At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19

DeMarco, Jennifer K; Severson, William; DeMarco, Daniel; Pogue, Gregory P.; Gabbard, Jon D.; Palmer, Kenneth E.

doi:10.1101/2021.02.22.432407

Cited by 2 publications

(1 citation statement)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, B cells secrete neutralizing antibodies accompanied by non-neutralizing antibodies [ 35 ], which is very important for IL-6 dynamics. Specifically, it is suggested [ 42 ] that non-neutralizing antibodies bind to macrophages and promote macrophages susceptible to the virus, and accompanied with this process, macrophages secrete a large amount of IL-6. Based on this, we propose that IL-6 production by non-neutralizing antibodies dominates the cytokine storm taking place at the later stage [ 3 ] and neglect the IL-6 produced by T cells, monocytes and infected cells [ 34 ].…”

Section: Causal Network and Mathematic Model Of The Antiviral-inflammation Responsesmentioning

confidence: 99%

Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19

Zhang

Song

et al. 2021

R. Soc. open sci.

View full text Add to dashboard Cite

Clarifying dominant factors determining the immune heterogeneity from non-survivors to survivors is crucial for developing therapeutics and vaccines against COVID-19. The main difficulty is quantitatively analysing the multi-level clinical data, including viral dynamics, immune response and tissue damages. Here, we adopt a top-down modelling approach to quantify key functional aspects and their dynamical interplay in the battle between the virus and the immune system, yielding an accurate description of real-time clinical data involving hundreds of patients for the first time. The quantification of antiviral responses gives that, compared to antibodies, T cells play a more dominant role in virus clearance, especially for mild patients (96.5%). Moreover, the anti-inflammatory responses, namely the cytokine inhibition and tissue repair rates, also positively correlate with T cell number and are significantly suppressed in non-survivors. Simulations show that the lack of T cells can lead to more significant inflammation, proposing an explanation for the monotonic increase of COVID-19 mortality with age and higher mortality for males. We propose that T cells play a crucial role in the immunity against COVID-19, which provides a new direction–improvement of T cell number for advancing current prevention and treatment.

show abstract

Section: Causal Network and Mathematic Model Of The Antiviral-inflammation Responsesmentioning

confidence: 99%

Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19

Zhang

Song

et al. 2021

R. Soc. open sci.

View full text Add to dashboard Cite

show abstract

Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice

et al. 2023

View full text Add to dashboard Cite

Background The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its “Generally Regarded as Safe” status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. Results In this study, the possible antigenic determinants of the spike (S1–1, S1–2, S1–3, and S1–4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1–1 and S1–2 groups, followed by that in the S1–3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1–1, S1–2, and S1–3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1–1, S1–2, and S1–3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. Conclusion This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.

show abstract

At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19

Cited by 2 publications

References 28 publications

Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19

Impairment of T cells' antiviral and anti-inflammation immunities may be critical to death from COVID-19

Mucosal immunization with Lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice

Contact Info

Product

Resources

About