storm. Evaluation of Th1/Th2 can indirectly determine whether the vaccine will induce severe inflammatory response and other adverse effects.
The vaccine development effort in response to the COVID-19 pandemic is unprecedented in terms of both scale and speed. An in-depth understanding of the immune response in immune protection and immune pathology will help explain the pathogenic mechanism of SARS-CoV-2 and regulate the balance of immune status, and promote the successful development of SARS-CoV-2 vaccines. The Mouse SARS-CoV-2 total IgG, IgG1 & IgG2a ELISA kit can rapidly help you to assess the immunogenicity, toxicity and safety of the SARS-CoV-2 vaccines.
